Copeptin concentration in cord blood in infants with early-onset sepsis, chorioamnionitis and perinatal asphyxia

PubMed Central

2011-01-01

Background Vasopressin is one of the most important physiological stress and shock hormones. Copeptin, a stable vasopressin precursor, is a promising sepsis marker in adults. In contrast, its involvement in neonatal diseases remains unknown. The aim of this study was to establish copeptin concentrations in neonates of different stress states such as sepsis, chorioamnionitis and asphyxia. Methods Copeptin cord blood concentration was determined using the BRAHMS kryptor assay. Neonates with early-onset sepsis (EOS, n = 30), chorioamnionitis (n = 33) and asphyxia (n = 25) were compared to a control group of preterm and term (n = 155) neonates. Results Median copeptin concentration in cord blood was 36 pmol/l ranging from undetectable to 5498 pmol/l (IQR 7 - 419). Copeptin cord blood concentrations were non-normally distributed and increased with gestational age (p < 0.0001). Neonates born after vaginal compared to cesarean delivery had elevated copeptin levels (p < 0.0001). Copeptin correlated strongly with umbilical artery pH (Spearman's Rho -0.50, p < 0.0001), umbilical artery base excess (Rho -0.67, p < 0.0001) and with lactate at NICU admission (Rho 0.54, p < 0.0001). No difference was found when comparing copeptin cord blood concentrations between neonates with EOS and controls (multivariate p = 0.30). The highest copeptin concentrations were found in neonates with asphyxia (median 993 pmol/l). Receiver-operating-characteristic curve analysis showed that copeptin cord blood concentrations were strongly associated with asphyxia: the area under the curve resulted at 0.91 (95%-CI 0.87-0.96, p < 0.0001). A cut-off of 400 pmol/l had a sensitivity of 92% and a specifity of 82% for asphyxia as defined in this study. Conclusions Copeptin concentrations were strongly related to factors associated with perinatal stress such as birth acidosis, asphyxia and vaginal delivery. In contrast, copeptin appears to be unsuitable for the diagnosis of EOS. PMID:21595972

Multidrug-resistant organisms in neonatal sepsis in two tertiary neonatal ICUs, Egypt.

PubMed

Awad, Hesham A; Mohamed, Maha H; Badran, Nabil F; Mohsen, Manal; Abd-Elrhman, Al-Sayed A

2016-03-01

Neonatal sepsis remains a serious problem in any neonatal intensive care unit (NICU). Bacterial organisms have developed increased resistance to commonly used antibiotics. Because not enough data are available from Egypt, the aim of the present study was to determine the causative bacteria and the level of their resistance to commonly used antibiotics in tertiary NICUs in Cairo, Egypt. A 3.5-year retrospective study was carried out at NICUs of the Children's Hospital of Ain Shams University and that of El-Hussein Hospital, Al-Azhar University, Egypt. Records of neonates were reviewed. All neonates with culture-proven sepsis were included in the study. Almost one-third of the admitted neonates (33.4%) were diagnosed as having neonatal sepsis, 32.25% of them culture-proven. Early/late onset sepsis was found in 35.4 and 64.6%, respectively. Gram-negative/gram-positive bacteria was found in 68 to 25.6%. Fungal infection was detected in 9% of the isolates. Escherichia coli was the main pathogen isolated in both early-onset sepsis (41.2%) and late-onset sepsis (24.5%). Overall, 77% of the isolates were multidrug-resistant (60% of gram-positive bacteria and 83.4% of gram-negative bacteria). Nearly 80% (79%) of mortality was caused by multidrug-resistant organisms. Gram-positive and gram-negative bacteria showed high resistance against commonly used antibiotics such as ampicillin, amoxicillin, cefotaxime, ceftriaxone, and gentamicin. There is an alarming increase in antibiotic resistance to the commonly used antibiotics. Continuous surveillance for antibiotic susceptibility is needed to ensure proper empirical therapy. Improvement of infection control practices, avoidance of irrational use of antibiotics, and revision of the protocols are mandatory in the prevention of neonatal sepsis.

Quality improvement in pediatric sepsis.

PubMed

Melendez, Elliot; Bachur, Richard

2015-06-01

Although there is abundant literature detailing the impact of quality improvement in adult sepsis, the pediatric literature is lacking. Despite consensus definitions for sepsis, which patients along the sepsis spectrum should receive aggressive management and the exact onset of sepsis ('time zero') are not clearly established. In the adult emergency department (ED), sepsis onset is defined as the time of entry into the ED; however, this definition cannot be applied to hospitalized patients or patients who evolve during their ED course. Since the time of sepsis onset will dictate the timeliness of subsequent process measures, the variable definitions in the literature make it difficult to generalize findings among prior studies. Despite the variation in defining time zero, aggressive fluid administration, timely antibiotics, and compliance with sepsis bundles have been shown to improve mortality and to reduce hospital and intensive care length of stay. In addition, early identification tools show promise in beginning to define sepsis onset and retrospective search tools may allow improved case finding of those children of concern for sepsis. Quality improvement in pediatric sepsis is evolving. As we continue to define quality measures, we must standardize the definition of sepsis onset. This definition should be applicable to any treatment venue to ensure measures can be evaluated across all settings. In addition, we must delineate which patients along the sepsis spectrum should be candidates for timely interventions and standardize other outcome measures beyond mortality.

Effect of gestational age on the epidemiology of late-onset sepsis in neonatal intensive care units - a review.

PubMed

Afonso, Elsa Da Palma; Blot, Stijn

2017-10-01

Neonatal sepsis is a major cause of morbidity and mortality. Late-onset sepsis affects a significant percentage of infants admitted to the neonatal intensive care unit (NICU). Most affected newborns are preterm or low birth weight, but late-onset sepsis also affects late preterm and term infants. Understanding how gestational age affects the epidemiology of late-onset sepsis can be of use when defining strategies for its prevention and clinical management in NICU. Areas covered: Available evidence suggests the incidence and mortality of late-onset sepsis is higher in preterm and VLBW infants, but pathogen distribution and risk exposure is similar across all infants admitted to NICU. More research is required for late-onset sepsis in late preterm and term infants admitted to NICU. There is some research insight on the impact of gut bacteria in the epidemiology of Gram-negative sepsis, which could benefit from further dedicated studies. Expert commentary: Understanding the manner in which some infants develop severe sepsis and others don't and what the long-term outcomes are is fundamental to guide management strategies. Further research should focus both on infants' characteristics and on pathogenic processes. The ultimate goal is to be able to design guidelines for prevention and management of sepsis that are adapted to a varied neonatal population.

Early sepsis, obstructive jaundice and right-sided diaphragmatic hernia in the newborn.

PubMed

García-Muñoz, F; Santana, C; Reyes, D; Wiehoff, A; López-Pinto, J M; García-Alix, A

2001-01-01

A male newborn was admitted to our Unit because of early sepsis and shock. He required antimicrobial therapy and mechanical ventilation and initially did well, although he exhibited jaundice and cholestasis. During the second week he deteriorated, with radiological opacification of the right hemithorax and pleural effusion, and did poorly in spite of antibiotical therapy and drainage of the effusion. In the third week, the X-ray suggested some bowel loops in the right hemithorax. A right-sided diaphragmatic hernia was confirmed by a CT-scan, and surgery was performed with good outcome. The association of delayed-onset right-sided CDH following early sepsis and obstructive jaundice has not been published before, and illustrates a scarcely known form of presentation of this condition.

Emergence of Antibiotic Resistance-Associated Clones Among Escherichia coli Recovered From Newborns With Early-Onset Sepsis and Meningitis in the United States, 2008–2009

PubMed Central

Weissman, Scott J.; Hansen, Nellie I.; Zaterka-Baxter, Kristen; Higgins, Rosemary D.; Stoll, Barbara J.

2016-01-01

Background Escherichia coli associated with early-onset sepsis (EOS) have historically been antibiotic-susceptible and K1-encapsulated. In the era of emerging antibiotic resistance, however, the clonal makeup of E coli associated with EOS has not been well characterized. Methods Escherichia coli isolates were collected from 28 cases of EOS and early-onset meningitis (EOM) from April 2008 through December 2009, during a parent study conducted at National Institute of Child Health and Human Development Neonatal Research Network centers from February 2006 through December 2009. Clinical and microbiologic data were collected for the parent study. We applied polymerase chain reaction- and sequence-based molecular techniques to determine clonal, virulence-associated and antibiotic resistance-associated traits of the E coli isolates. Results Among 28 E coli strains, phylogroup B2 strains predominated (68%), of which more than half were K1-encapsulated (53%). Phylogroup D strains were prominent as well (18%), but none were K1-encapsulated. Across the strain collection, the rate of ampicillin resistance was high (78%). The sole strain resistant to either extended-spectrum cephalosporins or fluoroquinolones represented ST131 H30-Rx, the multidrug-resistant subclone that has emerged worldwide in the last decade. This strain encoded extended-spectrum β-lactamase CTX-M-15 and carried an IncF plasmid of type F2:A1:B-. Conclusions In this collection of EOS/EOM-associated E coli isolates, we observed a high rate of ampicillin resistance, a low rate of fluoroquinolone resistance, and no aminoglycoside resistance, with resistance to third-generation cephalosporins appearing in only a single strain, from the worldwide emerging ST131 clone. Ongoing surveillance of antibiotic resistance among EOS isolates is warranted, to ensure that standard empiric regimens remain effective. PMID:26407251

Epidemic microclusters of blood-culture proven sepsis in very-low-birth weight infants: experience of the German Neonatal Network.

PubMed

Härtel, Christoph; Faust, Kirstin; Avenarius, Stefan; Bohnhorst, Bettina; Emeis, Michael; Gebauer, Corinna; Groneck, Peter; Heitmann, Friedhelm; Hoehn, Thomas; Hubert, Mechthild; Kribs, Angela; Küster, Helmut; Laux, Reinhard; Mögel, Michael; Müller, Dirk; Olbertz, Dirk; Roll, Claudia; Siegel, Jens; Stein, Anja; Vochem, Matthias; Weller, Ursula; von der Wense, Axel; Wieg, Christian; Wintgens, Jürgen; Hemmelmann, Claudia; Simon, Arne; Herting, Egbert; Göpel, Wolfgang

2012-01-01

We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice

Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-β-D-glucan assay, Candida score, and colonization index

PubMed Central

2011-01-01

Introduction The culture-independent serum (1→3)-β-D-glucan (BG) detection test may allow early diagnosis of invasive fungal disease, but its clinical usefulness needs to be firmly established. A prospective single-center observational study was conducted to compare the diagnostic value of BG assay, Candida score (CS), and colonization index in intensive care unit (ICU) patients at risk for Candida sepsis. Methods Of 377 patients, consecutively admitted to ICU for sepsis, 95 patients having an ICU stay of more than five days were studied. Blood specimens for fungal culture and BG measurement were obtained at the onset of clinical sepsis. For CS and colonization index calculations, surveillance cultures for Candida growth, and/or clinical data were recorded. Results Sixteen (16.8%) patients were diagnosed with proven invasive fungal infection, 14 with candidiasis (13 candidemia and 1 mediastinitis) and 2 with pulmonary aspergillosis or fusariosis. Of 14 invasive Candida-infection patients, 13 had a serum sample positive for BG, 10 had a CS value ≥3, and 7 a colonization index ≥0.5. In the 12 candidemic patients, a positive BG result was obtained 24 to 72 hrs before a culture-documented diagnosis of invasive candidiasis. The positive and negative predictive values for the BG assay were higher than those of CS and colonization index (72.2% versus 57.1% and 27.3%; and 98.7% versus 97.2% and 91.7%, respectively). Conclusions A single-point BG assay based on a blood sample drawn at the sepsis onset, alone or in combination withCS, may guide the decision to start antifungal therapy early in patients at risk for Candida infection. PMID:22018278

Sepsis in Obstetrics: Clinical Features and Early Warning Tools.

PubMed

Parfitt, Sheryl E; Bogat, Mary L; Hering, Sandra L; Ottley, Charlotte; Roth, Cheryl

Morbidity and mortality associated with sepsis has gained widespread attention on a local, state, and national level, yet, it remains a complicated disorder that can be difficult to identify in a timely manner. Sepsis in obstetric patients further complicates the diagnosis as alterations in physiology related to pregnancy can mask sepsis indicators normally seen in the general population. If early signs of sepsis go unrecognized, septic shock can develop, leading to organ dysfunction and potential death. Maternal early warning tools have been designed to assist clinicians in recognizing early indications of illness. Through use of clinical pathway-specific tools, disease processes may be detected early, subsequently benefitting patients with aggressive treatment management and intervention.This article is the second in a series of three that discuss the importance of sepsis and septic shock in pregnancy. Risk factors, causes of sepsis, signs and symptoms, and maternal early warning tools are discussed.

Emergence of Antibiotic Resistance-Associated Clones Among Escherichia coli Recovered From Newborns With Early-Onset Sepsis and Meningitis in the United States, 2008-2009.

PubMed

Weissman, Scott J; Hansen, Nellie I; Zaterka-Baxter, Kristen; Higgins, Rosemary D; Stoll, Barbara J

2016-09-01

Escherichia coli associated with early-onset sepsis (EOS) have historically been antibiotic-susceptible and K1-encapsulated. In the era of emerging antibiotic resistance, however, the clonal makeup of E coli associated with EOS has not been well characterized. Escherichia coli isolates were collected from 28 cases of EOS and early-onset meningitis (EOM) from April 2008 through December 2009, during a parent study conducted at National Institute of Child Health and Human Development Neonatal Research Network centers from February 2006 through December 2009. Clinical and microbiologic data were collected for the parent study. We applied polymerase chain reaction- and sequence-based molecular techniques to determine clonal, virulence-associated and antibiotic resistance-associated traits of the E coli isolates. Among 28 E coli strains, phylogroup B2 strains predominated (68%), of which more than half were K1-encapsulated (53%). Phylogroup D strains were prominent as well (18%), but none were K1-encapsulated. Across the strain collection, the rate of ampicillin resistance was high (78%). The sole strain resistant to either extended-spectrum cephalosporins or fluoroquinolones represented ST131 H30-Rx, the multidrug-resistant subclone that has emerged worldwide in the last decade. This strain encoded extended-spectrum β-lactamase CTX-M-15 and carried an IncF plasmid of type F2:A1:B-. In this collection of EOS/EOM-associated E coli isolates, we observed a high rate of ampicillin resistance, a low rate of fluoroquinolone resistance, and no aminoglycoside resistance, with resistance to third-generation cephalosporins appearing in only a single strain, from the worldwide emerging ST131 clone. Ongoing surveillance of antibiotic resistance among EOS isolates is warranted, to ensure that standard empiric regimens remain effective. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For

Early sepsis does not increase the risk of late sepsis in very low birth weight neonates

PubMed Central

Wynn, James L.; Hansen, Nellie I.; Das, Abhik; Cotten, C. Michael; Goldberg, Ronald N.; Sánchez, Pablo J.; Bell, Edward F.; Van Meurs, Krisa P.; Carlo, Waldemar A.; Laptook, Abbot R.; Higgins, Rosemary D.; Benjamin, Daniel K.; Stoll, Barbara J.

2012-01-01

Objective To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS). Study design Retrospective analysis of VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the NICHD Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ≤72 hr of birth (EOS) or >72 hr (LOS) and antimicrobial therapy for ≥5 days or death <5 d while receiving therapy. Regression models were used to assess risk of death or LOS by 120d and LOS by 120d among survivors to discharge or 120d, adjusting for gestational age and other covariates. Results Of 34,396 infants studied 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120d did not differ overall for infants with EOS compared with those without EOS [RR:0.99 (0.89-1.09)] but was reduced in infants born at <25wk gestation [RR:0.87 (0.76-0.99), p=0.048]. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS [RR:0.88 (0.75-1.02)], but LOS risk was shorter in infants with BW 401-750 g who had EOS [RR:0.80 (0.64-0.99), p=0.047]. Conclusions Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function. PMID:23295144

Early sepsis does not increase the risk of late sepsis in very low birth weight neonates.

PubMed

Wynn, James L; Hansen, Nellie I; Das, Abhik; Cotten, C Michael; Goldberg, Ronald N; Sánchez, Pablo J; Bell, Edward F; Van Meurs, Krisa P; Carlo, Waldemar A; Laptook, Abbot R; Higgins, Rosemary D; Benjamin, Daniel K; Stoll, Barbara J

2013-05-01

To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS). Retrospective analysis of VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the National Institute of Child Health and Human Development Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ≤ 72 hours of birth (EOS) or >72 hours (LOS) and antimicrobial therapy for ≥ 5 days or death <5 days while receiving therapy. Regression models were used to assess risk of death or LOS by 120 days and LOS by 120 days among survivors to discharge or 120 days, adjusting for gestational age and other covariates. Of 34,396 infants studied, 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120 days did not differ overall for infants with EOS compared with those without EOS [risk ratio (RR): 0.99 (0.89-1.09)] but was reduced in infants born at <25 weeks gestation [RR: 0.87 (0.76-0.99), P = .048]. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS [RR: 0.88 (0.75-1.02)], but LOS risk was reduced in infants with birth weight 401-750 g who had EOS [RR: 0.80 (0.64-0.99), P = .047]. Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function. Copyright © 2013 Mosby, Inc. All rights reserved.

Early-Onset Neonatal Sepsis: Still Room for Improvement in Procalcitonin Diagnostic Accuracy Studies

PubMed Central

Chiesa, Claudio; Pacifico, Lucia; Osborn, John F.; Bonci, Enea; Hofer, Nora; Resch, Bernhard

2015-01-01

Abstract To perform a systematic review assessing accuracy and completeness of diagnostic studies of procalcitonin (PCT) for early-onset neonatal sepsis (EONS) using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative. EONS, diagnosed during the first 3 days of life, remains a common and serious problem. Increased PCT is a potentially useful diagnostic marker of EONS, but reports in the literature are contradictory. There are several possible explanations for the divergent results including the quality of studies reporting the clinical usefulness of PCT in ruling in or ruling out EONS. We systematically reviewed PubMed, Scopus, and the Cochrane Library databases up to October 1, 2014. Studies were eligible for inclusion in our review if they provided measures of PCT accuracy for diagnosing EONS. A data extraction form based on the STARD checklist and adapted for neonates with EONS was used to appraise the quality of the reporting of included studies. We found 18 articles (1998–2014) fulfilling our eligibility criteria which were included in the final analysis. Overall, the results of our analysis showed that the quality of studies reporting diagnostic accuracy of PCT for EONS was suboptimal leaving ample room for improvement. Information on key elements of design, analysis, and interpretation of test accuracy were frequently missing. Authors should be aware of the STARD criteria before starting a study in this field. We welcome stricter adherence to this guideline. Well-reported studies with appropriate designs will provide more reliable information to guide decisions on the use and interpretations of PCT test results in the management of neonates with EONS. PMID:26222858

Implementation of a protocol proposed by the Brazilian National Health Surveillance Agency for antibiotic use in very low birth weight infants.

PubMed

Pinto, Maria Cristina F Guedes; Bueno, Arnaldo C; Vieira, Alan A

2013-01-01

To analyze the implementation of a protocol proposed by the Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária - ANVISA) to improve sepsis diagnosis in very low birth weight newborns. This was a prospective study that evaluated the implementation of a protocol involving clinical and laboratory criteria (hematologic scoring system of Rodwell and C-reactive protein serial measurements), recommended by ANVISA, to improve the diagnosis of neonatal sepsis in very low birth weight newborns. The study included all patients who were born and remained in the neonatal intensive care unit until discharge or death, and excluded those with congenital diseases. The main outcomes measured in newborns before (2006-2007) and after implementation of the protocol (2008) were the rates of early and late-onset sepsis, use of antibiotics, and mortality. Means were compared by Student's t-test and categorical variables were compared by the chi-squared test; the significance level for all tests was set at 95%. The study included 136 newborns with very low birth weight. There was no difference between groups regarding general clinical characteristics in the studied periods. There was, however, a decrease in the number of diagnoses of probable early-onset sepsis (p<0.001), use of antimicrobial regimens (p<0.001), and overall mortality and infection-related mortality (p=0.009 and p=0.049, respectively). The implementation of the protocol allowed improvement of sepsis diagnosis by reducing the diagnosis of probable early-onset sepsis, thus promoting efficient antimicrobial use in this population. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Risk factors and prognosis for neonatal sepsis in southeastern Mexico: analysis of a four-year historic cohort follow-up

PubMed Central

2012-01-01

Background Neonatal sepsis is a worldwide public health issue in which, depending on the studied population, marked variations concerning its risk and prognostic factors have been reported. The aim of this study was to assess risk and prognostic factors for neonatal sepsis prevailing at a medical unit in southeastern Mexico. Thus, we used a historic cohort design to assess the association between a series of neonates and their mothers, in addition to hospital evolution features and the risk and prognosis of neonatal sepsis (defined by Pediatric Sepsis Consensus [PSC] criteria) in 11,790 newborns consecutively admitted to a Neonatology Service in Mérida, Mexico, between 2004 and 2007. Results Sepsis was found in 514 of 11,790 (4.3 %) newborns; 387 of these cases were categorized as early-onset (<72 h) (75.3 %) and 127, as late-onset (>72 h) (24.7 %). After logistic regression, risk factors for sepsis included the following: low birth weight; prematurity; abnormal amniotic fluid; premature membrane rupture (PMR) at >24 h; respiratory complications, and the requirement of assisted ventilation, O2 Inspiration fraction (IF) >60 %, or a surgical procedure. Some of these factors were differentially associated with early- or late-onset neonatal sepsis. The overall mortality rate of sepsis was 9.5 %. A marked difference in the mortality rate was found between early- and late-onset sepsis (p >0.0001). After Cox analysis, factors associated with mortality in newborns with sepsis comprised the following: prematurity; low birth weight; low Apgar score; perinatal asphyxia, and the requirement of any invasive medical or surgical procedure. Conclusions The incidence of neonatal sepsis in southeastern Mexico was 4.3 %. A different risk and prognostic profile between early- and late-onset neonatal sepsis was found. PMID:22691696

Genome Wide Association Study of Sepsis in Extremely Premature Infants

PubMed Central

Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh; Murray, Jeffrey C.; Das, Abhik; Higgins, Rosemary D.; Carlo, Waldemar A.; Bell, Edward F.; Goldberg, Ronald N.; Schibler, Kurt; Sood, Beena G.; Stevenson, David K.; Stoll, Barbara J.; Van Meurs, Krisa P.; Johnson, Karen J.; Levy, Joshua; McDonald, Scott A.; Zaterka-Baxter, Kristin M.; Kennedy, Kathleen A.; Sánchez, Pablo J.; Duara, Shahnaz; Walsh, Michele C.; Shankaran, Seetha; Wynn, James L.; Cotten, C. Michael

2017-01-01

Objective To identify genetic variants associated with sepsis (early and late-onset) using a genome wide association (GWA) analysis in a cohort of extremely premature infants. Study Design Previously generated GWA data from the Neonatal Research Network’s anonymized genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole genome amplified DNA was genotyped for 1.2 million single nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. P values and false discovery rates were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p<10−5. Secondary analyses assessed associations of SNPs with pathogen type. Pathway analyses were also run on primary and secondary end points. Results Data from 757 extremely premature infants were included: 351 infants with sepsis and 406 infants without sepsis. No SNPs reached genome-wide significance levels (5×10−8); two SNPs in proximity to FOXC2 and FOXL1 genes achieved target levels of significance. In secondary analyses, SNPs for ELMO1, IRAK2 (Gram positive sepsis), RALA, IMMP2L (Gram negative sepsis) and PIEZO2 (fungal sepsis) met target significance levels. Pathways associated with sepsis and Gram negative sepsis included gap junctions, fibroblast growth factor receptors, regulators of cell division and Interleukin-1 associated receptor kinase 2 (p values<0.001 and FDR<20%). Conclusions No SNPs met genome-wide significance in this cohort of ELBW infants; however, areas of potential association and pathways meriting further study were identified. PMID:28283553

An Interpretable Machine Learning Model for Accurate Prediction of Sepsis in the ICU.

PubMed

Nemati, Shamim; Holder, Andre; Razmi, Fereshteh; Stanley, Matthew D; Clifford, Gari D; Buchman, Timothy G

2018-04-01

Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis. Observational cohort study. Academic medical center from January 2013 to December 2015. Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively. None. High-resolution vital signs time series and electronic medical record data were extracted. A set of 65 features (variables) were calculated on hourly basis and passed to the Artificial Intelligence Sepsis Expert algorithm to predict onset of sepsis in the proceeding T hours (where T = 12, 8, 6, or 4). Artificial Intelligence Sepsis Expert was used to predict onset of sepsis in the proceeding T hours and to produce a list of the most significant contributing factors. For the 12-, 8-, 6-, and 4-hour ahead prediction of sepsis, Artificial Intelligence Sepsis Expert achieved area under the receiver operating characteristic in the range of 0.83-0.85. Performance of the Artificial Intelligence Sepsis Expert on the development and validation cohorts was indistinguishable. Using data available in the ICU in real-time, Artificial Intelligence Sepsis Expert can accurately predict the onset of sepsis in an ICU patient 4-12 hours prior to clinical recognition. A prospective study is necessary to determine the

The Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio for Detecting Early-onset Neonatal Sepsis.

PubMed

Can, Emrah; Hamilcikan, Şahin; Can, Ceren

2018-05-01

The purpose of this study was to investigate the relationship between neonate early-onset sepsis (EOS) and the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) of term neonates. This prospective observational study was conducted with term neonates diagnosed with EOS compared with 44 healthy controls. Exclusion criteria were prematurity, postmaturity, small or large for gestational age according to week of pregnancy, preeclampsia, gestational diabetes mellitus, chorioamnionitis, congenital major anomalies, and cyanotic congenital heart disease. A total of 122 term neonates were included in the study. Of these, 78 were diagnosed with EOS and 44 were healthy controls. Tachycardia and apnea with bradycardia were the most common clinical signs of the onset of EOS in neonates in the EOS group. This group had significantly higher neutrophil counts, axillary temperatures, NLRs, PLRs, C-reactive proteins, and procalcitonin levels compared with the control group. There was a positive association between neutrophil counts, NLR, and PLR in the EOS group. An NLR of 6.76 was determined as the predictive cutoff value of neonate EOS (sensitivity 97.4%; specificity 100%; area under the receiver-operating characteristic curve 0.99; P=0.001). A PLR of 94.05 was determined as the predictive cutoff value of neonate EOS (sensitivity 97.4; specificity 100%; area under the receiver-operating characteristic curve 0.93; P=0.001). NLRs and PLRs were positively correlated with EOS in term neonates, and these ratios can be used as diagnostic adjunct tests for neonate EOS workups.

A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study.

PubMed

Amland, Robert C; Lyons, Jason J; Greene, Tracy L; Haley, James M

2015-10-01

To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients' designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. 'Suspected infection' was the established gold standard to assess clinical decision support clinimetric performance. A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying 'suspected infection' as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis.

The burden of early-onset sepsis in Emilia-Romagna (Italy): a 4-year, population-based study.

PubMed

Berardi, Alberto; Baroni, Lorenza; Bacchi Reggiani, Maria Letizia; Ambretti, Simone; Biasucci, Giacomo; Bolognesi, Serenella; Capretti, Maria Grazia; Carretto, Edoardo; Ciccia, Matilde; Fiorini, Valentina; Fortini, Cinzia; Gargano, Giancarlo; Pedna, Maria Federica; Rizzo, Vittoria; Creti, Roberta; Ferrari, Fabrizio

2016-10-01

To provide the first Italian data on pathogens causing early-onset sepsis (EOS) and their antimicrobial susceptibility, after the successfully prevention of Group B streptococcus (GBS) EOS. Retrospective area-based cohort study from Emilia-Romagna (Italy). Cases of EOS registered (from 2009 to 2012) in all gestational age neonates were reviewed. Live births (LB) numbered 146 682. Ninety neonates had EOS and 12 died (incidence rates of 0.61 and 0.08/1000 LB, respectively). EOS and mortality were the highest among neonates with a birth weight <1000 g (20.37/1000 LB and 8.49/1000 LB, respectively). The most common pathogens were GBS (n = 27, 0.18/1000 LB) and Escherichia coli (n = 19, 0.13/1000 LB). Most infants affected by E. coli EOS were born preterm (n = 13), had complications (n = 4) or died (n = 7). Among 90 isolates tested, only 3 were resistant to both first line empirical antibiotics. Multivariate logistic regression analysis showed that low gestational age, caesarean section and low platelet count at presentation were significantly associated with death or brain lesions (area under ROC curve = 0.939, H-L = 0.944, sensitivity 76.0%, specificity 90.7%). GBS slightly exceeds E. coli as a cause of EOS. However, E. coli is the prominent cause of death, complications and in most cases affects preterm neonates. Empirical antimicrobial therapy of EOS seems appropriate.

Impact of neonatal intensive care bed configuration on rates of late-onset bacterial sepsis and methicillin-resistant Staphylococcus aureus colonization

PubMed Central

Julian, Samuel; Burnham, Carey-Ann D.; Sellenriek, Patricia; Shannon, William D.; Hamvas, Aaron; Tarr, Phillip I.; Warner, Barbara B.

2016-01-01

Objectives Infections cause significant morbidity and mortality in neonatal intensive care units (NICUs). The association between nursery design and nosocomial infections has not been delineated. We hypothesized that rates of colonization by methicillin-resistant Staphylococcus aureus (MRSA), late-onset sepsis, and mortality are reduced in single-patient rooms. Design Retrospective cohort study. Setting NICU in a tertiary referral center. Methods Our NICU is organized into single-patient and open-unit rooms. Clinical datasets including bed location and microbiology results were examined over a 29-month period. Differences in outcomes between bed configurations were determined by Chi-square and Cox regression. Patients All NICU patients. Results Among 1823 patients representing 55,166 patient-days, single-patient and open-unit models had similar incidences of MRSA colonization and MRSA colonization-free survival times. Average daily census was associated with MRSA colonization rates only in single-patient rooms (hazard ratio 1.31, p=0.039), while hand hygiene compliance on room entry and exit was associated with lower colonization rates independent of bed configuration (hazard ratios 0.834 and 0.719 per 1% higher compliance, respectively). Late-onset sepsis rates were similar in single-patient and open-unit models as were sepsis-free survival and the combined outcome of sepsis or death. After controlling for demographic, clinical and unit-based variables, multivariate Cox regression demonstrated that bed configuration had no effect on MRSA colonization, late-onset sepsis, or mortality. Conclusions MRSA colonization rate was impacted by hand hygiene compliance, regardless of room configuration, while average daily census only affected infants in single-patient rooms. Single-patient rooms did not reduce the rates of MRSA colonization, late-onset sepsis or death. PMID:26108888

[Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome].

PubMed

von Schnakenburg, C; Hufnagel, M; Superti-Furga, A; Rieger-Fackeldey, E; Berner, R

2009-01-01

Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

A Novel Combination of Biomarkers to Herald the Onset of Sepsis Prior to the Manifestation of Symptoms

PubMed Central

Dolin, Hallie H.; Papadimos, Thomas J.; Stepkowski, Stanislaw; Chen, Xiaohuan; Pan, Zhixing K.

2018-01-01

ABSTRACT Sepsis, which kills over 200,000 patients and costs over $20 billion in the United States alone, presents a constant but preventable challenge in the healthcare system. Among the more challenging problems that it presents is misdiagnosis due to conflation with other inflammatory processes, as its mechanisms are identical to those of other inflammatory states. Unfortunately, current biomarker tests can only assess the severity and mortality risk of each case, whereas no single test exists that can predict sepsis prior to the onset of symptoms for the purpose of pre-emptive care and monitoring. We propose that a single test utilizing three, rather than two, biomarkers that appear most quickly in the blood and are the most specific for sepsis rather than trauma, may improve diagnostic accuracy and lead to lessened patient morbidity and mortality. Such a test would vastly improve patient outcomes and quality of life, prevent complications for sepsis survivors, and prevent hospital readmissions, saving the American healthcare system money. This review summarizes the current use of sepsis biomarkers to prognosticate morbidity and mortality, and rejects the current single-biomarker and even combination biomarker tests as non-specific and inaccurate for current patient needs/pro-inflammatory cytokines, general markers of inflammation, and proteins specific to myeloid cells (and therefore to infection) are discussed. Ultimately, the review suggests a three-biomarker test of procalcitonin (PCT), interleukin-6 (IL-6), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to diagnose sepsis before the onset of symptoms. PMID:29016484

Prevention of neonatal late-onset sepsis: a randomised controlled trial.

PubMed

Alcock, Gary; Liley, Helen G; Cooke, Lucy; Gray, Peter H

2017-04-04

Late-onset sepsis (LOS), defined as sepsis occurring after 48 h of age causes substantial mortality and morbidity in very low birth weight infants. Risk factors for LOS include immaturity, intravascular catheters, mechanical ventilation, and prolonged parenteral nutrition (PN). Little attention has been paid to studying the effects of PN administration methods. The aim of the study was to compare a bundle of measures for PN line management incorporating a strict aseptic technique with standard line management on LOS in very low birth weight infants. Infants <1500 g birth weight who required PN were randomised to either a bundle of a strict aseptic technique for line management together with single use intravascular catheter for PN or a standard technique. The primary outcome was the incidence of LOS in the first 28 days of life. Secondary outcomes were mortality, neonatal morbidities and developmental outcome at 12 months of age. There were 126 infants in the aseptic technique group and 123 in the standard technique group. Forty (31.8%) infants in the aseptic technique group and 36 (29.3%) in the standard technique group had an episode of sepsis (p = 0.77). This corresponds to incidences of 15.8 and 14.2 episodes of sepsis per 1000 patient days respectively. Subgroup analyses for infants <1000 g also revealed no difference in the rate of sepsis between the intervention and control groups. (p = 0.43). There were no significant differences in secondary outcomes and development between the groups. A bundle of measures including strict aseptic technique for parenteral nutrition line management did not result in a reduction in LOS when compared to a standard technique. There is no evidence to recommend this as routine practice. Interdisciplinary Maternal Perinatal Australasian Collaborative Trials (IMPACT) Network, TRN registration number: PT0363. Date: 06/03/2001; Australian New Zealand Clinical Trials Registry (ANZCTR), TRN registration number: ACTRN

Comparison between presepsin and procalcitonin in early diagnosis of neonatal sepsis.

PubMed

Iskandar, Agustin; Arthamin, Maimun Z; Indriana, Kristin; Anshory, Muhammad; Hur, Mina; Di Somma, Salvatore

2018-05-09

Neonatal sepsis remains worldwide one of the leading causes of morbidity and mortality in both term and preterm infants. Lower mortality rates are related to timely diagnostic evaluation and prompt initiation of empiric antibiotic therapy. Blood culture, as gold standard examination for sepsis, has several limitations for early diagnosis, so that sepsis biomarkers could play an important role in this regard. This study was aimed to compare the value of the two biomarkers presepsin and procalcitonin in early diagnosis of neonatal sepsis. This was a prospective cross-sectional study performed, in Saiful Anwar General Hospital Malang, Indonesia, in 51 neonates that fulfill the criteria of systemic inflammatory response syndrome (SIRS) with blood culture as diagnostic gold standard for sepsis. At reviewer operating characteristic (ROC) curve analyses, using a presepsin cutoff of 706,5 pg/mL, the obtained area under the curve (AUCs) were: sensitivity = 85.7%, specificity = 68.8%, positive predictive value = 85.7%, negative predictive value = 68.8%, positive likelihood ratio = 2.75, negative likelihood ratio = 0.21, and accuracy = 80.4%. On the other hand, with a procalcitonin cutoff value of 161.33 pg/mL the obtained AUCs showed: sensitivity = 68.6%, specificity = 62.5%, positive predictive value = 80%, negative predictive value = 47.6%, positive likelihood ratio = 1.83, the odds ratio negative = 0.5, and accuracy = 66.7%. In early diagnosis of neonatal sepsis, compared with procalcitonin, presepsin seems to provide better early diagnostic value with consequent possible faster therapeutical decision making and possible positive impact on outcome of neonates.

[Current aspects of the definition and diagnosis of sepsis and antibiotic resistance].

PubMed

Brunkhorst, Frank M; Gastmeier, Petra; Abu Sin, Muna

2018-05-01

Hospital mortality of patients with secondary sepsis remains high at around 40%. Because of the methodological deficiencies of the definitions used so far, valid epidemiological data on secondary sepsis that allow for national and international comparisons are lacking. Since 2016, new clinical diagnostic tools that are also suitable for sepsis screening outside of intensive care units have been available. To counteract the high mortality of nosocomial sepsis, new approaches to the early identification of at-risk patients are needed. An adequate blood culture sampling rate and a high preanalytical quality should be established as a basis for quality assurance, especially in the field of nosocomial bloodstream infections; otherwise, there is a risk of surveillance bias. Data from laboratory-based antibiotic resistance surveillance on MRSA in blood culture isolates have shown a downward trend over the last 4 years. In Gram-negative pathogens, a relatively stable resistance situation has been observed over this period for many of the pathogen-antibiotic combinations.

Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality.

PubMed

Mauri, Tommaso; Bellani, Giacomo; Patroniti, Nicolo'; Coppadoro, Andrea; Peri, Giuseppe; Cuccovillo, Ivan; Cugno, Massimo; Iapichino, Gaetano; Gattinoni, Luciano; Pesenti, Antonio; Mantovani, Alberto

2010-04-01

Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis. This study is based on a prospective trial regarding the impact of glycemic control on coagulation in sepsis. Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed. At enrollment, we recorded sepsis signs, disease severity, coagulation activation [prothrombin fragments 1 + 2 (F(1+2))] and fibrinolysis inhibition [plasminogen activator inhibitor-1 (PAI-1)]. We measured plasma PTX3 levels at enrollment, everyday until day 7, then at days 9, 11, 13, 18, 23 and 28. Mortality was recorded at day 90. Although not different on day 1, PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days (p = 0.002 by general linear model). On day 1, PTX3 levels were higher in septic shock than in severely septic patients (p = 0.029). Day 1 PTX3 was significantly correlated with platelet count (p < 0.001), SAPS II score (p = 0.006) and SOFA score (p < 0.001). Day 1 PTX3 was correlated with F(1+2) concentration and with PAI-1 activity and concentration (p < 0.05 for all). Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.

Sepsis

MedlinePlus

... its early stage, before it becomes more dangerous. Sepsis To be diagnosed with sepsis, you must exhibit ... rate higher than 20 breaths a minute Severe sepsis Your diagnosis will be upgraded to severe sepsis ...

New-Onset Heart Failure and Mortality in Hospital Survivors of Sepsis-Related Left Ventricular Dysfunction.

PubMed

Vallabhajosyula, Saraschandra; Jentzer, Jacob C; Geske, Jeffrey B; Kumar, Mukesh; Sakhuja, Ankit; Singhal, Akhil; Poterucha, Joseph T; Kashani, Kianoush; Murphy, Joseph G; Gajic, Ognjen; Kashyap, Rahul

2018-02-01

The association between new-onset left ventricular (LV) dysfunction during sepsis with long-term heart failure outcomes is lesser understood. Retrospective cohort study of all adult patients with severe sepsis and septic shock between 2007 and 2014 who underwent echocardiography within 72 h of admission to the intensive care unit. Patients with prior heart failure, LV dysfunction, and structural heart disease were excluded. LV systolic dysfunction was defined as LV ejection fraction <50% and LV diastolic dysfunction as ≥grade II. Primary composite outcome included new hospitalization for acute decompensated heart failure and all-cause mortality at 2-year follow-up. Secondary outcomes included persistent LV dysfunction, and hospital mortality and length of stay. During this 8-year period, 434 patients with 206 (48%) patients having LV dysfunction were included. The two groups had similar baseline characteristics, but those with LV dysfunction had worse function as demonstrated by worse LV ejection fraction, cardiac index, and LV diastolic dysfunction. In the 331 hospital survivors, new-onset acute decompensated heart failure hospitalization did not differ between the two cohorts (15% vs. 11%). The primary composite outcome was comparable at 2-year follow-up between the groups with and without LV dysfunction (P = 0.24). Persistent LV dysfunction was noted in 28% hospital survivors on follow-up echocardiography. Other secondary outcomes were similar between the two groups. In patients with severe sepsis and septic shock, the presence of new-onset LV dysfunction did not increase the risk of long-term adverse heart failure outcomes.

Developing the surveillance algorithm for detection of failure to recognize and treat severe sepsis.

PubMed

Harrison, Andrew M; Thongprayoon, Charat; Kashyap, Rahul; Chute, Christopher G; Gajic, Ognjen; Pickering, Brian W; Herasevich, Vitaly

2015-02-01

To develop and test an automated surveillance algorithm (sepsis "sniffer") for the detection of severe sepsis and monitoring failure to recognize and treat severe sepsis in a timely manner. We conducted an observational diagnostic performance study using independent derivation and validation cohorts from an electronic medical record database of the medical intensive care unit (ICU) of a tertiary referral center. All patients aged 18 years and older who were admitted to the medical ICU from January 1 through March 31, 2013 (N=587), were included. The criterion standard for severe sepsis/septic shock was manual review by 2 trained reviewers with a third superreviewer for cases of interobserver disagreement. Critical appraisal of false-positive and false-negative alerts, along with recursive data partitioning, was performed for algorithm optimization. An algorithm based on criteria for suspicion of infection, systemic inflammatory response syndrome, organ hypoperfusion and dysfunction, and shock had a sensitivity of 80% and a specificity of 96% when applied to the validation cohort. In order, low systolic blood pressure, systemic inflammatory response syndrome positivity, and suspicion of infection were determined through recursive data partitioning to be of greatest predictive value. Lastly, 117 alert-positive patients (68% of the 171 patients with severe sepsis) had a delay in recognition and treatment, defined as no lactate and central venous pressure measurement within 2 hours of the alert. The optimized sniffer accurately identified patients with severe sepsis that bedside clinicians failed to recognize and treat in a timely manner. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Culture-proven early-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study.

PubMed

Hammoud, Majeda S; Al-Taiar, Abdullah; Al-Abdi, Sameer Y; Bozaid, Hussain; Khan, Anwar; AlMuhairi, Laila M; Rehman, Moghis Ur

2017-02-01

To investigate the incidence and the pattern of causative organisms of culture-proven early-onset sepsis (EOS) in Arab states in the Gulf region. Five neonatal care units participated in this 2-year prospective study in Kuwait, the United Arab Emirates, and Saudi Arabia. Data were collected prospectively using a standardized data collection form. EOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants within 72h of birth, with clinical and laboratory findings consistent with infection. Out of 67 474 live births, 102 cases of EOS occurred. The overall incidence of EOS was 1.5 (95% confidence interval 1.2-1.8) per 1000 live-births, ranging from 2.64 per 1000 live-births in Kuwait to 0.40 per 1000 live-births in King Abdulaziz Hospital in Saudi Arabia. The most common causative organism of EOS was group B Streptococcus (GBS; 60.0%), followed by Escherichia coli (13%). The incidence of invasive GBS disease was 0.90 per 1000 live-births overall and ranged from 1.4 per 1000 live-births in Kuwait to 0.6 per 1000 live-births in Dubai Hospital. The incidence of EOS and the patterns of the causative organisms in the Arab states in the Gulf region are similar to those in developed countries before the era of intrapartum antibiotic prophylaxis. Efforts should be made to improve intrapartum antibiotic prophylaxis in the Arab state setting, which could avert large numbers of GBS infections. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Late-onset neonatal sepsis, risk factors and interventions: an analysis of recurrent outbreaks of Serratia marcescens, 2006-2011.

PubMed

Samuelsson, A; Isaksson, B; Hanberger, H; Olhager, E

2014-01-01

Between 2006 and 2011, 11 patients with Serratia marcescens sepsis and 47 patients colonized due to the spread of various clones were observed. These recurrent clusters brought about interventions to reduce spread between patients. To evaluate the effect of stepwise interventions to prevent S. marcescens colonization/sepsis and to analyse risk factors for late-onset sepsis (LOS). An open retrospective observational study was performed to evaluate the interventions. A retrospective case-control study was performed to analyse the risk factors for LOS. S. marcescens sepsis and colonization decreased after the stepwise adoption of hygiene interventions. Low gestational age, low birth weight, indwelling central venous or umbilical catheter, and ventilator treatment were identified as risk factors for LOS. Compliance with basic hygiene guidelines was the only intervention monitored continuously from late 2007. Compliance increased gradually to a steady high level in early 2009. There was a decrease in S. marcescens LOS, clustering after the second quarter of 2008. After the first quarter of 2009, S. marcescens colonization decreased. It was not possible to identify the specific effects of each intervention, but it is likely that an update of the hospital's antibiotic policy affected the occurrence of S. marcescens LOS. The delayed effect of interventions on S. marcescens colonization was probably due to the time it takes for new routines to have an effect, illustrated by the gradual increase in compliance with basic hygiene guidelines. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

The link between early onset drinking and early onset alcohol-impaired driving in young males.

PubMed

Zhang, Lening; Wieczorek, William F; Welte, John W

2014-05-01

Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. The present study aimed to assess this link along with potentially confounding factors. The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population-based sample of 625 males at aged 16-19. Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving.

Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study.

PubMed

Stocker, Martin; Hop, Wim C J; van Rossum, Annemarie M C

2010-12-08

Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis. The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age ≥ 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the likelihood of infection (infection unlikely, possible, probable or proven). In the Procalcitonin group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range. Co-primary outcome measures are the duration of antibiotic therapy (superiority aspect of the trial) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and/or death in the first month of life (safety of study intervention, non-inferiority aspect of the trial). The number of infants to be included equals 800 per arm. With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety, i.e. excluding a disadvantage difference larger than 2% for the experimental arm, will both be greater than 80%. Benefit of the study is a possible limitation of unnecessary

Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.

PubMed

Kangelaris, Kirsten Neudoerffer; Prakash, Arun; Liu, Kathleen D; Aouizerat, Bradley; Woodruff, Prescott G; Erle, David J; Rogers, Angela; Seeley, Eric J; Chu, Jeffrey; Liu, Tom; Osterberg-Deiss, Thomas; Zhuo, Hanjing; Matthay, Michael A; Calfee, Carolyn S

2015-06-01

The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS. Copyright © 2015 the American Physiological Society.

Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS

PubMed Central

Prakash, Arun; Liu, Kathleen D.; Aouizerat, Bradley; Woodruff, Prescott G.; Erle, David J.; Rogers, Angela; Seeley, Eric J.; Chu, Jeffrey; Liu, Tom; Osterberg-Deiss, Thomas; Zhuo, Hanjing; Matthay, Michael A.; Calfee, Carolyn S.

2015-01-01

The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS. PMID:25795726

THE LINK BETWEEN EARLY ONSET DRINKING AND EARLY ONSET ALCOHOL-IMPAIRED DRIVING IN YOUNG MALES

PubMed Central

Zhang, Lening; Wieczorek, William F.; Welte, John W.

2014-01-01

Background Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. Objectives The present study aimed to assess this link along with potentially confounding factors. Methods The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population based sample of 625 males at ages of 16–19 years old. Results Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Conclusion Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving. PMID:24766089

Early detection strategy and mortality reduction in severe sepsis.

PubMed

Westphal, Glauco Adrieno; Feijó, Janaína; Andrade, Patrícia Silva de; Trindade, Louise; Suchard, Cezar; Monteiro, Márcio Andrei Gil; Martins, Sheila Fonseca; Nunes, Fernanda; Caldeira Filho, Milton

2009-06-01

To evaluate the impact of implementing an institutional policy for detection of severe sepsis and septic shock. Study before (stage I), after (stage II) with prospective data collection in a 195 bed public hospital.. Stage I: Patients with severe sepsis or septic shock were included consecutively over 15 months and treated according to the Surviving Sepsis Campaign guidelines. Stage II: In the 10 subsequent months, patients with severe sepsis or septic shock were enrolled based on an active search for signs suggesting infection (SSI) in hospitalized patients. The two stages were compared for demographic variables, time needed for recognition of at least two signs suggesting infection (SSI-Δt), compliance to the bundles of 6 and 24 hours and mortality. We identified 124 patients with severe sepsis or septic shock, 68 in stage I and 56 in stage II. The demographic variables were similar in both stages. The Δt-SSI was 34 ± 54 hours in stage I and 7 ± 8.4 hours in stage II (p <0.001). There was no difference in compliance to the bundles. In parallel there was significant reduction of mortality rates at 28 days (54.4% versus 30%, p <0.02) and hospital (67.6% versus 41%, p <0.003). The strategy used helped to identify early risk of sepsis and resulted in decreased mortality associated with severe sepsis and septic shock.

Early- versus Late-Onset Dysthymia

PubMed Central

Sansone, Lori A.

2009-01-01

In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

Liver Dysfunction and Phosphatidylinositol-3-Kinase Signalling in Early Sepsis: Experimental Studies in Rodent Models of Peritonitis

PubMed Central

Westermann, Martin; Lambeck, Sandro; Lupp, Amelie; Rudiger, Alain; Dyson, Alex; Carré, Jane E.; Kortgen, Andreas; Krafft, Christoph; Popp, Jürgen; Sponholz, Christoph; Fuhrmann, Valentin; Hilger, Ingrid; Claus, Ralf A.; Riedemann, Niels C.; Wetzker, Reinhard; Singer, Mervyn; Trauner, Michael; Bauer, Michael

2012-01-01

Background Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests. Methods and Findings In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3Kγ gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid [TDCA]) observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59), these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87). Conclusions Liver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is

The diagnostic value of interleukin-6 and interleukin-8 for early prediction of bacteremia and sepsis in children with febrile neutropenia and cancer.

PubMed

Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

2012-03-01

Early diagnosis of sepsis in children with febrile neutropenia and cancer still remains a challenge for modern medicine because of lack of specific laboratory markers and clinical signs especially at the beginning of the infection. The objective of this study was to evaluate the ability of interleukin-6 and interleukin-8 to predict bacteremia and sepsis during the first 2 days in oncohematologic patients with febrile neutropenia. A total of 61 febrile neutropenic episodes in 37 children were studied. Serum samples were collected on day 1 and day 2 from the onset of fever and analyzed using an automated random access analyzer. Neutropenic children with febrile episodes were classified into the following 2 groups: (1) fever of unknown origin group--patients with a negative blood culture--and (2) bacteremia/sepsis group--patients with a positive blood culture or clinical sepsis. High negative predictive values were found on day 1 for interleukin-6 and interleukin-8 (89% and 82%, respectively) for exclusion of bacteremia/sepsis. These interleukins could be used as a screening tool for the rejection of sepsis or bacteremia on the first day of fever in neutropenic children with cancer.

Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

PubMed

Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

2017-10-01

Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma.

PubMed

Scott, Kate M; Von Korff, Michael; Alonso, Jordi; Angermeyer, Matthias C; Benjet, Corina; Bruffaerts, Ronny; de Girolamo, Giovanni; Haro, Josep Maria; Kessler, Ronald C; Kovess, Viviane; Ono, Yutaka; Ormel, Johan; Posada-Villa, José

2008-11-01

To investigate a) whether childhood adversity predicts adult-onset asthma; b) whether early-onset depressive/anxiety disorders predict adult-onset asthma; and c) whether childhood adversity and early-onset depressive/anxiety disorders predict adult-onset asthma independently of each other. Previous research has suggested, but not established, that childhood adversity may predict adult-onset asthma and, moreover, that the association between mental disorders and asthma may be a function of shared risk factors, such as childhood adversity. Ten cross-sectional population surveys of household-residing adults (>18 years, n = 18,303) assessed mental disorders with the Composite International Diagnostic Interview (CIDI 3.0) as part of the World Mental Health surveys. Assessment of a range of childhood family adversities was included. Asthma was ascertained by self-report of lifetime diagnosis and age of diagnosis. Survival analyses calculated hazard ratios (HRs) for risk of adult-onset (>age 20 years) asthma as a function of number and type of childhood adversities and early-onset (onset asthma with risk increasing with the number of adversities experienced (HRs = 1.49-1.71). Early-onset depressive and anxiety disorders also predicted adult-onset asthma (HRs = 1.67-2.11). Childhood adversities and early-onset depressive and anxiety disorders both predicted adult-onset asthma after mutual adjustment (HRs = 1.43-1.91). Childhood adversities and early-onset depressive/anxiety disorders independently predict adult-onset asthma, suggesting that the mental disorder-asthma relationship is not a function of a shared background of childhood adversity.

Novel hybrid technology for early diagnostics of sepsis

NASA Astrophysics Data System (ADS)

Saknite, Inga; Grabovskis, Andris; Kazune, Sigita; Rubins, Uldis; Marcinkevics, Zbignevs; Volceka, Karina; Kviesis-Kipge, Edgars; Spigulis, Janis

2017-02-01

Sepsis is a potentially fatal disease with mortality rate as high as 50% in patients with septic shock; mortality rate can increase by 7.6% per hour if appropriate treatment is not started. Internationally accepted guidelines for diagnosis of sepsis rely on vital sign monitoring and laboratory tests in order to recognize organ failure. This pilot study aims to explore the potential of hyperspectral and thermal imaging techniques to identify and quantify early alterations in skin oxygenation and perfusion induced by sepsis. The study comprises both physiological model experiments on healthy volunteers in a laboratory environment, as well as screening case series of patients with septic shock in the intensive care department. Hyperspectral imaging is used to determine one of the main characteristic visual signs of skin oxygenation abnormalities - skin mottling, whereas changes in peripheral perfusion have been visualized by thermal imaging as heterogeneous skin temperature areas. In order to mimic septic skin mottling in a reproducible way in laboratory environment, arterial occlusion provocation test was utilized on healthy volunteers. Visualization of oxygen saturation by hyperspectral imaging allows diagnosing microcirculatory alterations induced by sepsis earlier than visual assessment of mottling. Thermal images of sepsis patients in the clinic clearly reveal hotspots produced by perforating arteries, as well as cold regions of low blood supply. The results of this pilot study show that thermal imaging in combination with hyperspectral imaging allows the determination of oxygen supply and utilization in critically ill septic patients.

A quality improvement project to improve early sepsis care in the emergency department.

PubMed

Gatewood, Medley O'Keefe; Wemple, Matthew; Greco, Sheryl; Kritek, Patricia A; Durvasula, Raghu

2015-12-01

Sepsis causes substantial morbidity and mortality in hospitalised patients. Although many studies describe the use of protocols in the management of patients with severe sepsis and septic shock, few have addressed emergency department (ED) screening and management for patients initially presenting with uncomplicated sepsis (ie, patients without organ failure or hypotension). A quality improvement task force at a large, quaternary care referral hospital sought to develop a protocol focusing on early identification of patients with uncomplicated sepsis, in addition to severe sepsis and septic shock. The three-tiered intervention consisted of (1) a nurse-driven screening tool and management protocol to identify and initiate early treatment of patients with sepsis, (2) a computer-assisted screening algorithm that generated a 'Sepsis Alert' pop-up screen in the electronic medical record for treating clinical healthcare providers and (3) automated suggested sepsis-specific order sets for initial workup and resuscitation, antibiotic selection and goal-directed therapy. A before and after retrospective cohort study was undertaken to determine the intervention's impact on compliance with recommended sepsis management, including serum lactate measured in the ED, 2 L of intravenous fluid administered within 2 h of triage, antibiotics administered within 3 h of triage and blood cultures drawn before antibiotic administration. Mortality rates for patients in the ED with a sepsis-designated ICD-9 code present on admission were also analysed. Overall bundle compliance increased by 154%, from 28% at baseline to 71% in the last quarter of the study (p<0.001). Bundle, antibiotic and intravenous fluid compliance all increased significantly after launch of the sepsis initiative (eg, bundle and intravenous fluid compliance increased by 74% and 54%, respectively; p<0.001). Bundle and antibiotic compliance both showed further significant increases after implementation of suggested

Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis.

PubMed

Shane, Andi L; Stoll, Barbara J

2013-02-01

Identifying neonates with sepsis is complicated by variability in clinical presentation. The incidence of early onset sepsis (EOS) resulting from invasive group B streptococcal (GBS) infections has been notably reduced by the widespread delivery of intrapartum antibiotic prophylaxis. Rates of EOS attributable to non-GBS etiologies have remained constant, and ampicillin-resistant Escherichia coli has become more prevalent. Late-onset sepsis (LOS) attributable to gram-positive organisms including coagulase-negative Staphylococci and Staphylococcus aureus is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of LOS, especially among infants who receive broad-spectrum antimicrobial agents. Prophylactic fluconazole administration to very low-birth-weight (VLBW) neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections. Targeted fluconazole prophylaxis may be beneficial in VLBW neonates who receive care in NICUs with lower rates of invasive fungal infections. Assessment of immune function, neutrophil markers, acute phase reactants, and utilization of sepsis screening scores may contribute to the management of sepsis. Maternal decolonization, antimicrobial stewardship, early enteral feeding, and optimal infection control practices are potential practical strategies for reducing the burden of neonatal sepsis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Computer versus paper system for recognition and management of sepsis in surgical intensive care.

PubMed

Croft, Chasen A; Moore, Frederick A; Efron, Philip A; Marker, Peggy S; Gabrielli, Andrea; Westhoff, Lynn S; Lottenberg, Lawrence; Jordan, Janeen; Klink, Victoria; Sailors, R Matthew; McKinley, Bruce A

2014-02-01

A system to provide surveillance, diagnosis, and protocolized management of surgical intensive care unit (SICU) sepsis was undertaken as a performance improvement project. A system for sepsis management was implemented for SICU patients using paper followed by a computerized system. The hypothesis was that the computerized system would be associated with improved process and outcomes. A system was designed to provide early recognition and guide patient-specific management of sepsis including (1) modified early warning signs-sepsis recognition score (MEWS-SRS; summative point score of ranges of vital signs, mental status, white blood cell count; after every 4 hours) by bedside nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary tract, soft tissue, other) at bedside by physician or extender; (3) sepsis management protocol (replicable, point-of-care decisions) at bedside by nurse, physician, and extender. The system was implemented first using paper and then a computerized system. Sepsis severity was defined using standard criteria. In January to May 2012, a paper system was used to manage 77 consecutive sepsis encounters (3.9 ± 0.5 cases per week) in 65 patients (77% male; age, 53 ± 2 years). In June to December 2012, a computerized system was used to manage 132 consecutive sepsis encounters (4.4 ± 0.4 cases per week) in 119 patients (63% male; age, 58 ± 2 years). MEWS-SRS elicited 683 site assessments, and 201 had sepsis diagnosis and protocol management. The predominant site of infection was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to occur more using the computerized system (paper, 23%; computer, 35%). Hospital mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with the computerized system. A computerized sepsis management system improves care process and outcome. Early sepsis is recognized and managed with greater frequency compared with severe sepsis or septic shock. The system

Risk for late-onset blood-culture proven sepsis in very-low-birth weight infants born small for gestational age: a large multicenter study from the German Neonatal Network.

PubMed

Tröger, Birte; Göpel, Wolfgang; Faust, Kirstin; Müller, Thilo; Jorch, Gerhard; Felderhoff-Müser, Ursula; Gortner, Ludwig; Heitmann, Friedhelm; Hoehn, Thomas; Kribs, Angela; Laux, Reinhard; Roll, Claudia; Emeis, Michael; Mögel, Michael; Siegel, Jens; Vochem, Matthias; von der Wense, Axel; Wieg, Christian; Herting, Egbert; Härtel, Christoph

2014-03-01

It was the aim of this study to assess whether very-low-birth-weight (VLBW) infants born small for gestational age (SGA; birth weight less than 10th percentile) are at increased risk for late-onset sepsis. This was a prospective, multicenter study of the German Neonatal Network including VLBW infants from 23 to < 32 weeks post menstrual age born 2009-2011. Outcomes were compared between VLBW infants born SGA (birth weight less than tenth percentile according to gestational age and gender) and non-SGA infants. The main outcome measure was at least 1 episode of late-onset sepsis defined as blood-culture-confirmed clinical sepsis occurring at ≥ 72 hours of age. 5886 VLBW infants were included. In SGA infants (n = 692), an increased incidence of late-onset sepsis was noted compared with non-SGA infants (20.1% vs. 14.3 %, P < 0.001). This difference was only observed among infants with a gestational age of 27 to < 32 weeks and attributed to sepsis episodes with coagulase-negative staphylococci (12.8% vs. 8.3%, P < 0.001). Different treatment modalities (eg more frequent use of central venous lines) and longer duration of invasive therapies (parenteral nutrition, mechanical ventilation, hospitalization) may account for the increased sepsis risk with coagulase-negative staphylococci in our SGA cohort. In a multivariate logistic regression analysis, higher gestational age [per week; odds ratio (OR): 0.75, 95% confidence interval (CI): 0.72-0.78, P< 0.0001], treatment with antenatal steroids (OR: 0.7, 95% CI: 0.53-0.92, P = 0.01), German descendance (OR: 0.76, 95% CI: 0.63-0.91, P = 0.003) and prophylaxis with glycopeptide antibiotics (OR: 0.64, 95% CI: 0.47-0.87, P = 0.005) were shown to be protective against late-onset sepsis. In contrast, longer duration of parenteral nutrition (per day; OR: 1.016, 95% CI: 1.011-1.021, P < 0.0001) and SGA were found to be risk factors (OR: 1.31, 95% CI: 1.02-1.68, P= 0.03). SGA contributes to the risk of late-onset sepsis in VLBW

Incidence of fever in labor and risk of neonatal sepsis.

PubMed

Towers, Craig V; Yates, Angela; Zite, Nikki; Smith, Casey; Chernicky, Lindsey; Howard, Bobby

2017-06-01

The current recommendation regarding the management of a term newborn delivered of a mother with an intrapartum fever or a diagnosis of clinical chorioamnionitis is that the neonate should have baseline laboratory work drawn along with blood cultures and be universally treated with antibiotics until culture results return. These guidelines report that the rate of intrapartum fever is about 3%; however, a few large studies suggest that the rate is higher at about 7%. We sought to prospectively evaluate the rate of fever during labor in a large number of deliveries and determine the rate of early-onset neonatal sepsis in newborns delivered from mothers with an intrapartum fever compared with newborns delivered from mothers without intrapartum fever. This was a prospective cohort study of all temperatures obtained in women in labor from Jan. 1, 2011, through June 30, 2014. Every patient with a fever of ≥38°C at ≥36 weeks' gestation was evaluated for gestational age, parity, spontaneous or induced labor, group B streptococcus status, regional anesthesia, mode of delivery, treatment with intrapartum antibiotics, and whether a clinical diagnosis of chorioamnionitis was made by the managing physician. Neonates were assessed for blood culture results, neonatal intensive care unit admission, length of stay, and any major newborn complications. Statistical analysis involved χ 2 , Fisher exact, and Student t test. A total of 412 patients (6.8%; 95% confidence interval, 6.2-7.5%) developed a fever in 6057 deliveries at ≥36 weeks' gestation. No cases of maternal sepsis occurred. Of the 417 newborns (5 sets of twins), only 1 (0.24%; 95% confidence interval, 0.01-1.3%) developed early-onset neonatal sepsis with a positive blood culture for Escherichia coli. There were 4 cases (0.07%; 95% confidence interval, 0.02-0.18%) of early-onset neonatal sepsis in the 5697 newborns (52 sets of twins) delivered from mothers who were not febrile and this difference was not significant

Does maternal intrapartum antibiotic treatment prolong the incubation time required for blood cultures to become positive for infants with early-onset sepsis?

PubMed

Sarkar, Siddhartha Sean; Bhagat, Indira; Bhatt-Mehta, Varsha; Sarkar, Subrata

2015-03-01

We hypothesized that maternal intrapartum antibiotic treatment delays the growth of the organism in the blood culture obtained during the work-up for infants with suspected early-onset sepsis (EOS). Single center, retrospective review of infants with blood culture-proven EOS over 13.5 years period. EOS was defined by isolation of a pathogen from blood culture obtained within 72 hours of birth and antibiotic treatment for  ≥ 5 days. Among 81 infants with positive blood cultures, 38 were deemed to have EOS and 43 were deemed contaminants. The organisms grown were as follows: Escherichia coli in 17 infants, Group B streptococcus in 10 infants, and others in 11 infants. Overall, 17 infants with EOS did not receive intrapartum antibiotics and had blood cultures drawn for being symptomatic after birth. The other 21 infants who received intrapartum antibiotics had blood culture drawn primarily for maternal chorioamnionitis. The median (interquartile range [IQR]) incubation time to blood culture positivity was not different in infants who received intrapartum antibiotics compared with infants who did not (19.6 hours, IQR 16-28 hours vs. 19.5 hours, IQR 17.2-21.6 hours, p = 0.7489). Maternal intrapartum antibiotic treatment did not delay the time to blood culture positivity in infants with EOS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis

PubMed Central

Wandro, Stephen; Osborne, Stephanie; Enriquez, Claudia; Bixby, Christine; Arrieta, Antonio

2018-01-01

ABSTRACT The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage. IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy

The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis.

PubMed

Wandro, Stephen; Osborne, Stephanie; Enriquez, Claudia; Bixby, Christine; Arrieta, Antonio; Whiteson, Katrine

2018-06-27

The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae , Enterococcus , and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R 2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R 2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage. IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term

Early- versus Late-Onset Systemic Sclerosis

PubMed Central

Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

2014-01-01

Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children - a data-driven approach using machine-learning algorithms.

PubMed

Lamping, Florian; Jack, Thomas; Rübsamen, Nicole; Sasse, Michael; Beerbaum, Philipp; Mikolajczyk, Rafael T; Boehne, Martin; Karch, André

2018-03-15

Since early antimicrobial therapy is mandatory in septic patients, immediate diagnosis and distinction from non-infectious SIRS is essential but hampered by the similarity of symptoms between both entities. We aimed to develop a diagnostic model for differentiation of sepsis and non-infectious SIRS in critically ill children based on routinely available parameters (baseline characteristics, clinical/laboratory parameters, technical/medical support). This is a secondary analysis of a randomized controlled trial conducted at a German tertiary-care pediatric intensive care unit (PICU). Two hundred thirty-eight cases of non-infectious SIRS and 58 cases of sepsis (as defined by IPSCC criteria) were included. We applied a Random Forest approach to identify the best set of predictors out of 44 variables measured at the day of onset of the disease. The developed diagnostic model was validated in a temporal split-sample approach. A model including four clinical (length of PICU stay until onset of non-infectious SIRS/sepsis, central line, core temperature, number of non-infectious SIRS/sepsis episodes prior to diagnosis) and four laboratory parameters (interleukin-6, platelet count, procalcitonin, CRP) was identified in the training dataset. Validation in the test dataset revealed an AUC of 0.78 (95% CI: 0.70-0.87). Our model was superior to previously proposed biomarkers such as CRP, interleukin-6, procalcitonin or a combination of CRP and procalcitonin (maximum AUC = 0.63; 95% CI: 0.52-0.74). When aiming at a complete identification of sepsis cases (100%; 95% CI: 87-100%), 28% (95% CI: 20-38%) of non-infectious SIRS cases were assorted correctly. Our approach allows early recognition of sepsis with an accuracy superior to previously described biomarkers, and could potentially reduce antibiotic use by 30% in non-infectious SIRS cases. External validation studies are necessary to confirm the generalizability of our approach across populations and treatment practices

Early decreased neutrophil responsiveness is related to late onset sepsis in multitrauma patients: An international cohort study.

PubMed

Groeneveld, Kathelijne M; Koenderman, Leo; Warren, Brian L; Jol, Saskia; Leenen, Luke P H; Hietbrink, Falco

2017-01-01

Severe trauma can lead to the development of infectious complications after several days, such as sepsis. Early identification of patients at risk will aid anticipating these complications. The aim of this study was to test the relation between the acute (<24 hours) inflammatory response after injury measured by neutrophil responsiveness and the late (>5 days) development of septic complications and validate this in different trauma populations. Two prospective, observational, cohort series in the Netherlands and South Africa, consisting of severely injured trauma patients. Neutrophil responsiveness by fMLF-induced active FcγRII was measured in whole blood flowcytometry, as read out for the systemic immune response within hours after trauma. Sepsis was scored daily. Ten of the 36 included Dutch patients developed septic shock. In patients with septic shock, neutrophils showed a lower expression of fMLF-induced active FcγRII immediately after trauma when compared to patients without septic shock (P = 0.001). In South Africa 11 of 73 included patients developed septic shock. Again neutrophils showed lower expression of fMLF induced active FcγRII (P = 0.001). In the combined cohort, all patients who developed septic shock demonstrated a decreased neutrophil responsiveness. Low responsiveness of neutrophils for the innate stimulus fMLF immediately after trauma preceded the development of septic shock during admission by almost a week and did not depend on a geographical/racial background, hospital protocols and health care facilities. Decreased neutrophil responsiveness appears to be a prerequisite for septic shock after trauma. This might enable anticipation of this severe complication in trauma patients.

Study of Umbilical Cord Blood Culture in Diagnosis of Early-onset Sepsis Among Newborns with High-risk Factors.

PubMed

Kalathia, Mitul Babubhai; Shingala, Prakash Ashokbhai; Parmar, Parin Niranjanbhai; Parikh, Yogesh Narenedrabhai; Kalathia, Ila Mitulkumar

2013-10-01

Blood culture is gold standard for diagnosis of neonatal sepsis. Low sensitivity of blood culture is usually due to small volume of blood sample, intrapartum antibiotics, and antibiotics given to newborn before sampling. We evaluated use of Umbilical cord blood culture (UCBC) in diagnosis of neonatal sepsis as compared to peripheral venous blood culture. This study was done in tertiary care teaching hospital during May-June 2012. A total of 45 newborns with presence of two or more risk factors of sepsis were included. Blood sample from placental end of umbilical cord was collected and cultured. Primary outcome was diagnosis of neonatal sepsis by use of umbilical cord blood sample as compared with venous blood sample. Secondary outcome was to compare organisms identified by UCBC and venous blood culture. Sensitivity, specificity, positive and negative predictive values of UCBC were calculated. A total of 24.44% (11 out of 45) high-risk newborns had positive UCBC. A total of 17.8% (8 out of 45) newborns had positive blood culture report. Organisms grown in UCBC were Pseudomonas (45%, 5 out of 11), Acinetobacter (27.27%, 3 out of 11), Escherichia coli (18.18%, 2 out of 11), and Klebsiella (9%, 1 out of 11). UCBC is a good method for diagnosis of neonatal sepsis among high-risk newborns as compared to venous blood culture with a sensitivity of 80% and specificity of 91.43%. Organisms grown are comparable to blood culture samples.

[Early detection on the onset of scarlet fever epidemics in Beijing, using the Cumulative Sum].

PubMed

Li, Jing; Yang, Peng; Wu, Shuang-sheng; Wang, Xiao-li; Liu, Shuang; Wang, Quan-yi

2013-05-01

Based on data related to scarlet fever which was collected from the Disease Surveillance Information Reporting System in Beijing from 2005 to 2011, to explore the efficiency of Cumulative Sum (CUSUM) in detecting the onset of scarlet fever epidemics. Models as C1-MILD (C1), C2-MEDIUM (C2) and C3-ULTRA (C3) were used. Tools for evaluation as Youden's index and detection time were calculated to optimize the parameters and optimal model. Data on 2011 scarlet fever surveillance was used to verify the efficacy of these models. C1 (k = 0.5, H = 2σ), C2 (k = 0.7, H = 2σ), C3 (k = 1.1, H = 2σ) appeared to be the optimal parameters among these models. Youden's index of C1 was 83.0% and detection time being 0.64 weeks, Youden's index of C2 was 85.4% and detection time being 1.27 weeks, Youden's index of C1 was 85.1% and detection time being 1.36 weeks. Among the three early warning detection models, C1 had the highest efficacy. Three models all triggered the signals within 4 weeks after the onset of scarlet fever epidemics. The early warning detection model of CUSUM could be used to detect the onset of scarlet fever epidemics, with good efficacy.

Evaluation of a real-time PCR assay for detection and quantification of bacterial DNA directly in blood of preterm neonates with suspected late-onset sepsis.

PubMed

van den Brand, Marre; van den Dungen, Frank A M; Bos, Martine P; van Weissenbruch, Mirjam M; van Furth, A Marceline; de Lange, Annemieke; Rubenjan, Anna; Peters, Remco P H; Savelkoul, Paul H M

2018-04-22

Rapid and accurate diagnosis of neonatal sepsis is highly warranted because of high associated morbidity and mortality. The aim of this study was to evaluate the performance of a novel multiplex PCR assay for diagnosis of late-onset sepsis and to investigate the value of bacterial DNA load (BDL) determination as a measure of infection severity. This cross-sectional study was conducted in a neonatal intensive care unit. Preterm and/or very low birth weight infants suspected for late-onset sepsis were included. Upon suspicion of sepsis, a whole blood sample was drawn for multiplex PCR to detect the eight most common bacteria causing neonatal sepsis, as well as for blood culture. BDL was determined in episodes with a positive multiplex PCR. In total, 91 episodes of suspected sepsis were investigated, and PCR was positive in 53 (58%) and blood culture in 60 (66%) episodes, yielding no significant difference in detection rate (p = 0.17). Multiplex PCR showed a sensitivity of 77%, specificity of 81%, positive predictive value of 87%, and negative predictive value of 68% compared with blood culture. Episodes with discordant results of PCR and blood culture included mainly detection of coagulase-negative staphylococci (CoNS). C-reactive protein (CRP) level and immature to total neutrophil (I/T) ratio were lower in these episodes, indicating less severe disease or even contamination. Median BDL was high (4.1 log 10 cfu Eq/ml) with a wide range, and was it higher in episodes with a positive blood culture than in those with a negative blood culture (4.5 versus 2.5 log 10 cfu Eq/ml; p < 0.0001). For CoNS infection episodes BDL and CRP were positively associated (p = 0.004), and for Staphylococcus aureus infection episodes there was a positive association between BDL and I/T ratio (p = 0.049). Multiplex PCR provides a powerful assay to enhance rapid identification of the causative pathogen in late-onset sepsis. BDL measurement may be a useful indicator of severity of infection.

Impact of an electronic sepsis initiative on antibiotic use and health care facility-onset Clostridium difficile infection rates.

PubMed

Hiensch, Robert; Poeran, Jashvant; Saunders-Hao, Patricia; Adams, Victoria; Powell, Charles A; Glasser, Allison; Mazumdar, Madhu; Patel, Gopi

2017-10-01

Although integrated, electronic sepsis screening and treatment protocols are thought to improve patient outcomes, less is known about their unintended consequences. We aimed to determine if the introduction of a sepsis initiative coincided with increases in broad-spectrum antibiotic use and health care facility-onset (HCFO) Clostridium difficile infection (CDI) rates. We used interrupted time series data from a large, tertiary, urban academic medical center including all adult inpatients on 4 medicine wards (June 2011-July 2014). The main exposure was implementation of the sepsis screening program; the main outcomes were the use of broad-spectrum antibiotics (including 3 that were part of an order set designed for the sepsis initiative) and HCFO CDI rates. Segmented regression analyses compared outcomes in 3 time segments: before (11 months), during (14 months), and after (12 months) implementation of a sepsis initiative. Antibiotic use and HFCO CDI rates increased during the period of implementation and the period after implementation compared with baseline; these increases were highest in the period after implementation (level change, 50.4 days of therapy per 1,000 patient days for overall antibiotic use and 10.8 HCFO CDIs per 10,000 patient days; P < .05). Remarkably, the main drivers of overall antibiotic use were not those included in the sepsis order set. The implementation of an electronic sepsis screening and treatment protocol coincided with increased broad-spectrum antibiotic use and HCFO CDIs. Because these protocols are increasingly used, further study of their unintended consequences is warranted. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Hippocampal Morphology and Distinguishing Late-Onset From Early-Onset Elderly Depression

PubMed Central

Ballmaier, Martina; Narr, Katherine L.; Toga, Arthur W.; Elderkin-Thompson, Virginia; Thompson, Paul M.; Hamilton, Liberty; Haroon, Ebrahim; Pham, Daniel; Heinz, Andreas; Kumar, Anand

2010-01-01

Objective Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whether these changes are regionally specific. This study used three-dimensional mapping techniques to identify regional hippocampal abnormalities in early- and late-onset depression. Neuropsychological correlates of hippocampal morphology were also investigated. Method With high-resolution magnetic resonance imaging, hippocampal morphology was compared among elderly patients with early- (N=24) and late-onset (N=22) depression and comparison subjects (N=34). Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual’s hippocampal surface model, between groups. Results Hippocampal volumes differed between depressed patients and comparison subjects but not between patients with early- and late-onset depression. However, statistical mapping results showed that regional surface contractions were significantly pronounced in late-compared to early-onset depression in the anterior of the subiculum and lateral posterior of the CA1 subfield in the left hemisphere. Significant shape differences were observed bilaterally in anterior CA1–CA3 subfields and the subiculum in patients in relation to comparison subjects. These results were similar when each disease group was separately compared to comparison subjects. Hippocampal surface contractions significantly correlated with memory measures among late- but not early-onset depressed patients or comparison subjects. Conclusions More pronounced regional volume deficits and their associations with memory in late-onset depression may suggest that these patients are more likely to develop cognitive impairment over time than individuals with early-onset depression. Mapping regional hippocampal abnormalities and their cognitive correlates may help guide research in defining risk profiles and treatment strategies. PMID:17986679

Regulators of Intestinal Epithelial Migration in Sepsis.

PubMed

Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

2018-02-08

The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

Adverse Housing Conditions and Early-Onset Delinquency.

PubMed

Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

2017-09-01

Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

Sepsis

PubMed Central

Karnatovskaia, Lioudmila V.; Festic, Emir

2012-01-01

Sepsis represents a major challenge in medicine. It begins as a systemic response to infection that can affect virtually any organ system, including the central and peripheral nervous systems. Akin to management of stroke, early recognition and treatment of sepsis are just as crucial to a successful outcome. Sepsis can precipitate myasthenic crisis and lead to encephalopathy and critical illness neuropathy. Stroke and traumatic brain injury can predispose a patient to develop sepsis, whereas Guillain-Barré syndrome is similarly not uncommon following infection. This review article will first describe the essential principles of sepsis recognition, pathophysiology, and management and will then briefly cover the neurologic aspects associated with sepsis. Vigilant awareness of the clinical features of sepsis and timeliness of intervention can help clinicians prevent progression of this disease to a multisystem organ failure, which can be difficult to reverse even after the original source of infection is under control. PMID:23983879

The impact of hospital-onset Clostridium difficile infection on outcomes of hospitalized patients with sepsis.

PubMed

Lagu, Tara; Stefan, Mihaela S; Haessler, Sarah; Higgins, Thomas L; Rothberg, Michael B; Nathanson, Brian H; Hannon, Nicholas S; Steingrub, Jay S; Lindenauer, Peter K

2014-07-01

To examine the impact of hospital-onset Clostridium difficile infection (HOCDI) on the outcomes of patients with sepsis. Most prior studies that have addressed this issue lacked adequate matching to controls, suffered from small sample size, or failed to consider time to infection. Retrospective cohort study. We identified adults with a principal or secondary diagnosis of sepsis who received care at 1 of the institutions that participated in a large multihospital database between July 1, 2004 and December 31, 2010. Among eligible patients with sepsis, we identified patients who developed HOCDI during their hospital stay. We used propensity matching and date of diagnosis to match cases to patients without Clostridium difficile infections and compared outcomes between the 2 groups. Of 218,915 sepsis patients, 2368 (1.08%) developed HOCDI. Unadjusted in-hospital mortality was significantly higher in HOCDI patients than controls (25% vs 10%, P < 0.001). After multivariate adjustment, in-hospital mortality rate was 24% in cases vs. 15% in controls. In an analysis limited to survivors, adjusted length of stay (LOS) among cases with Clostridium difficile infections was 5.1 days longer than controls (95% confidence interval: 4.4-5.8) and the median-adjusted cost increase was $4916 (P < 0.001). After rigorous adjustment for time to diagnosis and presenting severity, hospital-acquired Clostridium difficile infection was associated with increased mortality, LOS, and cost. Our results can be used to assess the cost-effectiveness of prevention programs and suggest that efforts directed toward high-risk patient populations are needed. © 2014 Society of Hospital Medicine.

Early versus late pre-intensive care unit admission broad spectrum antibiotics for severe sepsis in adults.

PubMed

Siddiqui, Shahla; Razzak, Junaid

2010-10-06

Severe sepsis and septic shock have recently emerged as particularly acute and lethal challenges amongst critically ill patients presenting to the emergency department (ED). There are no existing data on the current practices of management of patients with severe sepsis comparing early versus late administration of appropriate broad spectrum antibiotics as part of the early goal-directed therapy that is commenced in the first few hours of presentation. To assess the difference in outcomes with early compared to late administration of antibiotics in patients with severe sepsis in the pre-intensive care unit (ICU) admission period. We defined early as within one hour of presentation to the ED. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2009); MEDLINE (1990 to February 2010); EMBASE (1990 to February 2010); and ISI web of Science (February 2010). We also searched for relevant ongoing trials in specific websites such as www.controlled-trials.com; www.clinicalstudyresults.org; and www.update-software.com. We searched the reference lists of articles. There were no constraints based on language or publication status. We planned to include randomized controlled trials of early versus late broad spectrum antibiotics in adult patients with severe sepsis in the ED, prior to admission to the intensive care unit. Two authors independently assessed articles for inclusion. We found no studies that satisfied the inclusion criteria. Based on this review we are unable to make a recommendation on the early or late use of broad spectrum antibiotics in adult patients with severe sepsis in the ED pre-ICU admission. There is a need to do large prospective double blinded randomized controlled trials on the efficacy of early (within one hour) versus late broad spectrum antibiotics in adult severe sepsis patients. Since it makes sense to start antibiotics as soon as possible in this group of seriously ill patients, administering

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

PubMed

Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

2017-03-01

To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

PubMed

Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

2017-03-01

To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

[Group B streptococcal early-onset neonatal sepsis in the area of Barcelona (2004-2010). Analysis of missed opportunities for prevention].

PubMed

Giménez, Montserrat; Sanfeliu, Isabel; Sierra, Montserrat; Dopico, Eva; Juncosa, Teresa; Andreu, Antonia; Lite, Josep; Guardià, Cèlia; Sánchez, Ferran; Bosch, Jordi

2015-01-01

To study the evolution of the incidence of early-onset neonatal sepsis (EOS) by Streptococcus agalactiae in the area of Barcelona and to analyze failure of compliance with the prevention protocol. A retrospective review was carried out on EOS cases in 8 Health-Care Centers in the Barcelona area between 2004 and 2010. Forty-nine newborns from 48 mothers were diagnosed with EOS. The incidence was 0.29‰ living newborns (0.18-0.47‰), with no significant differences in the fluctuations along the 7 years. The mortality rate was 8.16%. In 68.5% cases the maternal colonization studies were negative, and in 21% these studies were not performed. No risk factors were detected in 58.3% of pregnant women, and 22.9% of births were premature. In 58% of cases intra-partum antibiotic prophylaxis was not administered because it was not indicated, and in 42% due to failure to follow the protocol (3 strains were resistant to erythromycin). Resistance to clindamycin was 33.3%. The Streptococcus agalactiae serotypes more frequently isolated were iii, v, and ia. No significant changes were detected in the incidence of Streptococcus agalactiae EOS in the 7 years of the study. The increased sensitivity of screening methods with the use of molecular techniques, the performance of susceptibility testing of strains isolated from pregnant women, and the improvement of communication between Health-Care Centers, can contribute to a better implementation of the protocol, as well as to reduce the incidence of EOS. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Development of metabolic and inflammatory mediator biomarker phenotyping for early diagnosis and triage of pediatric sepsis.

PubMed

Mickiewicz, Beata; Thompson, Graham C; Blackwood, Jaime; Jenne, Craig N; Winston, Brent W; Vogel, Hans J; Joffe, Ari R

2015-09-09

The first steps in goal-directed therapy for sepsis are early diagnosis followed by appropriate triage. These steps are usually left to the physician's judgment, as there is no accepted biomarker available. We aimed to determine biomarker phenotypes that differentiate children with sepsis who require intensive care from those who do not. We conducted a prospective, observational nested cohort study at two pediatric intensive care units (PICUs) and one pediatric emergency department (ED). Children ages 2-17 years presenting to the PICU or ED with sepsis or presenting for procedural sedation to the ED were enrolled. We used the judgment of regional pediatric ED and PICU attending physicians as the standard to determine triage location (PICU or ED). We performed metabolic and inflammatory protein mediator profiling with serum and plasma samples, respectively, collected upon presentation, followed by multivariate statistical analysis. Ninety-four PICU sepsis, 81 ED sepsis, and 63 ED control patients were included. Metabolomic profiling revealed clear separation of groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.89, area under the receiver operating characteristic curve (AUROC) of 0.96 (standard deviation [SD] 0.01), and predictive ability (Q(2)) of 0.60. Protein mediator profiling also showed clear separation of the groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.78 and AUROC of 0.88 (SD 0.03). Combining metabolomic and protein mediator profiling improved the model (Q(2) =0.62), differentiating PICU sepsis from ED sepsis with accuracy of 0.87 and AUROC of 0.95 (SD 0.01). Separation of PICU sepsis or ED sepsis from ED controls was even more accurate. Prespecified age subgroups (2-5 years old and 6-17 years old) improved model accuracy minimally. Seventeen metabolites or protein mediators accounted for separation of PICU sepsis and ED sepsis with 95% confidence. In children ages 2-17 years, combining metabolomic and

A proposed Primary Health Early Warning Score (PHEWS) with emphasis on early detection of sepsis in the elderly.

PubMed

Anderson, Ian

2016-03-01

There are several secondary care early warning scores which alert for severe illness including sepsis. None are specifically adjusted for primary care. A Primary Health Early Warning Score (PHEWS) is proposed which incorporates practical parameters from both secondary and primary care.

Clinical outcome of critically ill patients with thrombocytopenia and hypophosphatemia in the early stage of sepsis.

PubMed

Brotfain, Evgeni; Schwartz, Andrei; Boniel, Avi; Koyfman, Leonid; Boyko, Matthew; Kutz, Ruslan; Klein, Moti

2016-01-01

Hypophosphatemia and thrombocytopenia may both be independent risk factors for the development of multiple organ failure and correlate well with the severity of sepsis. In the present study we wanted to analyze the potential clinical role and prognostic significance of both early hypophosphatemia and thrombocytopenia on clinical outcomes of critically ill ICU patients with severe sepsis. We analyzed the clinical data, including the outcome of critically ill ICU patients with severe sepsis who presented during a 5 year period with early hypophosphatemia and thrombocytopenia.This study was retrospective and single centre. All clinical and laboratory data was collected from the patients' ICU and hospital electronic records. All laboratory measurements were done on admission and during the ICU stay. The included patients were distributed into one of three study groups based on the presence of hypophosphatemia and/or thrombocytopenia during the first 24 hours of admission to the ICU: group 1 - early hypophosphatemia; group 2 - early hypophosphatemia and thrombocytopenia and group 3 - early thrombocytopenia. The ICU mortality rate was significantly higher in groups 2 and 3 (25.9% and 22% vs. 9.3%, respectively, P = 0.034). An APACHE II > 27, a TISS > 25 following the first 24 hours of ICU stay , an age higher than 70, male gender and total parenteral nutrition were independent predictors of ICU and hospital mortality in this study population. It may be considered that hypophosphatemia and thrombocytopenia in the early stage of sepsis, even when severe and coexisting, reflect the degree of initial illness severity of sepsis. However, further investigations need to be done for a better understanding of the potential clinical role of these features in the septic critically ill population.

Early plasma monocyte chemoattractant protein 1 predicts the development of sepsis in trauma patients: A prospective observational study.

PubMed

Wang, Yuchang; Liu, Qinxin; Liu, Tao; Zheng, Qiang; Xu, Xi'e; Liu, Xinghua; Gao, Wei; Li, Zhanfei; Bai, Xiangjun

2018-04-01

Monocyte chemoattractant protein 1 (MCP-1) is an initiating cytokine of the inflammatory cascade. Extracellular MCP-1 exhibits pro-inflammatory characteristic and plays a central pathogenic role in critical illness. The purpose of the study was to identify the association between plasma MCP-1 levels and the development of sepsis after severe trauma.The plasma levels of MCP-1 in severe trauma patients were measured by a quantitative enzyme-linked immune sorbent assay and the dynamic release patterns were recorded at three time points during seven days post-trauma. The related factors of prognosis were compared between sepsis and non-sepsis groups and analyzed using multivariate logistic regression analysis. We also used receiver operating characteristic (ROC) curves to assess the values of different variables in predicting sepsis.A total of 72 patients who met criteria indicative of severe trauma (72.22% of male; mean age, 49.40 ± 14.29 years) were enrolled. Plasma MCP-1 concentrations significantly increased on post-trauma day 1 and that this increase was significantly correlated with the Injury Severity Score (ISS) and interleukin-6 (IL-6). Multivariate logistic regression analysis showed that early MCP-1, ISS, and IL-6 were independent risk factors for sepsis in severe trauma patients. Incorporation of the early MCP-1 into the ISS can increase the discriminative performance for predicting development of sepsis.Early plasma MCP-1 concentrations can be used to assess the severity of trauma and is correlated with the development of sepsis after severe trauma. The addition of the early MCP-1 levels to the ISS significantly improves its ability to predict development of sepsis.

Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity

PubMed Central

Rivers, Emanuel P.; McIntyre, Lauralyn; Morro, David C.; Rivers, Kandis K.

2005-01-01

The pathogenic, diagnostic and therapeutic landscape of sepsis is no longer confined to the intensive care unit: many patients from other portals of entry to care, both outside and within the hospital, progress to severe disease. Approaches that have led to improved outcomes with other diseases (e.g., acute myocardial infarction, stroke and trauma) can now be similarly applied to sepsis. Improved understanding of the pathogenesis of severe sepsis and septic shock has led to the development of new therapies that place importance on early identification and aggressive management. This review emphasizes approaches to the early recognition, diagnosis and therapeutic management of sepsis, giving the clinician the most contemporary and practical approaches with which to treat these patients. PMID:16247103

A Validation Argument for a Simulation-Based Training Course Centered on Assessment, Recognition, and Early Management of Pediatric Sepsis.

PubMed

Geis, Gary L; Wheeler, Derek S; Bunger, Amy; Militello, Laura G; Taylor, Regina G; Bauer, Jerome P; Byczkowski, Terri L; Kerrey, Benjamin T; Patterson, Mary D

2018-02-01

Early recognition of sepsis remains one of the greatest challenges in medicine. Novice clinicians are often responsible for the recognition of sepsis and the initiation of urgent management. The aim of this study was to create a validity argument for the use of a simulation-based training course centered on assessment, recognition, and early management of sepsis in a laboratory-based setting. Five unique simulation scenarios were developed integrating critical sepsis cues identified through qualitative interviewing. Scenarios were piloted with groups of novice, intermediate, and expert pediatric physicians. The primary outcome was physician recognition of sepsis, measured with an adapted situation awareness global assessment tool. Secondary outcomes were physician compliance with pediatric advanced life support (PALS) guidelines and early sepsis management (ESM) recommendations, measured by two internally derived tools. Analysis compared recognition of sepsis by levels of expertise and measured association of sepsis recognition with the secondary outcomes. Eighteen physicians were recruited, six per study group. Each physician completed three sepsis simulations. Sepsis was recognized in 19 (35%) of 54 simulations. The odds that experts recognized sepsis was 2.6 [95% confidence interval (CI) = 0.5-13.8] times greater than novices. Adjusted for severity, for every point increase in the PALS global performance score, the odds that sepsis was recognized increased by 11.3 (95% CI = 3.1-41.4). Similarly, the odds ratio for the PALS checklist score was 1.5 (95% CI = 0.8-2.6). Adjusted for severity and level of expertise, the odds of recognizing sepsis was associated with an increase in the ESM checklist score of 1.8 (95% CI = 0.9-3.6) and an increase in ESM global performance score of 4.1 (95% CI = 1.7-10.0). Although incomplete, evidence from initial testing suggests that the simulations of pediatric sepsis were sufficiently valid to justify their use in training novice

Urine metabolomics in neonates with late-onset sepsis in a case-control study

NASA Astrophysics Data System (ADS)

Sarafidis, Kosmas; Chatziioannou, Anastasia Chrysovalantou; Thomaidou, Agathi; Gika, Helen; Mikros, Emmanouel; Benaki, Dimitra; Diamanti, Elisavet; Agakidis, Charalampos; Raikos, Nikolaos; Drossou, Vasiliki; Theodoridis, Georgios

2017-04-01

Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

Learning representations for the early detection of sepsis with deep neural networks.

PubMed

Kam, Hye Jin; Kim, Ha Young

2017-10-01

Sepsis is one of the leading causes of death in intensive care unit patients. Early detection of sepsis is vital because mortality increases as the sepsis stage worsens. This study aimed to develop detection models for the early stage of sepsis using deep learning methodologies, and to compare the feasibility and performance of the new deep learning methodology with those of the regression method with conventional temporal feature extraction. Study group selection adhered to the InSight model. The results of the deep learning-based models and the InSight model were compared. With deep feedforward networks, the area under the ROC curve (AUC) of the models were 0.887 and 0.915 for the InSight and the new feature sets, respectively. For the model with the combined feature set, the AUC was the same as that of the basic feature set (0.915). For the long short-term memory model, only the basic feature set was applied and the AUC improved to 0.929 compared with the existing 0.887 of the InSight model. The contributions of this paper can be summarized in three ways: (i) improved performance without feature extraction using domain knowledge, (ii) verification of feature extraction capability of deep neural networks through comparison with reference features, and (iii) improved performance with feedforward neural networks using long short-term memory, a neural network architecture that can learn sequential patterns. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reversal of Sepsis-Like Features of Neutrophils by Interleukin-1 Blockade in Patients With Systemic-Onset Juvenile Idiopathic Arthritis.

PubMed

Ter Haar, Nienke M; Tak, Tamar; Mokry, Michal; Scholman, Rianne C; Meerding, Jenny M; de Jager, Wilco; Verwoerd, Anouk; Foell, Dirk; Vogl, Thomas; Roth, Johannes; Leliefeld, Pieter H C; van Loosdregt, Jorg; Koenderman, Leo; Vastert, Sebastiaan J; de Roock, Sytze

2018-06-01

Neutrophils are the most abundant innate immune cells in the blood, but little is known about their role in (acquired) chronic autoinflammatory diseases. This study was undertaken to investigate the role of neutrophils in systemic-onset juvenile idiopathic arthritis (JIA), a prototypical multifactorial autoinflammatory disease that is characterized by arthritis and severe systemic inflammation. Fifty patients with systemic-onset JIA who were receiving treatment with recombinant interleukin-1 receptor antagonist (rIL-1Ra; anakinra) were analyzed at disease onset and during remission. RNA sequencing was performed on fluorescence-activated cell-sorted neutrophils from 3 patients with active systemic-onset JIA and 3 healthy controls. Expression of activation markers, apoptosis, production of reactive oxygen species (ROS), and degranulation of secretory vesicles from neutrophils were assessed by flow cytometry in serum samples from 17 patients with systemic-onset JIA and 15 healthy controls. Neutrophil counts were markedly increased at disease onset, and this correlated with the levels of inflammatory mediators. The neutrophil counts normalized within days after the initiation of rIL-1Ra therapy. RNA-sequencing analysis revealed a substantial up-regulation of inflammatory processes in neutrophils from patients with active systemic-onset JIA, significantly overlapping with the transcriptome of sepsis. Correspondingly, neutrophils from patients with active systemic-onset JIA displayed a primed phenotype that was characterized by increased ROS production, CD62L shedding, and secretory vesicle degranulation, which was reversed by rIL-1Ra treatment in patients who had achieved clinical remission. Patients with a short disease duration had high neutrophil counts, more immature neutrophils, and a complete response to rIL-1Ra, whereas patients with symptoms for >1 month had normal neutrophil counts and an unsatisfactory response to rIL-1Ra. In vitro, rIL-1Ra antagonized the

Lost human capital from early-onset chronic depression.

PubMed

Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

2000-06-01

Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

Disease evolution in late-onset and early-onset systemic lupus erythematosus.

PubMed

Aljohani, R; Gladman, D D; Su, J; Urowitz, M B

2017-10-01

Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis.

PubMed

Pettengill, Matthew; Matute, Juan D; Tresenriter, Megan; Hibbert, Julie; Burgner, David; Richmond, Peter; Millán, José Luis; Ozonoff, Al; Strunk, Tobias; Currie, Andrew; Levy, Ofer

2017-01-01

A host defense function for Alkaline phosphatases (ALPs) is suggested by the contribution of intestinal ALP to detoxifying bacterial lipopolysaccharide (endotoxin) in animal models in vivo and the elevation of ALP activity following treatment of human cells with inflammatory stimuli in vitro. However the activity of ALP in human plasma (primarily tissue-nonspecific ALP; TNAP) on lipopolysaccharide and other microbial products has not been assessed, nor has its expression been studied in preterm newborns, a vulnerable population at high risk of sepsis. In this context, the aim of our study was to characterize the activity of TNAP on Toll-like receptor (TLR) agonists and assess the concentrations of plasma ALP during late-onset sepsis in preterm newborns. Recombinant human TNAP was incubated with microbial products and phosphate release was measured by malachite green assay. Plasma ALP activity was measured serially in a cohort of preterm (N = 129) infants at high risk of late-onset sepsis (LOS). TNAP dephosphorylates poly-inosine:cytosine (Toll-like receptor (TLR) 3 agonist) and LPS from Klebsiella pneumoniae and Salmonella minnesota (TLR4 agonists). Plasma ALP significantly increased postnatally over the first 4 weeks of life in preterm and term newborns. Bacteremic LOS in preterm infants (gestational age ≤ 30 weeks) was associated with significantly elevated plasma ALP at 4 weeks postnatal age. TNAP, the main circulating isozyme of ALP, de-phosphorylates TLR agonists, demonstrates a post-natal age dependent increase in preterm and term plasma across the first 4 weeks of life, and is elevated in association with preterm LOS.

Early post-splenectomy sepsis after missile injury in adults.

PubMed Central

Ellias, Y. A.; Elias, M. A.; Gorey, T. F.

1991-01-01

Early septic complications were studied in 292 patients operated on for penetrating missile injury of the abdomen with involvement of either the spleen or the liver, at Basrah Teaching Hospital between January 1983 and April 1986. Depending on associated injuries, patients with splenectomy were divided into three groups, the first with isolated splenic injury, the second with splenic and associated extra-intestinal organ injury, and the third with splenic and intestinal injuries with or without extra-intestinal organ injury. Patients with hepatic injury were classified similarly. Splenectomy was carried out for any degree of splenic injury. Grade I hepatic injuries were managed by débridement and suturing while major grades II-IV underwent segmentectomy or lobectomy. Patients were considered septic if they had any three of four clinical criteria: temperature higher than 39 degrees C; significant haemodynamic deterioration; respiratory alkalosis, or oliguria. Of the total, 79 were excluded due to: early transfer 51, incomplete records 8, perioperative death 11, and having combined splenic and hepatic injuries 9 (excluded by definition), leaving 104 (74.8%) patients with splenectomy and 109 (71.1%) with hepatic injury available for study. Sepsis developed in 48 (46.1%) of patients after splenectomy and in 28 (25.7%) with hepatic injury. This difference was significant (P greater than 0.005). In patients with isolated splenic injury, eight (25.8%) were septic while three (13.6%) of those with isolated hepatic injury developed sepsis. This was not significant (P = 0.32, Fisher's exact test). When either was associated with an injury to an extra-intestinal organ, 15 (50%) of the splenectomy group developed sepsis compared to five (23.8%) of the hepatic injury group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2042899

Genetics Home Reference: early-onset primary dystonia

MedlinePlus

... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

Routine culture-based screening versus risk-based management for the prevention of early-onset group B streptococcus disease in the neonate: a systematic review.

PubMed

Kurz, Ella; Davis, Deborah

2015-04-17

Early-onset group B streptococcus disease, recognized as the most common cause of early onset neonatal sepsis in developed countries, is transmitted vertically from the group B streptococcus carrier mother to the neonate in the peripartum. Accordingly, early-onset group B streptococcus disease is prevented by halting the transmission of the microorganism from the mother to the infant. Two main methods, routine culture-based screening and risk-based management, may be used in the identification of mothers requiring intrapartum antibiotic prophylaxis in labor. While there are advantages and disadvantages to each, there is limited high level evidence available as to which method is superior. To identify the effectiveness of risk-based management versus routine culture-based screening in the prevention of early-onset group B streptococcus disease in the neonate. This review considered studies which treated pregnant women with intrapartum antibiotic prophylaxis following risk- and culture-based protocols for the prevention of early-onset group B streptococcus disease in the neonate. Types of intervention: This review considered studies that evaluated risk-based management against routine culture-based screening for the prevention of early-onset group B streptococcus disease in the neonate. Types of studies: This review looked for highest evidence available which in this case consisted of one quasi experimental study and eight comparative cohort studies with historical or concurrent control groups. Types of outcomes: Incidence of early-onset group B streptococcus disease in neonates as measured by positive group B streptococcus culture from an otherwise sterile site. Secondary outcomes include neonatal death due to group B streptococcus sepsis and percentage of women who received intrapartum antibiotic prophylaxis. A multi-step search strategy was used to find studies which were limited to the English language and published between January 2000 and June 2013. The quality

Pathogen and antimicrobial resistance profiles of culture-proven neonatal sepsis in Southwest China, 1990-2014.

PubMed

Lu, Qi; Zhou, Min; Tu, Yan; Yao, Yao; Yu, Jialin; Cheng, Shupeng

2016-10-01

Neonatal sepsis (NS) sustains high mortality and morbidity in China, but data on the epidemiology and antimicrobial resistance patterns of NS pathogens are limited. The clinical features, aetiology and antimicrobial resistance of culture-proven NS were analysed over a period of 25 years in the metropolitan city of Chongqing in Southwest China. The occurrence rates of neonatal early-onset sepsis (EOS) were found to gradually decrease while late-onset sepsis (LOS) was kept stable from 1990 to 2014. Although coagulase-negative staphylococcus (CoNS) sepsis accounted for most infections, the occurrence rates of CoNS sepsis gradually decreased, especially in EOS. Escherichia coli and Klebsiella were common Gram-negative bacteria. The occurrence rates of E. coli and Klebsiella remained stable in EOS; however, in LOS, those had increased mildly, especially from 2009 to 2014. Although a high-degree resistance to common first- and second-line antimicrobials was observed for the main causative pathogens of NS, the gentamicin-resistance rate declined gradually from the year 2003. Similarly, the ceftazidime-resistance rate of E. coli dropped gradually from the year 2007. The alarmingly high degree of antibiotic resistance calls for urgent evaluation and development of antibiotic policy and protocols for the treatment of NS. Clinicians should strictly control the antibiotics use, decrease invasive manipulations and shorten hospitalisation to prevent LOS. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Mechanisms of intestinal barrier dysfunction in sepsis

PubMed Central

Yoseph, Benyam P.; Klingensmith, Nathan J.; Liang, Zhe; Breed, Elise R.; Burd, Eileen M.; Mittal, Rohit; Dominguez, Jessica A.; Petrie, Benjamin; Ford, Mandy L.; Coopersmith, Craig M.

2016-01-01

Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 hours later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at six to 12 hours. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13 and 15, JAM-A, occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 hours after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 hour after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis induce a significant increase

Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

PubMed

Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

2016-07-01

Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder

PubMed Central

Croarkin, Paul E.; Luby, Joan L.; Cercy, Kelly; Geske, Jennifer R.; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T.; Wagner, Karen Dineen; Walkup, John T.; Nassan, Malik M.; Cuellar-Barboza, Alfredo B.; Casuto, Leah; McElroy, Susan L.; Jensen, Peter S.; Frye, Mark A.; Biernacka, Joanna M.

2018-01-01

Objective In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder. Method Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003–2008. Mayo Clinic Bipolar Biobank samples were collected from 2009–2013. Genotyping and analyses for the present study took place from 2013–2014. The diagnosis of bipolar disorder was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with bipolar disorder, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly “odz, odd Oz/ten-m homolog 4 {Drosophila}, ODZ4”]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n=69), adult patients with bipolar disorder (n=732) including a subset with early-onset illness [n=192]), and healthy controls (n=776). GRS analyses were performed comparing early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. Results GRS analysis revealed associations of the risk score with early-onset bipolar disorder (P=.01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset bipolar disorder with a CACNA1C haplotype (global test, P=.01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset bipolar disorder (P=.017), which did not remain significant after correction for multiple comparisons. Conclusion These preliminary analyses suggest that previously identified bipolar disorder risk loci

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

PubMed

Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD. �

Changing Definitions of Sepsis

PubMed Central

Gül, Fethi; Arslantaş, Mustafa Kemal; Cinel, İsmail; Kumar, Anand

2017-01-01

Sepsis is one of the main causes of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies. Outcomes in sepsis have improved overall, probably because of an enhanced focus on early diagnosis and other improvements in supportive care, but mortality rates still remain unacceptably high. The diagnosis and definition of sepsis is a critical problem due to the heterogeneity of this disease process. Although it is apparent that much more needs to be done to advance our understanding, sepsis and related terms remain difficult to define. A 1991 consensus conference developed initial definitions that systemic inflammatory response syndrome (SIRS) to infection would be called sepsis. Definitions of sepsis and septic shock were revised in 2001 to incorporate the threshold values for organ damage. In early 2016, the new definitions of sepsis and septic shock have changed dramatically. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The consensus document describes organ dysfunction as an acute increase in total Sequential Organ Failure Assessment (SOFA) score two points consequently to the infection. A significant change in the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task Force also introduced a new bedside index, called the qSOFA, to identify outside of critical care units patients with suspected infection who are likely to develop sepsis. Recently updated the consensus definitions improved specificity compared with the previous descriptions. PMID:28752002

Evidence for a genetic etiology of early-onset delinquency.

PubMed

Taylor, J; Iacono, W G; McGue, M

2000-11-01

Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

NASA Astrophysics Data System (ADS)

Sinto, R.; Widodo, D.; Pohan, H. T.

2018-03-01

Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome.

PubMed

Romeo, M G; Romeo, D M; Trovato, L; Oliveri, S; Palermo, F; Cota, F; Betta, P

2011-01-01

To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by Candida species, of late-onset sepsis and neurological outcome in preterm newborns. A prospective study was conducted in 249 preterms who were subdivided into three groups: one group (n=83) was supplemented with Lactobacillus (L.) reuteri, one group with L. rhamnosus (n=83) and the other with no supplementation (n=83). The fungal colonization in the gastrointestinal tract, the late onset of sepsis and clinical parameters were recorded. A neurological structured assessment was further performed at 1 year of age. Candida stool colonization was significantly higher (P<0.01) in the control group than in the groups treated with probiotics. The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups. Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group. The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by Candida, in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms.

Identifying hospital-onset Escherichia coli bacteraemia cases from English mandatory surveillance: the case for applying a two-day post-admission rule.

PubMed

Davies, J; Johnson, A P; Hope, R

2017-11-01

A national voluntary surveillance programme has shown year-on-year increases in the number of bacteraemias caused by Escherichia coli. Mandatory surveillance of E. coli bacteraemia was introduced in 2011 with the aim of improving the quantity and quality of data collected. In contrast to the other national mandatory surveillance programmes, cases are not currently categorized based upon time of onset in relation to hospital admission. To assess the case for applying time-of-onset categorization to cases of E. coli bacteraemia in England. Data for all cases of E. coli bacteraemia reported to Public Health England between April 2012 and March 2016 were extracted from the national mandatory surveillance database. Cases were categorized as hospital-onset if positive blood cultures were obtained two or more days after admission. Approximately 21% of cases were categorized as hospital-onset. However, the proportion of hospital-onset cases decreased by 1% in each successive 12-month period, from 23% in 2012/13 to 20% in 2015/16 (P<0.001). Approximately one-fifth of E. coli bacteraemia cases reported via mandatory surveillance were identified as hospital-onset. Given that prevention and control strategies will vary by setting, the routine feedback of this information will prove important in informing infection prevention and control efforts. The categorization of this subset of cases represents an important step towards better understanding of the epidemiology of E. coli bacteraemia. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Incidence, disease onset and short-term outcome in urea cycle disorders -cross-border surveillance in Germany, Austria and Switzerland.

PubMed

Nettesheim, Susanne; Kölker, Stefan; Karall, Daniela; Häberle, Johannes; Posset, Roland; Hoffmann, Georg F; Heinrich, Beate; Gleich, Florian; Garbade, Sven F

2017-06-15

Urea cycle disorders (UCDs) are a group of rare inherited metabolic disorders. Affected individuals often present with hyperammonemic encephalopathy (HE) and have an increased risk of severe neurologic disease and early death. The study aims to provide epidemiologic data and to describe the disease manifestation and short-term outcome. Cross-border surveillance of newly diagnosed patients with UCDs - below 16 years of age - was performed from July 2012 to June 2015 in Germany and Austria and from January 2012 to December 2015 in Switzerland. Inquiries were sent monthly to all Pediatric Departments in Germany and Switzerland, and quarterly to the Austrian Metabolic Group. In addition, data were collected via a second source (metabolic laboratories) in all three countries. Between July 2012 and June 2015, fifty patients (Germany: 39, Austria: 7, Switzerland: 4) with newly diagnosed UCDs were reported and later confirmed resulting in an estimated cumulative incidence of 1 in 51,946 live births. At diagnosis, thirty-nine patients were symptomatic and 11 asymptomatic [10 identified by newborn screening (NBS), 1 by high-risk-family screening (HRF)]. The majority of symptomatic patients (30 of 39 patients) developed HE with (n = 25) or without coma (n = 5), 28 of them with neonatal onset. Despite emergency treatment 15 of 30 patients with HE already died during the newborn period. Noteworthy, 10 of 11 patients diagnosed by NBS or HRF remained asymptomatic. Comparison with the European registry and network for intoxication type metabolic diseases (E-IMD) demonstrated that cross-national surveillance identified a higher number of clinically severe UCD patients characterized by earlier onset of symptoms, higher peak ammonium concentrations in plasma and higher mortality. Cross-border surveillance is a powerful tool to identify patients with UCDs demonstrating that (1) the cumulative incidence of UCDs is lower than originally suggested, (2) the mortality rate is still

Epidemiology of UK neonatal infections: the neonIN infection surveillance network.

PubMed

Cailes, Benjamin; Kortsalioudaki, Christina; Buttery, Jim; Pattnayak, Santosh; Greenough, Anne; Matthes, Jean; Bedford Russell, Alison; Kennea, Nigel; Heath, Paul T

2017-12-05

To describe the epidemiology of neonatal infection over the past decade in UK neonatal units. Retrospective analysis of prospectively collected infection surveillance network data from 2005 to 2014. 30 neonatal units in the UK. Newborns on participating neonatal units who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of appropriate antibiotics. 2171 episodes of neonatal infection in 1922 infants were recorded. The incidence of infection was 6.1/1000 live births and 48.8/1000 neonatal admissions (2.9 and 23.5 respectively if coagulase-negative staphylococci (CoNS) cultures excluded). The incidence of infection showed a statistically significant reduction over time with reductions in the rates of both early-onset sepsis (EOS) and late-onset sepsis (LOS).The majority of episodes (76%) represented LOS (diagnosed > 48 hours after birth), and infection was more common in premature (<37 weeks gestation) and low birth weight (<2500 g) neonates (84% and 81%, respectively). Commonly identified pathogens included group B streptococci (43%) and Escherichia coli (18%) for EOS, while E. coli (15%), Staphylococcus aureus (14%) and CoNS were prominent causes of LOS. This paper describes the epidemiology of neonatal infection in the UK over the past decade. These data enable benchmarking of practice and inform areas of future research and guideline development. The results support the hypothesis that the introduction of infection prevention care bundles and antibiotic stewardship programmes in the UK has reduced the burden of LOS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

PubMed

Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

2008-03-15

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

Adrenomedullin and adrenomedullin binding protein-1 attenuate vascular endothelial cell apoptosis in sepsis.

PubMed

Zhou, Mian; Simms, H Hank; Wang, Ping

2004-08-01

To determine whether vascular endothelial cell apoptosis occurs in the late stage of sepsis and, if so, whether administration of a potent vasodilatory peptide adrenomedullin and its newly reported specific binding protein (AM/AMBP-1) prevents sepsis-induced endothelial cell apoptosis. Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Our recent studies have shown that administration of AM/AMBP-1 delays or even prevents the transition from the hyperdynamic phase to the hypodynamic phase of sepsis, attenuates tissue injury, and decreases sepsis-induced mortality. However, the mechanisms responsible for the beneficial effects of AM/AMBP-1 in sepsis remain unknown. Polymicrobial sepsis was induced by cecal ligation and puncture in adult male rats. Human AMBP-1 (40 microg/kg body weight) was infused intravenously at the beginning of sepsis for 20 minutes and synthetic AM (12 microg/kg body weight) was continuously administered for the entire study period using an Alzert micro-osmotic pump, beginning 3 hours prior to the induction of sepsis. The thoracic aorta and pulmonary tissues were harvested at 20 hours after cecal ligation and puncture (ie, the late stage of sepsis). Apoptosis was determined using TUNEL assay, M30 Cytodeath immunostaining, and electromicroscopy. In addition, anti-apoptotic Bcl-2 and pro-apoptotic Bax gene expression and protein levels were assessed by RT-PCR and Western blot analysis, respectively. Vascular endothelial cells underwent apoptosis formation at 20 hours after cecal ligation and puncture as determined by three different methods. Moreover, partial detached endothelial cell in the aorta was observed. Bcl-2 mRNA and protein levels decreased significantly at 20 hours after the onset of sepsis while Bax was not altered. Administration of AM/AMBP-1 early after sepsis, however, significantly reduced the number of apoptotic endothelial cells. This was associated with significantly

Procalcitonin for the early diagnosis of sepsis in burn patients: A retrospective study.

PubMed

Cabral, Luís; Afreixo, Vera; Santos, Filipe; Almeida, Luís; Paiva, José Artur

2017-11-01

The gold standard for sepsis diagnosis in burn patient still relies on microbiological cultures, which take 48-72h to provide results, delaying the start of antimicrobial therapy. Thus, biomarkers allowing an earlier sepsis diagnosis in burn patients are needed. This retrospective observational study included 150 burn patients with total burned surface area ≥15%. Clinical diagnosis of sepsis among these patients was done according to the American Burn Association criteria. Biomarker (procalcitonin, white blood cells and platelet countings, prothrombinemia, D-dimers, C-reactive protein, blood lactate and temperature) values were available for 48 patients without sepsis (2767 timepoints) and 102 patients with sepsis (652 timepoints). Quantitative variables were compared with Mann-Whitney tests and qualitative variables were compared with Pearson chi-square test. Effect size was measured by the probability of superiority. Receiver operating characteristic (ROC) curves evaluate capacity for sepsis diagnosis. Sensitivity, specificity, positive and negative predictive values were calculated for some cut-off values, including the best cut-off defined by the maximum of Youden index. Statistically significant differences between the groups of septic and non-septic patients, with medium to large effect size, were detected for all the biomarkers considered, except temperature. PCT was the biomarker with the largest AUC and effect size (AUC=0.71). Analysis of the PCT ROC curve showed that 0.5ng/mL cut-off presented highest sensitivity and lowest specificity, whereas 1.5ng/mL cut-off was associated with lowest sensitivity and highest specificity. Procalcitonin showed to be the best of the biomarkers studied for an early diagnosis of sepsis. Its use should be considered in antimicrobial stewardship programs in Burn Units. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

PubMed

Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

2017-10-26

To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

Obstetrical outcomes in patients with early onset gestational diabetes.

PubMed

Gupta, Simi; Dolin, Cara; Jadhav, Ashwin; Chervenak, Judith; Timor-Tritsch, Ilan; Monteagudo, Ana

2016-01-01

The objective of this study was to characterize patients with early onset gestational diabetes and compare outcomes to patients diagnosed with standard gestational diabetes and pregestational diabetes. This is a retrospective cohort study of patients diagnosed with gestational or pregestational diabetes. All patients received a glucose challenge test at their first prenatal visit to diagnose early onset gestational diabetes and were recommended to have postpartum glucose tolerance tests to detect undiagnosed type 2 diabetes. Outcomes were compared between patients with early onset gestational diabetes and both standard gestational diabetes and pregestational diabetes with p < 0.05 was used for significance. Four hundred and twenty-four patients met the inclusion criteria. Nine percent of the patients with early onset gestational diabetes were found to have undiagnosed type 2 diabetes based on postpartum testing and 91% to have resolution in the postpartum period. No patient with early onset gestational diabetes and resolution in the postpartum period had abnormal screening for renal or ophthalmologic disease, but 5% had abnormal fetal echocardiograms. These patients were more likely to require pharmacotherapy for glycemic control than patients with standard gestational diabetes and less likely than patients with pregestational diabetes (55% versus 39% versus 81%). Most patients diagnosed with early onset gestational diabetes do not have undiagnosed type 2 diabetes but do have unique characteristics and obstetrical outcomes.

Diagnosis and management of sepsis

NASA Astrophysics Data System (ADS)

Arifin

2018-03-01

Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.

Sepsis 2018: Definitions and Guideline Changes.

PubMed

Napolitano, Lena M

Sepsis is a global healthcare issue and continues to be the leading cause of death from infection. Early recognition and diagnosis of sepsis is required to prevent the transition into septic shock, which is associated with a mortality rate of 40% or more. New definitions for sepsis and septic shock (Third International Consensus Definitions for Sepsis and Septic Shock [Sepsis-3]) have been developed. A new screening tool for sepsis (quick Sequential Organ Failure Assessment [qSOFA]) has been proposed to predict the likelihood of poor outcome in out-of-intensive care unit (ICU) patients with clinical suspicion of sepsis. The Surviving Sepsis Campaign Guidelines were recently updated and include greater evidence-based recommendations for treatment of sepsis in attempts to reduce sepsis-associated mortality. This review discusses the new Sepsis-3 definitions and guidelines.

Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

PubMed

Black, Donald W; Shaw, Martha; Coryell, William; Crowe, Raymond; McCormick, Brett; Allen, Jeff

2015-07-01

Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Unusual early-onset Huntingtons disease.

PubMed

Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

2003-06-01

Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

Performance of the definitions of the systemic inflammatory response syndrome and sepsis in neonates.

PubMed

Hofer, Nora; Zacharias, Eva; Müller, Wilhelm; Resch, Bernhard

2012-09-01

The aim of this study was to examine the applicability of the definitions of the systemic inflammatory response syndrome (SIRS) and sepsis to neonates during the first 3 days of life. This is a retrospective study of all term neonates hospitalized within the first 24 h of life from 2004 to 2010 at our neonatal intensive care unit. Of 476 neonates, 30 (6 %) had a diagnosis of culture-proven early-onset sepsis (EOS) and 81 (17 %) had culture-negative clinical EOS or suspected EOS. SIRS and sepsis criteria were applied to 116 (24 %) and 61 (13 %) neonates, respectively. Of 30 neonates with culture proven, EOS 14 (53 %) fulfilled SIRS and sepsis criteria. The single diagnostic criterion of SIRS applied to 20 % (hypothermia or fever), 43 % (white blood cell count/immature-to-total neutrophil ratio), 87 % (respiratory symptoms), and 33 % (cardiocirculatory symptoms) of all neonates with culture-proven EOS. The definitions of SIRS and sepsis did not apply to about half of all cases of culture-proven EOS. An evidence-based approach to find the appropriate criteria for defining EOS in the neonate is needed.

Sepsis in Pediatric Cardiac Intensive Care.

PubMed

Wheeler, Derek S; Wong, Hector R

2016-08-01

In this review, we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, in monitoring therapeutic efficacy, in stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function. MEDLINE and PubMed. There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis.

Reductions in Sepsis Mortality and Costs After Design and Implementation of a Nurse-Based Early Recognition and Response Program

PubMed Central

Jones, Stephen L.; Ashton, Carol M.; Kiehne, Lisa; Gigliotti, Elizabeth; Bell-Gordon, Charyl; Disbot, Maureen; Masud, Faisal; Shirkey, Beverly A.; Wray, Nelda P.

2016-01-01

Background Sepsis is a leading cause of death, but evidence suggests that early recognition and prompt intervention can save lives. In 2005 Houston Methodist Hospital prioritized sepsis detection and management in its ICU. In late 2007, because of marginal effects on sepsis death rates, the focus shifted to designing a program that would be readily used by nurses and ensure early recognition of patients showing signs suspicious for sepsis, as well as the institution of prompt, evidence-based interventions to diagnose and treat it. Methods The intervention had four components: organizational commitment and data-based leadership; development and integration of an early sepsis screening tool into the electronic health record; creation of screening and response protocols; and education and training of nurses. Twice-daily screening of patients on targeted units was conducted by bedside nurses; nurse practitioners initiated definitive treatment as indicated. Evaluation focused on extent of implementation, trends in inpatient mortality, and, for Medicare beneficiaries, a before-after (2008–2011) comparison of outcomes and costs. A federal grant in 2012 enabled expansion of the program. Results By year 3 (2011) 33% of inpatients were screened (56,190 screens in 9,718 unique patients), up from 10% in year 1 (2009). Inpatient sepsis-associated death rates decreased from 29.7% in the preimplementation period (2006–2008) to 21.1% after implementation (2009–2014). Death rates and hospital costs for Medicare beneficiaries decreased from preimplementation levels without a compensatory increase in discharges to postacute care. Conclusion This program has been associated with lower inpatient death rates and costs. Further testing of the robustness and exportability of the program is under way. PMID:26484679

Improved Early Detection of Sepsis in the ED With a Novel Monocyte Distribution Width Biomarker.

PubMed

Crouser, Elliott D; Parrillo, Joseph E; Seymour, Christopher; Angus, Derek C; Bicking, Keri; Tejidor, Liliana; Magari, Robert; Careaga, Diana; Williams, JoAnna; Closser, Douglas R; Samoszuk, Michael; Herren, Luke; Robart, Emily; Chaves, Fernando

2017-09-01

Sepsis most often presents to the ED, and delayed detection is harmful. WBC count is often used to detect sepsis, but changes in WBC count size also correspond to sepsis. We sought to determine if volume increases of circulating immune cells add value to the WBC count for early sepsis detection in the ED. A blinded, prospective cohort study was conducted in two different ED populations within a large academic hospital. Neutrophil and monocyte volume parameters were measured in conjunction with routine CBC testing on a UniCel DxH 800 analyzer at the time of ED admission and were evaluated for the detection of sepsis. There were 1,320 subjects in the ED consecutively enrolled and categorized as control subjects (n = 879) and those with systemic inflammatory response syndrome (SIRS) (n = 203), infection (n = 140), or sepsis (n = 98). Compared with other parameters, monocyte distribution width (MDW) best discriminated sepsis from all other conditions (area under the curve [AUC], 0.79; 95% CI, 0.73-0.84; sensitivity, 0.77; specificity, 0.73; MDW threshold, 20.50), sepsis from SIRS (AUC, 0.74; 95% CI, 0.67-0.84), and severe sepsis from noninfected patients in the ED (AUC, 0.88; 95% CI, 0.75-0.99; negative predictive value, 99%). The added value of MDW to WBC count was statistically significant (AUC, 0.89 for MDW + WBC vs 0.81 for WBC alone; P < .01); a decision curve analysis also showed improved performance compared with WBC count alone. The incorporation of MDW with WBC count is shown in this prospective cohort study to improve detection of sepsis compared with WBC count alone at the time of admission in the ED. ClinicalTrials.gov; No.: NCT02232750; URL: www.clinicaltrials.gov. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Analysis of sepsis in allogeneic bone marrow transplant recipients: a single-center study.

PubMed

Mitsui, Hideki; Karasuno, Takahiro; Santo, Taisuke; Fukushima, Kentaro; Matsunaga, Hitomi; Nakamura, Hiroyuki; Hiraoka, Akira

2003-09-01

We reviewed the records of 235 consecutive recipients of allogeneic bone marrow transplantation (allo-BMT) at our center between February 1983 and October 2000. Sepsis occurred in 25 patients (10.6%) at a median of 10 days (range, 1-280 days) after BMT. Five of the 25 patients (20%) died of sepsis. Pathogens isolated from blood culture were gram-positive cocci in 19 patients, gram-negative rods in 7, fungi in 2, and others in 1 patient. Two pathogens were detected concomitantly in 4 patients. Univariate analysis revealed that risk factors for sepsis were selective gut decontamination using lomefloxacin hydrochloride and nystatin, an unrelated donor, HLA mismatched BMT, and stomatitis. Multivariate logistic regression analysis revealed that an unrelated donor was the only significant independent risk factor, with a relative risk of 5.432. In 12 of 25 patients with sepsis, the pathogens of sepsis were sensitive to antibiotics used for gut decontamination. Selective gut decontamination significantly increased the incidence of sepsis, especially that with gram-positive cocci, but not the mortality rate of sepsis, compared with total gut decontamination using vancomycin. We also found a significant relationship between pathogens isolated from blood culture and those isolated from surveillance cultures of stool, urine, and gargled water in the period before sepsis occurred. The present study revealed an independent risk factor for sepsis (unrelated donor), the feasibility of selective gut decontamination, and the importance of surveillance culture.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

PubMed

von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

2011-04-01

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulation.

PubMed

Eguchi, Yutaka; Gando, Satoshi; Ishikura, Hiroyasu; Saitoh, Daizoh; Mimuro, Jun; Takahashi, Hoyu; Kitajima, Isao; Tsuji, Hajime; Matsushita, Tadashi; Tsujita, Ryuichi; Nagao, Osamu; Sakata, Yoichi

2014-01-01

Thrombomodulin alfa (TM-α, recombinant thrombomodulin) significantly improved disseminated intravascular coagulation (DIC) when compared with heparin therapy in a phase III study. Post-marketing surveillance of TM-α was performed to evaluate the effects and safety in patients with sepsis-induced DIC. From May 2008 to April 2010, a total of 1,787 patients with sepsis-induced DIC treated with TM-α were registered. DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) criteria. The DIC resolution and survival rates on day 28 after the last TM-α administration, and changes in DIC, systemic inflammatory response syndrome (SIRS), and sequential organ failure assessment (SOFA) scores and coagulation and inflammation markers were evaluated. The most frequent underlying disease was infectious focus-unknown sepsis (29.8%). The mean ± SD values of age, dose, and the duration of TM-α administration were 64.7 ± 20.3 years, 297.3 ± 111.4 U/kg/day, and 5.6 ± 3.4 days, respectively. A total of 1,320 subjects (73.9%) received combined administration with other anticoagulants. Both coagulation and inflammation markers, such as fibrin/fibrinogen degradation products, prothrombin time ratio, thrombin-antithrombin complex, and C-reactive protein, as well as JAAM DIC, SIRS, and SOFA scores, significantly and simultaneously decreased after TM-α administration (p < 0.001). DIC resolution and 28-day survival rates were 44.4% and 66.0%, respectively. The 28-day survival rate decreased significantly according to the duration of DIC before TM-α administration (p < 0.001). Total adverse drug reactions (ADRs), bleeding ADRs, and serious bleeding adverse events occurred in 126 (7.1%), 98 (5.5%), and 121 (6.8%) subjects, respectively. On day 28, after the last TM-α administration available for an antibody test, only one patient was positive for anti-TM-α antibodies (0.11%). Our results suggest that TM-α is most effective for treating

A blueprint for a sepsis protocol.

PubMed

Shapiro, Nathan I; Howell, Michael; Talmor, Daniel

2005-04-01

Despite numerous advances in medicine, sepsis remains an unconquered challenge. Although outcomes have improved slightly over decades, the unacceptably high mortality rate of 30%-50% for severe sepsis and septic shock continues. However, after years of unsuccessful clinical trials, several investigations over the last few years have reported survival benefit in the treatment of sepsis. Physicians now have several proven therapies to treat sepsis, but have yet to implement them on a widespread, systematic basis. This led 11 international professional societies spanning multiple specialties and continents to come together to create the Surviving Sepsis Campaign. The product of their work is an international effort organized to improve care of patients with sepsis and includes consensus, evidence-based guidelines for care that improves survival in septic patients, and an action plan for change. Given the clear role of early identification and treatment in stopping the sepsis cascade, therapy must start early in the emergency department (ED) and continue throughout the hospital course. The first of the recommendations by the Surviving Sepsis Campaign is the aggressive resuscitation strategy of early goal-directed therapy (EGDT). EGDT is reported to reduce absolute mortality by a staggering 16%. The use of recombinant activated protein C was demonstrated to confer a 6% absolute survival benefit. Steroid supplementation in adrenal insufficiency produced a 10% benefit. Additionally, early and appropriate use of antibiotics remains a cornerstone of therapy. Although no randomized trial will be performed, the effects are undisputed. Finally, although predominantly intensive care unit therapies, tight glucose control and low-tidal-volume ventilation strategies have also led to improved survival. Armed with these new therapies, the medical community must rise to this call to action. Clinicians must change the approach to this disease, as well as the way the septic patient is

Gut microbial colonisation in premature neonates predicts neonatal sepsis

PubMed Central

Madan, Juliette C; Salari, Richard Cowper; Saxena, Deepti; Davidson, Lisa; O’Toole, George A; Moore, Jason H; Sogin, Mitchell L; Foster, James A; Edwards, William H; Palumbo, Paul; Hibberd, Patricia L

2013-01-01

Background Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality. Understanding microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome. Methods Prospective longitudinal study of premature infants. Stool samples were obtained weekly. DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing, comparing subjects with and without sepsis. Results Six neonates were 24–27 weeks gestation at birth and had 18 samples analysed. Two subjects had no sepsis during the study period, two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation. 324 350 sequences were obtained. The meconium was not sterile and had predominance of Lactobacillus, Staphylococcus and Enterobacteriales. Overall, infants who developed sepsis began life with low microbial diversity, and acquired a predominance of Staphylococcus, while healthy infants had more diversity and predominance of Clostridium, Klebsiella and Veillonella. Conclusions In very low birth weight infants, the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis. Empiric, prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis, but the predominant pathogen previously identified in the microbiome. Our data suggest that there may be a ‘healthy microbiome’ present in extremely premature neonates that may ameliorate risk of sepsis. More research is needed to determine whether altered antibiotics, probiotics or other novel therapies can re-establish a healthy microbiome in neonates. PMID:22562869

Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

PubMed

Smeets-Janssen, M M J; Meesters, P D; Comijs, H C; Eikelenboom, P; Smit, J H; de Haan, L; Beekman, A T F; Stek, M L

2013-11-01

Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2)  = 0.2). These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted. Copyright © 2013 John Wiley & Sons, Ltd.

Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia.

PubMed

Kocherlakota, P; La Gamma, E F

1997-07-01

To determine whether adjunctive therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival compared with conventional therapy in a phase I/II-type trial. An intravenous infusion of rhG-CSF (10 microg/kg/d x 3 d) was administered to 14 septic neutropenic neonates. Neutrophilic responses and outcome of these neonates were compared with 11 concurrently treated, retrospectively selected, case-matched control septic patients identified by using a search of medical records coded for sepsis with neutropenia (>/=24 hours). Seven neonates with early-onset sepsis with neutropenia at birth and seven neonates with late-onset sepsis plus neutropenia (all with necrotizing enterocolitis) were entered in the rhG-CSF treatment group. Results were compared with a conventional therapy control group (five early onset, six late onset). No significant differences existed in the birth weight, gestational age, use of antibiotic therapy, magnitude of respiratory support, severity of metabolic acidosis, use of vasopressors, or other supportive therapy between the two groups. In the rhG-CSF-treated group and in the conventionally treated control group, the absolute neutrophil count (ANC) (mean +/- SEM) was 585 +/- 138 and 438 +/- 152, respectively. The ANC increased to more than baseline in the rhG-CSF-treated group by 10-fold versus 2-fold at 24 hours, 18-fold versus 4-fold at 48 hours, 24-fold versus 5-fold at 72 hours (significant by one-way analysis of variance in the rhG-CSF group only), and 29-fold versus 16-fold at 7 to 10 days when compared with the conventional therapy group. There were no nonresponders in the rhG-CSF group by 24 hours after the first dose of study drug. Monocyte cell counts also increased significantly in both groups by 7 days after entry into this protocol but remained within normal range for age. No clinically significant effect on lymphocytes, erythrocytes, or

Sepsis in Pediatric Cardiac Intensive Care

PubMed Central

Wheeler, Derek S.; Wong, Hector R.

2016-01-01

Objectives In this review we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, monitoring therapeutic efficacy, stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function. Data Source MEDLINE, PubMed Conclusion There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis. PMID:27490609

Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification.

PubMed

Giamarellos-Bourboulis, E J; Tsaganos, T; Tsangaris, I; Lada, M; Routsi, C; Sinapidis, D; Koupetori, M; Bristianou, M; Adamis, G; Mandragos, K; Dalekos, G N; Kritselis, I; Giannikopoulos, G; Koutelidakis, I; Pavlaki, M; Antoniadou, E; Vlachogiannis, G; Koulouras, V; Prekates, A; Dimopoulos, G; Koutsoukou, A; Pnevmatikos, I; Ioakeimidou, A; Kotanidou, A; Orfanos, S E; Armaganidis, A; Gogos, C

2017-02-01

Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting. Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality. In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004). Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Comparing Characteristics of Early-Onset Injection Drug Users to Those With Late-Onset Injection in Kermanshah, Iran.

PubMed

Jorjoran Shushtari, Zahra; Noroozi, Alireza; Mirzazadeh, Ali; Ahounbar, Elahe; Hajbi, Ahmad; Najafi, Mohammad; Bazrafshan, Ali; Farhadi, Mohammad Hossin; Farhoudian, Ali; Higgs, Peter; Shahboulagh, Farahnaz Mohammadi; Waye, Katherine; Noroozi, Mehdi

2017-05-12

Characteristics and behaviors of early-onset injection drug users are under studied topics in Iran. This study aimed to identify and compare the demographic characteristics as well as the drug using behaviors of early-onset and late-onset injection drug users in Kermanshah, West Iran. In this cross-sectional study using snowball and convenience sampling, we recruited 450 people during the Fall of 2014 from two drop in centers in Kermanshah, Iran. We collected data through face-to-face interviews. Early-onset injection is defined as whether the person reported their first injection at 22 years of age or younger. Subsequently, late-onset injection is defined as 23 years of age or older. We compared the characteristics of the two groups through both univariate and multiple logistic analyses. Overall, 54% (CI 95%: 44.3%, 62.2%) were early injectors. After controlling for low socioeconomic status, initiation of drug use at a young age, multiple drug use and methamphetamine use were all significantly associated with a higher likelihood of early-onset injection. Additionally, early-onset injection was associated with recent syringe borrowing (OR = 2.6, p = 0.001), recent syringe lending (OR = 1.4, p = 0.01), recent cooker sharing (OR = 3.2, p = 0.01) and injecting two or more times a day (OR = 2.2, p = 0.04). Early-onset injectors were more likely to report a lower socioeconomic status, initiation of first drug use at a younger age, using methamphetamine alongside polydrug use, and engaging in higher risk taking behaviors like borrowing needles. With these associations, the study emphasizes the need for drug-prevention programs to focus on the transition to injection drug use at younger ages.

Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

PubMed

Devanand, D P; Adorno, Elizabeth; Cheng, Jocelyn; Burt, Tal; Pelton, G H Gregory H; Roose, S P Steven P; Sackeim, H A Harold A

2004-03-01

Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. Academic clinic sample results may not generalize to community populations. In the

Sepsis and Septic Shock Strategies.

PubMed

Armstrong, Bracken A; Betzold, Richard D; May, Addison K

2017-12-01

Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Pediatric sepsis

PubMed Central

Randolph, Adrienne G; McCulloh, Russell J

2014-01-01

Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the child’s age and immune capacity, and to the site, severity, and source of the infection. It is important for clinicians to be aware of infection-related syndromes that primarily affect children. Although children in developed countries are more likely to survive severe infections than adults, many survivors have chronic health impairments. PMID:24225404

Early bronchiectasis in cystic fibrosis detected by surveillance CT.

PubMed

Pillarisetti, Naveen; Linnane, Barry; Ranganathan, Sarath

2010-08-01

There is emerging evidence that cystic fibrosis lung disease begins early in infancy. Newborn screening allows early detection and surveillance of pulmonary disease and the possibility of early intervention in this life-shortening condition. We report two children with cystic fibrosis who underwent a comprehensive assessment from diagnosis that included measurement of lung function, limited-slice high-resolution CT and BAL performed annually. Early aggressive surveillance enabled significant lung disease and bronchiectasis to be detected during the first few years of life and led to a change in management, highlighting a clinical role for CT scanning during the preschool years in children with cystic fibrosis.

[Severe late-onset group B streptococcal infection. A case report].

PubMed

Haase, Roland; Nagel, Frank; Hirsch, Wolfgang; Sitka, Uwe

2003-01-01

Group B Streptococcus (GBS) is a well-known cause of neonatal pneumonia, sepsis and meningitis. Peripartal antibiotic prophylaxis for early-onset GBS infection is in routine use since the beginning of the last decade, but strategies for effective prevention of late-onset GBS infections are still lacking. Few hours after discharge from a non-local maternity ward a 3-week-old boy was admitted to our hospital because of GBS meningitis with necrotizing encephalomalacia. Maternal mastitis, not a disease of the baby, had led to the first admission. Case history and negative maternal swabs and cultures for GBS led to the hypothesis of nosocomial infection. Screening and risk based peripartal antibiotic prophylaxis, better monitoring and improved therapeutic modalities have reduced the incidence and mortality of early-onset GBS infections, but peripartal prophylaxis failed to influence late-onset GBS infections. Up to 40 % of infants with late-onset meningitis develop neurological sequelae. Maternal vaccination with multivalent conjugate vaccines against GBS is a new strategy which may lead to passive protection of the infant. Further studies to examine the efficacy of vaccines are in progress.

Comparison of the therapeutic effects of tri-iodothyronine and methylprednisolone during early sepsis in laboratory animals.

PubMed

Coskun, F; Saylam, B; Kulah, B; Dolapci, I; Sungur, A; Ozer, M Vasfi

2012-01-01

Despite major advances, the treatment of sepsis is still a challenging problem for surgeons. This study was aimed to compare the therapeutic effects of methylprednisolone and tri-iodothyronine replacement therapy during an early sepsis. Forty male Wistar albino rats weighing 300-340 g were divided into the Control, CLP, CLP/MP, CLP/T3 and CLP/MP/T3 groups. The Control group underwent a sham operation. Only cecal ligation and puncture was performed in the CLP group. The CLP/MP groups received an intramuscular injection of (MP) methylprednisolone (30 mg/kg) at one and half hour before CLP. The CLP/T3 group was given an intraperitoneal (IP) injection of tyroid hormone (T3) 0.4 µg/100 g immediately after CLP. The CLP/MP/T3 group was given IM injection of MP 30 mg/kg before CLP and IP injection of T3 0.4 µg/100 g after CLP. Hemavet changes, blood cultures, peritoneal bacteria content, hormonal alterations and histopathologic changes of intestinal, lung and liver tissue were used to asses the possible therapeutic effects of MP and T3 during early sepsis. A septic insult resulted in significant alterations on hemavet values, free T3, free T4 and cortisol levels, peritoneal bacteria content and intestinal lung and liver tissue samples of the CLP group. Hemavet changes and peritoneal inflammation findings were significantly limited in the CLP/T3 and CLP/MP/T3 groups. Histopathologic changes had no significant difference between the groups during an early sepsis. Compared to the MP replacement therapy, therapeutic effects of T3 replacement therapy have been found significantly more promising (Tab. 1, Fig. 10, Ref. 49).

Blood-Based Biomarkers of Early-Onset Breast Cancer

DTIC Science & Technology

2015-10-01

n=51). The women with early-onset breast cancer were disease and treatment free for at least 6 months at time of blood donation . Cases and controls...were age matched to age at blood donation . 2. KEYWORDS: biomarkers, early-onset breast cancer, expression profiling, risk-assessment, breast cancer...matched controls. This prospectively collected cohort consists of blood donated to blood banks ~15 years ago and subsequently linked to the California

Bilirubin exposure is associated with neonatal sepsis in the eight days preceding symptoms: a retrospective study.

PubMed

Raimondi, Francesco; Borrelli, Angela Carla; Ferrara, Teresa; Giannattasio, Antonietta; Capasso, Letizia

2017-09-01

To compare levels of bilirubin (using the area under the curve, AUC) in preterm infants before the onset of sepsis with healthy matched-controls. Preterm infants born between January 2011 and December 2015 with late-onset sepsis were enrolled in our retrospective study and were matched with healthy controls (sex, birth weight and gestational age). Levels of bilirubin were registered in the eight days preceding the onset of sepsis and the AUC was calculated for both groups. Eighty-eight neonates (44 cases) were studied. GA and BW did not differ between cases and controls. In cases, we found a higher value of AUC (30.7 versus 22.5; p = 0.021). In our retrospective cohort, we found that the levels of bilirubin and the AUC in the first eight days before the onset of sepsis in preterm infants were significantly higher than the healthy controls. These data suggest that the prolonged exposition to high levels of bilirubin could increase the infection susceptibility in preterm infants.

[Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

PubMed

Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

2016-07-01

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

Early childhood predictors of early onset of smoking: a birth prospective study.

PubMed

Hayatbakhsh, Reza; Mamun, Abdullah A; Williams, Gail M; O'Callaghan, Michael J; Najman, Jake M

2013-10-01

Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes. This study aimed to examine early life predictors of onset of smoking in an Australian young cohort. Data were from the Mater Hospital and University of Queensland Study of Pregnancy (MUSP), a population-based prospective birth cohort study (1981-2012). The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up. Of these, data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study. Of 3714 young adults, 49.6% (49.9% males and 49.3% females) reported having ever smoked cigarettes. For those who had ever smoked, mean and median ages at first smoke were 15.5 and 16.0years, respectively. In multivariate Cox proportional hazard analysis mother's education, change in maternal marital status, maternal cigarette smoking and alcohol consumption, maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking. The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age. Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pasteurization of mother's own milk for preterm infants does not reduce the incidence of late-onset sepsis.

PubMed

Cossey, Veerle; Vanhole, Chris; Eerdekens, An; Rayyan, Maissa; Fieuws, Steffen; Schuermans, Annette

2013-01-01

Feeding preterm infants human milk has a beneficial effect on the risk of late-onset sepsis (LOS). Due to lack of microbiological standards, practices such as pasteurization of mother's own milk differ widely among neonatal intensive care units worldwide. To investigate whether pasteurization of mother's own milk for very-low-birth-weight (VLBW) infants influences the incidence and severity of infection-related outcomes. In this randomized controlled trial, preterm infants (gestational age <32 weeks and/or birth weight <1,500 g) received either raw or pasteurized mother's own milk during the first 8 weeks of life. The primary outcome was the incidence of proven LOS. A dose-response relation was verified, i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother's own milk. This study included 303 VLBW infants (mean birth weight: 1,276 g; mean gestational age: 29 weeks) whose baseline and nutritional characteristics were similar. The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk: 22/151 (0.15, CI: 0.08-0.20) and 31/152 (0.20, CI: 0.14-0.27), respectively (RR: 0.71; 95% CI: 0.43-1.17). A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS, regardless of the type of feeding. For preterm infants, pasteurization of mother's own milk shows a trend towards an increase in infectious morbidity, although no statistical significance was reached. Practices should focus on collection, storage and labeling procedures to ensure the safety and quality of expressed milk. Copyright © 2012 S. Karger AG, Basel.

Intraspinal anomalies in early-onset idiopathic scoliosis.

PubMed

Pereira, E A C; Oxenham, M; Lam, K S

2017-06-01

In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice

PubMed Central

Wang, Xianfeng; Buechler, Nancy L.; Martin, Ayana; Wells, Jonathan; Yoza, Barbara; McCall, Charles E.; Vachharajani, Vidula

2016-01-01

Objective Obesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis. Methods Sepsis was induced using cecal ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a “second-hit” (marker of immune function) at different time points to track phases of sepsis in ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis. Results We observed that the ob/ob-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in ob/ob mice during hypo-inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation in vivo via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65. Conclusion SIRT-2 regulates microvascular inflammation in obese mice with sepsis and may

Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival.

PubMed

Craciun, Florin L; Schuller, Elizabeth R; Remick, Daniel G

2010-12-01

Neutrophils are critical for the rapid eradication of bacterial pathogens, but they also contribute to the development of multiple organ failure in sepsis. We hypothesized that increasing early recruitment of neutrophils to the focus of infection will increase bacterial clearance and improve survival. Sepsis was induced in mice, using cecal ligation and puncture (CLP); blood samples were collected at 6 and 24 h; and survival was followed for 28 d. In separate experiments, peritoneal bacteria and inflammatory cells were measured. Septic mice predicted to die based on IL-6 levels (Die-P) had higher concentrations of CXCL1 and CXCL2 in the peritoneum and plasma compared with those predicted to live (Live-P). At 6 h, Live-P and Die-P had equivalent numbers of peritoneal neutrophils and bacteria. In Die-P mice the number of peritoneal bacteria increased between 6 and 24 h post-CLP, whereas in Live-P it decreased. The i.p. injection of CXCL1 and CXCL2 in naive mice resulted in local neutrophil recruitment. When given immediately after CLP, CXC chemokines increased peritoneal neutrophil recruitment at 6 h after CLP. This early increase in neutrophils induced by exogenous chemokines resulted in significantly fewer peritoneal bacteria by 24 h [CFU (log) = 6.04 versus 4.99 for vehicle versus chemokine treatment; p < 0.05]. Chemokine treatment significantly improved survival at both 5 d (40 versus 72%) and 28 d (27 versus 52%; p < 0.02 vehicle versus chemokines). These data demonstrate that early, local treatment with CXC chemokines enhances neutrophil recruitment and clearance of bacteria as well as improves survival in the CLP model of sepsis.

Genetics Home Reference: early-onset glaucoma

MedlinePlus

... called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma. Other individuals experience early onset of primary open-angle glaucoma, the most ...

Biomarkers of sepsis

PubMed Central

2013-01-01

Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year prospective study.

PubMed

Hammoud, Majeda S; Al-Taiar, Abdullah; Thalib, Lukman; Al-Sweih, Noura; Pathan, Seema; Isaacs, David

2012-07-01

Investigate the incidence, etiological pattern and the antimicrobial resistance of late-onset neonatal infections over a period of 5 years. Longitudinal audit of neonatal sepsis from January 2005 to December 2009, in the main maternity hospital in Kuwait. Late-onset neonatal infection was defined as the culture of a single potentially pathogenic organism from blood or cerebrospinal fluid from an infant older than 6 days in association with clinical or laboratory findings consistent with infection. The overall incidence was 16.9 (95% confidence interval: 15.8-18.0) episodes per 1000 live births. The commonest pathogen was coagulase-negative Staphylococcus, 339 (35.7%), while Klebsiella was the most common gram-negative infection, 178 (18.8%). Escherichia coli, Enterococcus and Enterobacter spp were each responsible for 6% of all infections. Candida caused 104 (11.0%) infections. The general pattern of infection remained unchanged over the study period. Case fatality was 11.7% (95% confidence interval: 9.7-13.9%) and was high for Pseudomonas (18.4%) and Candida (22.1%) infections. Approximately 24 and 20% of Klebsiella infections were resistant to cefotaxime and gentamicin, respectively, while 28 and 24% of Escherichia coli infections were resistant to cefotaxime and gentamicin, respectively. The incidence of late-onset infection in Kuwait is high, resembling that in resource-poor countries. The high incidence coupled with low case fatality provides an example for settings where tertiary care is introduced without strict measures against nosocomial infections. Prevention against nosocomial infections in neonatal units has the potential to further reduce neonatal mortality in these settings. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status.

PubMed

Léger, Thibault; Charrier, Alice; Moreau, Clarisse; Hininger-Favier, Isabelle; Mourmoura, Evangelia; Rigaudière, Jean-Paul; Pitois, Elodie; Bouvier, Damien; Sapin, Vincent; Pereira, Bruno; Azarnoush, Kasra; Demaison, Luc

2017-07-01

If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll-like receptor-9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF- α and IL-1 β In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham-operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF- α and gene expression of IL-1 β and TNF- α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF- α and IL-1 β on the cardiac function is known to occur at very high concentrations. The influence of low- to moderate-grade inflammation on the myocardial mechanical behavior must thus be revisited. © 2017 French National Institute of Agronomical Research (INRA). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients.

PubMed

Snowsill, Tristan; Huxley, Nicola; Hoyle, Martin; Jones-Hughes, Tracey; Coelho, Helen; Cooper, Chris; Frayling, Ian; Hyde, Chris

2015-04-25

Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost-utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could outweigh

Early onset obsessive-compulsive disorder with and without tics.

PubMed

de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

2009-07-01

Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

PubMed

Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

2010-08-01

The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

The Novel Immunotherapeutic Oligodeoxynucleotide IMT504 Protects Neutropenic Animals from Fatal Pseudomonas aeruginosa Bacteremia and Sepsis

PubMed Central

Chahin, Abdullah; Zorzopulos, Jorge; Jobes, David V.; Migdady, Yazan; Yamamoto, Michelle; Parejo, Nicholas; Palardy, John E.; Horn, David L.

2014-01-01

IMT504 is a novel immunomodulatory oligonucleotide that has shown immunotherapeutic properties in early preclinical and clinical studies. IMT504 was tested in a neutropenic rat model of Pseudomonas aeruginosa bacteremia and sepsis. This animal system recapitulates many of the pathological processes found in neutropenic patients with Gram-negative, bacterial infections. The research was conducted in the setting of an academic research laboratory. The test subjects were Sprague-Dawley rats. Animals were rendered neutropenic by administration of cyclophosphamide, colonized with P. aeruginosa by oral feeding, and then randomized to receive IMT504 over a range of doses and treatment regimens representing early and late therapeutic interventions. IMT504 immunotherapy conferred a significant survival advantage over the 12-day study period compared with the results seen with placebo-treated animals when the therapy was administered at the onset of neutropenia and even in the absence of antibiotics and after the onset of fever and systemic infection. Notably, even late salvage IMT504 monotherapy was highly effective (13/14 surviving rats with IMT504 therapy versus 2/14 controls, P = <0.001). Moreover, late salvage IMT504 monotherapy was as effective as antibiotic therapy (13/14 surviving rats versus 21/21 rats, P = 0.88). In addition, no antagonism or loss of therapeutic efficacy was noted with combination therapy of IMT504 plus antibiotics. IMT504 immunotherapy provides a remarkable survival advantage in bacteremia and sepsis in neutropenic animals and deserves further study as a new treatment option in patients with, or at risk for, severe Gram-negative bacterial infections and sepsis. PMID:25512413

Kocuria kristinae-caused sepsis in an infant with congenital tufting enteropathy.

PubMed

Aydin, Malik; Ganschow, Rainer; Jankofsky, Martin

2017-01-01

Aydin M, Ganschow R, Jankofsky M. Kocuria kristinae-caused sepsis in an infant with congenital tufting enteropathy. Turk J Pediatr 2017; 59: 93-96. Congenital tufting enteropathy (CTE) is characterized by the early-onset of chronic diarrhea and the inability to develop. It is a rare congenital disease with a low prevalence of 1:50,000 - 100,000 live births p.a. The histopathology is characterized by villous atrophy and the characteristic epithelial tufts. Recent identification of causative mutations in EpCAM has enhanced our understanding of this disease. Due to its severe clinical course, patients are dependent on parenteral nutrition to thrive successfully. Catheter-associated blood stream infections have become the primary problem for pediatric patients. Infections with Kocuria kristinae are rare. This report is about a 3-month-old girl with CTE suffering from a central venous catheter related mono-sepsis by K. kristinae. A sepsis therapy with meropenem and vancomycin improved her general state rapidly. Only few cases in the literature with CTE and K. kristinae are described. To the best of our knowledge, this is the first report presenting two coincidences in one case.

Early Onset Obesity and Risk of Metabolic Syndrome Among Chilean Adolescents

PubMed Central

Pacheco, Lorena Sonia; Blanco, Estela; Burrows, Raquel; Reyes, Marcela; Lozoff, Betsy

2017-01-01

Introduction Obesity and metabolic syndrome (MetS) indicators have increased globally among the pediatric population. MetS indicators in the young elevate their risk of cardiovascular disease and metabolic disorders later in life. This study examined early onset obesity as a risk factor for MetS risk in adolescence. Methods A cohort of Chilean participants (N = 673) followed from infancy was assessed at age 5 years and in adolescence (mean age, 16.8 y). Adiposity was measured at both time points; blood pressure and fasting blood samples were assessed in adolescence only. Early onset obesity was defined as a World Health Organization z score of 2 standard deviations (SDs) or more for body mass index (BMI) at age 5 years. We used linear regression to examine the association between early onset obesity and adolescent MetS risk z score, adjusting for covariates. Results Eighteen percent of participants had early onset obesity, and 50% of these remained obese in adolescence. Mean MetS risk z score in adolescence was significantly higher among those with early onset obesity than among those without (1.0; SD, 0.8 vs 0.2; SD, 0.8 [P < .001]). In the multivariable model, early onset obesity independently contributed to a higher MetS risk score in adolescence (β = 0.27, P < .001), controlling for obesity status at adolescence and sex, and explained 39% of the variance in MetS risk. Conclusion Early onset obesity as young as age 5 years relates to higher MetS risk. PMID:29023232

Improving Outcomes in Patients With Sepsis.

PubMed

Armen, Scott B; Freer, Carol V; Showalter, John W; Crook, Tonya; Whitener, Cynthia J; West, Cheri; Terndrup, Thomas E; Grifasi, Marissa; DeFlitch, Christopher J; Hollenbeak, Christopher S

2016-01-01

Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. © The Author(s) 2014.

Improving Outcomes in Patients With Sepsis

PubMed Central

Armen, Scott B.; Freer, Carol V.; Showalter, John W.; Crook, Tonya; Whitener, Cynthia J.; West, Cheri; Terndrup, Thomas E.; Grifasi, Marissa; DeFlitch, Christopher J.; Hollenbeak, Christopher S.

2017-01-01

Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = −1.98 to −0.16), 2.15 fewer hospital days (95% CI = −3.45 to −0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. PMID:25216849

Bacteriological profile of neonatal sepsis in a secondary care hospital in rural Tamil Nadu, Southern India.

PubMed

Pavan Kumar, Doniparthi Venkata; Mohan, Jesinth; Rakesh, P S; Prasad, Jasmine; Joseph, Lenikumar

2017-01-01

Neonatal sepsis is a leading cause of neonatal mortality and morbidity in the world. The objective of the current study was to detect the common causative microorganisms of neonatal sepsis and their antimicrobial resistance patterns in a rural secondary hospital in Tamil Nadu, India. Neonates (0-28 days) admitted to this newborn care unit from October 2013 to September 2015, with a diagnosis of probable sepsis were studied. All the enrolled babies had blood cultures taken and were followed up till final outcome, which was discharge or death, irrespective of culture result. Univariate analysis was performed for factors associated with culture positivity, generating odds ratios, and confidence intervals. Among the 107 babies with a diagnosis of probable sepsis, 28 (26.2%) had shown bacteria in culture. The majority (94.4%) were of early-onset sepsis. The predominant organisms were Staphylococcus aureus (10/28) and Klebsiella (6/28). 100% of Gram-negative bacilli and 90% of Staphylococcus were resistant to Ampicillin. Gentamicin resistance among Gram-negative bacilli and Staphylococcus was 52.9% and 20%, respectively, while third-generation cephalosporin resistance was 31.2% and 20%, respectively. Among the neonates diagnosed as probable sepsis, idiopathic prematurity ( P = 0.007) was found to have a statistically significant association with culture-positive sepsis. The culture positivity rate among the neonates with probable sepsis in the current study was 26%. An alarmingly high degree of antibiotic resistance observed calls for robust infection control practices and an urgent evaluation and development of individual and national antibiotic policies for neonatal sepsis.

Computerised sepsis protocol management. Description of an early warning system.

PubMed

de Dios, Begoña; Borges, Marcio; Smith, Timothy D; Del Castillo, Alberto; Socias, Antonia; Gutiérrez, Leticia; Nicolás, Jordi; Lladó, Bartolomé; Roche, Jose A; Díaz, Maria P; Lladó, Yolanda

2018-02-01

New strategies need to be developed for the early recognition and rapid response for the management of sepsis. To achieve this purpose, the Multidisciplinary Sepsis Team (MST) developed the Computerised Sepsis Protocol Management (PIMIS). The aim of this study was to evaluate the convenience of using PIMIS, as well as the activity of the MST. An analysis was performed on the data collected from solicited MST consultations (direct activation of PIMIS by attending physician or telephone request) and unsolicited ones (by referral from the microbiology laboratory or an automatic referral via the hospital vital signs recording software [SIDCV]), as well as the hospital department, source of infection, treatment recommendation, and acceptance of this. Of the 1,581 first consultations, 65.1% were solicited consultations (84.1% activation of PIMIS and 15.9% by telephone). The majority of unsolicited consultations were generated by the microbiology laboratory (95.2%), and 4.8% from the SIDCV. Referral from solicited consultations were generated sooner (5.63days vs 8.47days; P<.001) and came from clinical specialties rather than from the surgical ward (73.0% vs 39.1%; P<.001). A recommendation was made for antimicrobial prescription change in 32% of first consultations. The treating physician accepted 78.1% of recommendations. The high rate of solicited consultations and acceptance of recommended prescription changes suggest that a MST is seen as a helpful resource, and that PIMIS software is perceived to be useful and convenient to use, as it is the main source of referral. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Early Onset Recurrent Subtype of Adolescent Depression: Clinical and Psychosocial Correlates

ERIC Educational Resources Information Center

Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Herr, Nathaniel R.

2008-01-01

Background: Evaluated trajectories of adolescent depression and their correlates in a longitudinal study of a community sample: early onset (by age 15) with major depression (MDE) recurrence between 15 and 20; early onset with no recurrence; later onset of major depression after age 15 with and without recurrence by 20; and never-depressed.…

Early onset marijuana use is associated with learning inefficiencies.

PubMed

Schuster, Randi Melissa; Hoeppner, Susanne S; Evins, A Eden; Gilman, Jodi M

2016-05-01

Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Forty-eight young adults, aged 18-25, who used marijuana at least once per week and 48 matched nonusing controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: early onset users (EMJ), who started using marijuana at or before age 16 (n = 27), and late onset marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

ClinicalTrials.gov

2017-05-11

Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

Early intervention for late-onset ornithine transcarbamylase deficiency.

PubMed

Fujisawa, Daisuke; Mitsubuchi, Hiroshi; Matsumoto, Shirou; Iwai, Masanori; Nakamura, Kimitoshi; Hoshide, Ryuji; Harada, Nawomi; Yoshino, Makoto; Endo, Fumio

2015-01-01

We report the case of a family with late-onset ornithine transcarbamylase deficiency (OTCD). Several family members had died from OTCD, and the c.221G>A, p.Lys221Lys mutation was detected at the 3' end of exon 6 of OTC in the X-chromosome of some members. We provided genetic counseling on pregnancy, delivery, and neonate management to a 4th-generation female carrier and decided on metabolic management of her child from birth. Two male patients were diagnosed with late-onset OTCD on the basis of blood amino acid and genetic analysis, and they received arginine supplementation from the asymptomatic, early neonatal period. These children grew and developed normally, without decompensation. Patients with late-onset OTCD can and should be diagnosed and treated in the early neonatal period, especially those from families already diagnosed with late-onset OTCD, and family members must be provided with genetic counseling. © 2015 Japan Pediatric Society.

The Effect of Sepsis on the Erythrocyte

PubMed Central

Bateman, Ryon M.; Sharpe, Michael D.; Singer, Mervyn; Ellis, Christopher G.

2017-01-01

Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin’s affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O2-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction. PMID:28885563

The Effect of Sepsis on the Erythrocyte.

PubMed

Bateman, Ryon M; Sharpe, Michael D; Singer, Mervyn; Ellis, Christopher G

2017-09-08

Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin's affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca 2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O₂-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

PubMed Central

Arango, Celso

2014-01-01

Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

PubMed

Thomas, Benjamin S; Jafarzadeh, S Reza; Warren, David K; McCormick, Sandra; Fraser, Victoria J; Marschall, Jonas

2015-11-24

Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop

Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus.

PubMed

Wu, I-Hsyuan; Tsai, Ming-Horng; Lai, Mei-Yin; Hsu, Lee-Fen; Chiang, Ming-Chou; Lien, Reyin; Fu, Ren-Huei; Huang, Hsuan-Rong; Chu, Shih-Ming; Hsu, Jen-Fu

2017-07-03

Neonatal bloodstream infection (BSI) is the most important cause of morbidity and mortality in the neonatal intensive care unit (NICU). Although most neonatal BSIs are primary bacteremia, some are associated with a focus of infection. This distinction is not well characterized. All patients with neonatal late-onset sepsis (LOS) between January 2006 and December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus of infection if LOS occurred before or within 24 h after the diagnosis of a specific infectious entity, and as "primary bacteremia" if no concurrent focus of infection was identified. Data concerning demographics, hospital course, microbiology, and outcomes were compared via univariate and multivariate analyses. Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia, whereas 167 (17.6%) were associated with a known focus of infection, including meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%), catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis (NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all meningitis cases (29.4%). Although sepsis-attributable mortality was comparable between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs with meningitis, VAP, and NEC had significantly higher rates of infectious complications. The independent risk factors of sepsis-attributable mortality were infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40 and 7.40; 95% CI 1.21-4.74 and 3.70-14.78, P = 0.012 and <0.001, respectively); and underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91-11.96, P = 0.001). A considerable proportion of neonatal LOS can be associated with known

Factors associated with inter-institutional variations in sepsis rates of very-low-birth-weight infants in 34 Malaysian neonatal intensive care units.

PubMed

Boo, Nem-Yun; Cheah, Irene Guat-Sim

2016-03-01

This study aimed to determine whether patient loads, infant status on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis rates in very-low-birth-weight (VLBW) infants in the Malaysian National Neonatal Registry (MNNR). This was a retrospective study of 3,880 VLBW (≤ 1,500 g) infants admitted to 34 neonatal intensive care units (NICUs) in the MNNR. Sepsis was diagnosed in symptomatic infants with positive blood culture. Sepsis developed in 623 (16.1%) infants; 61 (9.8%) had early-onset sepsis (EOS) and 562 (90.2%) had late-onset sepsis (LOS). The median EOS rate of all NICUs was 1.0% (interquartile range [IQR] 0%, 2.0%). Compared with NICUs reporting no EOS (n = 14), NICUs reporting EOS (n = 20) had significantly higher patient loads (total live births, admissions, VLBW infants, outborns); more mothers with a history of abortions, and antenatal steroids and intrapartum antibiotic use; more infants requiring resuscitation procedures at birth; higher rates of surfactant therapy, pneumonia and insertion of central venous catheters. The median LOS rate of all NICUs was 14.5% (IQR 7.8%, 19.2%). Compared with NICUs with LOS rates below the first quartile (n = 8), those above the third quartile (n = 8) used less intrapartum antibiotics, and had significantly bigger and more mature infants, more outborns, as well as a higher number of sick infants requiring ventilator support and total parenteral nutrition. Patient loads, resuscitation at birth, status of infants on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis. Copyright: © Singapore Medical Association.

The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die.

PubMed

Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer

2017-09-01

The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies

Sepsis in general surgery: a deadly complication.

PubMed

Moore, Laura J; Moore, Frederick A; Jones, Stephen L; Xu, Jiaqiong; Bass, Barbara L

2009-12-01

Sepsis is a deadly and potentially preventable complication. A better understanding of sepsis in general surgery patients is needed to help direct resources to those patients at highest risk for death from sepsis. We identified risk factors for sepsis in general surgery patients by using the National Surgical Quality Improvement Project database. Analysis of the database identified 3 major risk factors for both the development of sepsis and death from sepsis in general surgery patients. These risk factors are age older than 60 years, need for emergency surgery, and the presence of comorbid conditions. Risk factors for death from sepsis or septic shock in general surgery patients include age older than 60 years, need for emergency surgery, and the presence of preexisting comorbidities. These findings emphasize the need for early recognition through aggressive sepsis screening and rapid implementation of evidence-based interventions for sepsis and septic shock in general surgery patients with these risk factors.

Systemic inflammatory response syndrome-based severe sepsis screening algorithms in emergency department patients with suspected sepsis.

PubMed

Shetty, Amith L; Brown, Tristam; Booth, Tarra; Van, Kim Linh; Dor-Shiffer, Daphna E; Vaghasiya, Milan R; Eccleston, Cassanne E; Iredell, Jonathan

2016-06-01

Systemic inflammatory response syndrome (SIRS)-based severe sepsis screening algorithms have been utilised in stratification and initiation of early broad spectrum antibiotics for patients presenting to EDs with suspected sepsis. We aimed to investigate the performance of some of these algorithms on a cohort of suspected sepsis patients. We conducted a retrospective analysis on an ED-based prospective sepsis registry at a tertiary Sydney hospital, Australia. Definitions for sepsis were based on the 2012 Surviving Sepsis Campaign guidelines. Numerical values for SIRS criteria and ED investigation results were recorded at the trigger of sepsis pathway on the registry. Performance of specific SIRS-based screening algorithms at sites from USA, Canada, UK, Australia and Ireland health institutions were investigated. Severe sepsis screening algorithms' performance was measured on 747 patients presenting with suspected sepsis (401 with severe sepsis, prevalence 53.7%). Sensitivity and specificity of algorithms to flag severe sepsis ranged from 20.2% (95% CI 16.4-24.5%) to 82.3% (95% CI 78.2-85.9%) and 57.8% (95% CI 52.4-63.1%) to 94.8% (95% CI 91.9-96.9%), respectively. Variations in SIRS values between uncomplicated and severe sepsis cohorts were only minor, except a higher mean lactate (>1.6 mmol/L, P < 0.01). We found the Ireland and JFK Medical Center sepsis algorithms performed modestly in stratifying suspected sepsis patients into high-risk groups. Algorithms with lactate levels thresholds of >2 mmol/L rather than >4 mmol/L performed better. ED sepsis registry-based characterisation of patients may help further refine sepsis definitions of the future. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Differentiating early-onset persistent versus childhood-limited conduct problem youth.

PubMed

Barker, Edward D; Maughan, Barbara

2009-08-01

Among young children who demonstrate high levels of conduct problems, less than 50% will continue to exhibit these problems into adolescence. Such developmental heterogeneity presents a serious challenge for intervention and diagnostic screening in early childhood. The purpose of the present study was to inform diagnostic screening and preventive intervention efforts by identifying youths whose conduct problems persist. The authors examined 1) the extent to which early-onset persistent versus childhood-limited trajectories can be identified from repeated assessments of childhood and early-adolescent conduct problems and 2) how prenatal and early postnatal risks differentiate these two groups. To identify heterogeneity in early-onset conduct problems, the authors used data from a large longitudinal population-based cohort of children followed from the prenatal period to age 13. Predictive risk factors examined were prenatal and postnatal measures of maternal distress (anxiety, depression), emotional and practical support, and family and child characteristics (from birth to 4 years of age). Findings revealed a distinction between early-onset persistent versus childhood-limited conduct problems in youths. Robust predictors of the early-onset persistent trajectory were maternal anxiety during pregnancy (32 weeks gestation), partner cruelty to the mother (from age 0 to 4 years), harsh parenting, and higher levels of child undercontrolled temperament. Sex differences in these risks were not identified. Interventions aiming to reduce childhood conduct problems should address prenatal risks in mothers and early postnatal risks in both mothers and their young children.

Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

PubMed Central

Vyas, Nora S.; Gogtay, Nitin

2012-01-01

Early onset schizophrenia (onset before adulthood) is a rare, severe, and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment-refractory cases. Based on the current literature, second-generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies. PMID:22485097

The Timing of Early Antibiotics and Hospital Mortality in Sepsis.

PubMed

Liu, Vincent X; Fielding-Singh, Vikram; Greene, John D; Baker, Jennifer M; Iwashyna, Theodore J; Bhattacharya, Jay; Escobar, Gabriel J

2017-10-01

Prior sepsis studies evaluating antibiotic timing have shown mixed results. To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

[Mutations of amyloid precursor protein in early-onset familial Alzheimer's disease].

PubMed

Naruse, S; Tsuji, S; Miyatake, T

1992-09-01

Genetic linkage studies of familial Alzheimer's disease (FAD) have suggested that some form of early-onset FAD is linked to proximal long arm of chromosome 21. It has been also suggested that some form of late-onset FAD is linked to long arm of chromosome 19. Goate et al have identified a mis-sense mutation (Val to Ile) in exon 17 of the amyloid precursor protein (APP) gene in 2 of 16 early-onset FAD families, and have shown that the FAD locus in an FAD family is tightly linked to the mis-sense mutation. To determine if the mis-sense mutation is observed in different ethnic origine, we have studied some early-onset FAD families. Two early-onset FAD families showed the existence of the mutation. As the mutation has been identified in different ethnic origine and the mutation has not been observed in normal individuals, it strengthen hypothesis that the mutation is pathogenic. Recently, Val to Phe and Val to Gly mutations have been also identified at the same codon (Codon 717) of the APP gene.

Evaluation of the novel respiratory virus surveillance program: Pediatric Early Warning Sentinel Surveillance (PEWSS).

PubMed

Armour, Patricia A; Nguyen, Linh M; Lutman, Michelle L; Middaugh, John P

2013-01-01

Infections caused by respiratory viruses are associated with recurrent epidemics and widespread morbidity and mortality. Routine surveillance of these pathogens is necessary to determine virus activity, monitor for changes in circulating strains, and plan for public health preparedness. The Southern Nevada Health District in Las Vegas, Nevada, recruited five pediatric medical practices to serve as sentinel sites for the Pediatric Early Warning Sentinel Surveillance (PEWSS) program. Sentinel staff collected specimens throughout the year from ill children who met the influenza-like illness case definition and submitted specimens to the Southern Nevada Public Health Laboratory for molecular testing for influenza and six non-influenza viruses. Laboratory results were analyzed and reported to the medical and general communities in weekly bulletins year-round. PEWSS data were also used to establish viral respiratory seasonal baselines and in influenza vaccination campaigns. The surveillance program was evaluated using the Centers for Disease Control and Prevention's (CDC's) Updated Guidelines for Evaluating Public Health Surveillance Systems. PEWSS met three of six program usefulness criteria and seven of nine surveillance system attributes, which exceeded the CDC Guidelines evaluation criteria for a useful and complete public health surveillance program. We found that PEWSS is a useful and complete public health surveillance system that is simple, flexible, accessible, and stable.

An Evidence Based Approach to Sepsis: Educational Program

ERIC Educational Resources Information Center

Perez, Dolores

2015-01-01

Evidence-based guidelines for recognizing and treating sepsis have been available for decades, yet healthcare providers do not adhere to the recommendations. Sepsis can progress rapidly if not recognized early. Literature reports reveal that sepsis is the leading cause of death in non-cardiac intensive care units (ICUs), and it is one of the most…

Genetic Determinism of Primary Early-Onset Osteoarthritis.

PubMed

Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

2016-01-01

Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Co-Occurring Problems of Early Onset Persistent, Childhood Limited, and Adolescent Onset Conduct Problem Youth

ERIC Educational Resources Information Center

Barker, Edward D.; Oliver, Bonamy R.; Maughan, Barbara

2010-01-01

Background: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems…

A Review of GM-CSF Therapy in Sepsis

PubMed Central

Mathias, Brittany; Szpila, Benjamin E.; Moore, Frederick A.; Efron, Philip A.; Moldawer, Lyle L.

2015-01-01

Abstract Determine what clinical role, if any, GM-CSF may have in the clinical treatment of sepsis in the adult patient. Advancements in the management of sepsis have led to significant decreases in early mortality; however, sepsis remains a significant source of long-term mortality and disability which places strain on healthcare resources with a substantial growing economic impact. Historically, early multiple organ failure (MOF) and death in patients with severe sepsis was thought to result from an exaggerated proinflammatory response called the systemic inflammatory response syndrome (SIRS). Numerous prospective randomized controlled trials (PRCTs) tested therapies aimed at decreasing the organ injury associated with an exaggerated inflammatory response. With few exceptions, the results from these PRCTs have been disappointing, and currently no specific therapeutic agent is approved to counteract the early SIRS response in patients with severe sepsis. It has long been recognized that there is a delayed immunosuppressive state that contributes to long-term morbidity. However, recent findings now support a concurrent proinflammatory and anti-inflammatory response present throughout sepsis. Multiple immunomodulating agents have been studied to combat the immunosuppressive phase of sepsis with the goal of decreasing secondary infection, reducing organ dysfunction, decreasing ICU stays, and improving survival. Granulocyte-macrophage colony stimulating factor (GM-CSF), a myelopoietic growth factor currently used in patients with neutropenia secondary to chemotherapy-induced myelosuppression, has been studied as a potential immune-activating agent. The applicability of GM-CSF as a standard therapy for generalized sepsis is still largely understudied; however, small-scale studies available have demonstrated some improved recovery from infection, decreased hospital length of stay, decreased days requiring mechanical ventilation, and decreased medical costs. PMID

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

PubMed

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency.

PubMed

Peng, Kaiyue; Qian, Xiaowen; Huang, Zhiheng; Lu, Junping; Wang, Yuhuan; Zhou, Ying; Wang, Huijun; Wu, Bingbing; Wang, Ying; Chen, Lingli; Zhai, Xiaowen; Huang, Ying

2018-05-18

Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post-transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced-intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001.

Nursing considerations to complement the Surviving Sepsis Campaign guidelines.

PubMed

Aitken, Leanne M; Williams, Ged; Harvey, Maurene; Blot, Stijn; Kleinpell, Ruth; Labeau, Sonia; Marshall, Andrea; Ray-Barruel, Gillian; Moloney-Harmon, Patricia A; Robson, Wayne; Johnson, Alexander P; Lan, Pang Nguk; Ahrens, Tom

2011-07-01

To provide a series of recommendations based on the best available evidence to guide clinicians providing nursing care to patients with severe sepsis. Modified Delphi method involving international experts and key individuals in subgroup work and electronic-based discussion among the entire group to achieve consensus. We used the Surviving Sepsis Campaign guidelines as a framework to inform the structure and content of these guidelines. We used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system to rate the quality of evidence from high (A) to very low (D) and to determine the strength of recommendations, with grade 1 indicating clear benefit in the septic population and grade 2 indicating less confidence in the benefits in the septic population. In areas without complete agreement between all authors, a process of electronic discussion of all evidence was undertaken until consensus was reached. This process was conducted independently of any funding. Sixty-three recommendations relating to the nursing care of severe sepsis patients are made. Prevention recommendations relate to education, accountability, surveillance of nosocomial infections, hand hygiene, and prevention of respiratory, central line-related, surgical site, and urinary tract infections, whereas infection management recommendations related to both control of the infection source and transmission-based precautions. Recommendations related to initial resuscitation include improved recognition of the deteriorating patient, diagnosis of severe sepsis, seeking further assistance, and initiating early resuscitation measures. Important elements of hemodynamic support relate to improving both tissue oxygenation and macrocirculation. Recommendations related to supportive nursing care incorporate aspects of nutrition, mouth and eye care, and pressure ulcer prevention and management. Pediatric recommendations relate to the use of antibiotics, steroids, vasopressors and

Diagnosis and prognosis of early-onset intrahepatic cholestasis of pregnancy: a prospective study.

PubMed

Lin, Jing; Gu, Wei; Hou, Yanyan

2017-11-07

To explore the gestational age of early-onset intrahepatic cholestasis (ICP) of pregnancy, and to analyze the relationship between the clinical biochemical indices and pregnancy outcomes in order to arrive at a reasonable diagnosis and administer appropriate treatment. This is a retrospective clinical study. We selected 47,260 pregnant women who received prenatal care and underwent childbirth at the International Peace Maternity and Child Health Hospital affiliated to Shanghai Jiao Tong University from January 2014 to December 2016 for participating in this study. Of these 47,260 women, 407 developed ICP. To calculate the gestational week cutoff between early- and late-onset ICP by the receiver-operating characteristic (ROC) curve and Youden's index. Two independent samples t tests and chi square test were used to compare the differences in biochemical indices and pregnancy outcomes between the two groups. We found that 34 weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. Early-onset ICP is characterized by early onset, long disease duration and a higher incidence of preterm labor, fetal distress, and fetal low birth weight compared to late-onset ICP. Thirty-four weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. And to reduce the adverse pregnancy outcomes in cases of early-onset ICP, we suggest prolonging gestation up to 37 weeks as far as possible before selecting iatrogenic birth.

Specific Intellectual Deficits in Children with Early Onset Diabetes Mellitus.

ERIC Educational Resources Information Center

Rovet, Joanne F.; And Others

1988-01-01

Compares 27 children with early onset diabetes (EOD) with 24 children with late onset diabetes (LOD) and 30 sibling controls in performance on tests of intellectual functioning and school achievement. Results revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. (Author/RWB)

Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

PubMed

Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p < 0.001) were risk factors independently associated with early-onset peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p < 0.001) and worse technique survival (p < 0.001), while patient survival did not differ significantly between the 2 groups during the long-term follow-up (p > 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

Evaluation of the Novel Respiratory Virus Surveillance Program: Pediatric Early Warning Sentinel Surveillance (PEWSS)

PubMed Central

Nguyen, Linh M.; Lutman, Michelle L.; Middaugh, John P.

2013-01-01

Objectives Infections caused by respiratory viruses are associated with recurrent epidemics and widespread morbidity and mortality. Routine surveillance of these pathogens is necessary to determine virus activity, monitor for changes in circulating strains, and plan for public health preparedness. The Southern Nevada Health District in Las Vegas, Nevada, recruited five pediatric medical practices to serve as sentinel sites for the Pediatric Early Warning Sentinel Surveillance (PEWSS) program. Methods Sentinel staff collected specimens throughout the year from ill children who met the influenza-like illness case definition and submitted specimens to the Southern Nevada Public Health Laboratory for molecular testing for influenza and six non-influenza viruses. Results Laboratory results were analyzed and reported to the medical and general communities in weekly bulletins year-round. PEWSS data were also used to establish viral respiratory seasonal baselines and in influenza vaccination campaigns. The surveillance program was evaluated using the Centers for Disease Control and Prevention's (CDC's) Updated Guidelines for Evaluating Public Health Surveillance Systems. PEWSS met three of six program usefulness criteria and seven of nine surveillance system attributes, which exceeded the CDC Guidelines evaluation criteria for a useful and complete public health surveillance program. Conclusion We found that PEWSS is a useful and complete public health surveillance system that is simple, flexible, accessible, and stable. PMID:23997308

Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.

PubMed

Brown, Richard G; Marchesi, Julian R; Lee, Yun S; Smith, Ann; Lehne, Benjamin; Kindinger, Lindsay M; Terzidou, Vasso; Holmes, Elaine; Nicholson, Jeremy K; Bennett, Phillip R; MacIntyre, David A

2018-01-24

Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis

PubMed Central

Chan, Grace J.; Lee, Anne CC; Baqui, Abdullah H.; Tan, Jingwen; Black, Robert E.

2013-01-01

Background Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period. Methods and Findings We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors. Conclusions Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high

Factors associated with inter-institutional variations in sepsis rates of very-low-birth-weight infants in 34 Malaysian neonatal intensive care units

PubMed Central

Boo, Nem-Yun; Cheah, Irene Guat-Sim

2016-01-01

INTRODUCTION This study aimed to determine whether patient loads, infant status on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis rates in very-low-birth-weight (VLBW) infants in the Malaysian National Neonatal Registry (MNNR). METHODS This was a retrospective study of 3,880 VLBW (≤ 1,500 g) infants admitted to 34 neonatal intensive care units (NICUs) in the MNNR. Sepsis was diagnosed in symptomatic infants with positive blood culture. RESULTS Sepsis developed in 623 (16.1%) infants; 61 (9.8%) had early-onset sepsis (EOS) and 562 (90.2%) had late-onset sepsis (LOS). The median EOS rate of all NICUs was 1.0% (interquartile range [IQR] 0%, 2.0%). Compared with NICUs reporting no EOS (n = 14), NICUs reporting EOS (n = 20) had significantly higher patient loads (total live births, admissions, VLBW infants, outborns); more mothers with a history of abortions, and antenatal steroids and intrapartum antibiotic use; more infants requiring resuscitation procedures at birth; higher rates of surfactant therapy, pneumonia and insertion of central venous catheters. The median LOS rate of all NICUs was 14.5% (IQR 7.8%, 19.2%). Compared with NICUs with LOS rates below the first quartile (n = 8), those above the third quartile (n = 8) used less intrapartum antibiotics, and had significantly bigger and more mature infants, more outborns, as well as a higher number of sick infants requiring ventilator support and total parenteral nutrition. CONCLUSION Patient loads, resuscitation at birth, status of infants on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis. PMID:26996633

Surveillance and early warning systems of infectious disease in China: From 2012 to 2014.

PubMed

Zhang, Honglong; Wang, Liping; Lai, Shengjie; Li, Zhongjie; Sun, Qiao; Zhang, Peng

2017-07-01

Appropriate surveillance and early warning of infectious diseases have very useful roles in disease control and prevention. In 2004, China established the National Notifiable Infectious Disease Surveillance System and the Public Health Emergency Event Surveillance System to report disease surveillance and events on the basis of data sources from the National Notifiable Infectious Disease Surveillance System, China Infectious Disease Automated-alert and Response System in this country. This study provided a descriptive summary and a data analysis, from 2012 to 2014, of these 3 key surveillance and early warning systems of infectious disease in China with the intent to provide suggestions for system improvement and perfection. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of an emergency department electronic sepsis surveillance system on patient mortality and length of stay.

PubMed

Austrian, Jonathan S; Jamin, Catherine T; Doty, Glenn R; Blecker, Saul

2018-05-01

The purpose of this study was to determine whether an electronic health record-based sepsis alert system could improve quality of care and clinical outcomes for patients with sepsis. We performed a patient-level interrupted time series study of emergency department patients with severe sepsis or septic shock between January 2013 and April 2015. The intervention, introduced in February 2014, was a system of interruptive sepsis alerts triggered by abnormal vital signs or laboratory results. Primary outcomes were length of stay (LOS) and in-hospital mortality; other outcomes included time to first lactate and blood cultures prior to antibiotics. We also assessed sensitivity, positive predictive value (PPV), and clinician response to the alerts. Mean LOS for patients with sepsis decreased from 10.1 to 8.6 days (P < .001) following alert introduction. In adjusted time series analysis, the intervention was associated with a decreased LOS of 16% (95% CI, 5%-25%; P = .007, with significance of α = 0.006) and no change thereafter (0%; 95% CI, -2%, 2%). The sepsis alert system had no effect on mortality or other clinical or process measures. The intervention had a sensitivity of 80.4% and a PPV of 14.6%. Alerting based on simple laboratory and vital sign criteria was insufficient to improve sepsis outcomes. Alert fatigue due to the low PPV is likely the primary contributor to these results. A more sophisticated algorithm for sepsis identification is needed to improve outcomes.

Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

PubMed

Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

2017-07-01

This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p < 0.05). The rate of secondary hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p < 0.05). Obesity, waist circumference, and SHBG were significantly associated with serum total testosterone level in all, early-onset, and late-onset T2DM. Both all and early-onset T2DM groups had positive correlations between total testosterone and fasting C-peptide, total cholesterol, triglycerides, and uric acid. Our results indicate that in a population of admission to a large urban hospital in China, the prevalence of hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

PubMed

Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

2014-08-01

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

Whole Exome Analysis of Early Onset Alzheimer’s Disease

DTIC Science & Technology

2015-04-01

autosomal recessive early-onset Parkinson’s disease and juvenile Parkinson disease , Parkin has been shown to promote intracellular Abeta1–42 clearance [15... Parkinsonism . Conclusions Mutations were found in 6/50 families. The presence of an APOE-4 allele may account for disease status in one affected non...AD_________________ Award Number: W81XWH-12-1-0013 TITLE: Whole Exome Analysis of Early Onset Alzheimer’s Disease PRINCIPAL INVESTIGATOR

Are early-onset cannabis smokers at an increased risk of depression spells?

PubMed

Fairman, Brian J; Anthony, James C

2012-04-01

A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005-2009 (74-76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR=1.7 and 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk. Copyright © 2011

Are early-onset cannabis smokers at an increased risk of depression spells?

PubMed Central

Fairman, Brian J.; Anthony, James C.

2012-01-01

Background A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). Methods The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005–2009 (74–76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. Results About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR = 1.7 & 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Limitations Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Conclusion Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to

Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway

PubMed Central

Wang, Nian; Mao, Li; Yang, Liu; Zou, Jiang; Liu, Ke; Liu, Meidong; Zhang, Huali; Xiao, Xianzhong; Wang, Kangkai

2017-01-01

Resveratrol, a polyphenol compound derived from various edible plants, protects against sepsis-induced acute kidney injury (AKI) via its anti-inflammatory activity, but the underlying mechanisms remain largely unknown. In this study, a rat model of sepsis was established by cecal ligation and puncture (CLP), 30 mg/kg resveratrol was intraperitoneally administrated immediately after the CLP operation. HK-2 cells treated by 1 μg/ml lipopolysaccharide, 0.2 μM tunicamycin, 2.5 mM irestatin 9389 and 20 μM resveratrol were used for in vitro study. The results demonstrated that resveratrol significantly improved the renal function and tubular epithelial cell injury and enhanced the survival rate of CLP-induced rat model of sepsis, which was accompanied by a substantial decrease of the serum content and renal mRNA expressions of TNF-α, IL-1β and IL-6. In addition, resveratrol obviously relieved the endoplasmic reticulum stress, inhibited the phosphorylation of inositol-requiring enzyme 1(IRE1) and nuclear factor-κB (NF-κB) in the kidney. In vitro studies showed that resveratrol enhanced the cell viability, reduced the phosphorylation of NF-κB and production of inflammatory factors in lipopolysaccharide and tunicamycin-induced HK-2 cells through inhibiting IRE1 activation. Taken together, administration of resveratrol as soon as possible after the onset of sepsis could protect against septic AKI mainly through inhibiting IRE1-NF-κB pathway-triggered inflammatory response in the kidney. Resveratrol might be a readily translatable option to improve the prognosis of sepsis. PMID:28430592

Key goals and indicators for successful aging of adults with early-onset disability.

PubMed

LaPlante, Mitchell P

2014-01-01

Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and independence. However, indicators suggest that elevated risk factors for aging-related chronic diseases, including smoking, obesity, and inactivity, as well as barriers to prevention and the diminished social and economic situation of adults with disabilities are continuing impediments to successful aging that must be addressed. Increased provider awareness that people with early-onset disabilities are aging and can age successfully and the integration of disability and aging services systems are transformative steps that will help adults with early-onset disability to age more successfully. Copyright © 2014 Elsevier Inc. All rights reserved.

Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.

PubMed

Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapaporn; Sriussadaporn, Sutin; Vannaseang, Sathit; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

2009-06-01

Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes. Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations. We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands. Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.

[Clinical characteristics and renal uric acid excretion in early-onset gout patients].

PubMed

Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

2018-03-01

Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), P< 0.05], significantly higher serum UA level [(634±124)μmol/L vs.(527±169)μmol/L] and glomerular load of UA[(7.2±2.8)mg·min(-1)·1.73m(-2) vs. (4.4±2.2)mg·min(-1)·1.73m(-2)] and estimated glomerular filtration rate (GFR) [(83±21)ml·min(-1)·1.73m(-2) vs. (67±21)ml·min(-1)·1.73m(-2)] (all P< 0.05), lower fractional excretion of UA [4.4% (3.4%,6.1%) vs. 7.2% (5.2%,9.6%), P< 0.05], whereas 24h urinary UA excretion was comparable [(2 788±882)μmol/1.73m(2) vs. (2 645±1 140)μmol/1.73m(2), P= 0.274]. Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5%(3.3%,6.1%) vs. 6.7% (5.1%,8.7%), P< 0.05]. Logistic regression analysis showed that obesity ( OR= 3.25) and fractional excretion of UA less than 7% ( OR= 9.01, all P< 0.05) were risk factors of gout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

Staphylococcus aureus infections in Australasian neonatal nurseries.

PubMed

Isaacs, D; Fraser, S; Hogg, G; Li, H Y

2004-07-01

To study the incidence and outcome of systemic infections with methicillin sensitive (MSSA) and methicillin resistant Staphylococcus aureus (MRSA) infections in Australasian neonatal nurseries. Prospective longitudinal study of systemic infections (clinical sepsis plus positive cultures of blood and/or cerebrospinal fluid) in 17 Australasian neonatal nurseries. The incidence of early onset sepsis with S aureus, mainly MSSA, was 19 cases per 244 718 live births or 0.08 per 1000. From 1992 to 1994, MRSA infections caused only 8% of staphylococcal infections. From 1995 to 1998, there was an outbreak of MRSA infection, in two Melbourne hospitals. The outbreak resolved, after the use of topical mupirocin and improved handwashing. Babies with MRSA sepsis were significantly smaller than babies with MSSA sepsis (mean birth weight 1093 v 1617 g) and more preterm (mean gestation 27.5 v 30.3 weeks). The mortality of MRSA sepsis was 24.6% compared with 9.9% for MSSA infections. The mortality of early onset MSSA sepsis, however, was 39% (seven of 18) compared with 7.3% of late onset MSSA infection presenting more than two days after birth. S aureus is a rare but important cause of early onset sepsis. Late onset MRSA infections carried a higher mortality than late onset MSSA infections, but babies with early onset MSSA sepsis had a particularly high mortality.

Pediatric Sepsis Endotypes Among Adults With Sepsis.

PubMed

Wong, Hector R; Sweeney, Timothy E; Hart, Kimberly W; Khatri, Purvesh; Lindsell, Christopher J

2017-12-01

Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality. Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated. Multiple ICUs. Adults with sepsis. None. Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality. Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information.

Characterization of Early Partial Seizure Onset: Frequency, Complexity and Entropy

PubMed Central

Jouny, Christophe C.; Bergey, Gregory K.

2011-01-01

Objective A clear classification of partial seizures onset features is not yet established. Complexity and entropy have been very widely used to describe dynamical systems, but a systematic evaluation of these measures to characterize partial seizures has never been performed. Methods Eighteen different measures including power in frequency bands up to 300Hz, Gabor atom density (GAD), Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample entropy, and permutation entropy, were selected to test sensitivity to partial seizure onset. Intracranial recordings from forty-five patients with mesial temporal, neocortical temporal and neocortical extratemporal seizure foci were included (331 partial seizures). Results GAD, Lempel-Ziv complexity, HFD, high frequency activity, and sample entropy were the most reliable measures to assess early seizure onset. Conclusions Increases in complexity and occurrence of high-frequency components appear to be commonly associated with early stages of partial seizure evolution from all regions. The type of measure (frequency-based, complexity or entropy) does not predict the efficiency of the method to detect seizure onset. Significance Differences between measures such as GAD and HFD highlight the multimodal nature of partial seizure onsets. Improved methods for early seizure detection may be achieved from a better understanding of these underlying dynamics. PMID:21872526

Fever in sepsis.

PubMed

Schortgen, F

2012-11-01

Fever is a common symptom of sepsis usually believed to predict better survival. Experimental data suggest that body temperature elevation may slow micro-organism growth and enhance host immune responses. In patients with sepsis, however, the high energy cost of fever may exacerbate the life-threatening situation. Fever control is widely used in the ICU, mainly in patients with infections. The efficacy of antipyretic drugs in lowering body temperature remains uncertain, however, and all antipyretics have well known adverse effects. Surface cooling methods are efficient but require sedation to avoid the harmful effects of shivering. A recent controlled trial in patients with septic shock suggests that external cooling for fever control may diminish vasopressor requirements and improve early survival. In this review, we examine the benefits and risks of fever and of controlled normothermia. The fever control modalities that provide the best risk/benefit ratio in sepsis are discussed.

CDKL5 and ARX mutations in males with early-onset epilepsy.

PubMed

Mirzaa, Ghayda M; Paciorkowski, Alex R; Marsh, Eric D; Berry-Kravis, Elizabeth M; Medne, Livija; Alkhateeb, Asem; Grix, Art; Wirrell, Elaine C; Powell, Berkley R; Nickels, Katherine C; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B; Das, Soma

2013-05-01

Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. Although numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only 10 males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging, and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. These 18 patients include eight new males with CDKL5 mutations and 10 with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large dataset therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy in boys. Copyright © 2013 Elsevier Inc. All rights reserved.

CDKL5 and ARX mutations in males with early-onset epilepsy

PubMed Central

Mirzaa, Ghayda M.; Paciorkowski, Alex R.; Marsh, Eric D.; Berry-Kravis, Elizabeth M.; Medne, Livija; Grix, Art; Wirrell, Elaine C.; Powell, Berkley R.; Nickels, Katherine C.; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B.; Das, Soma

2013-01-01

Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. While numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only ten males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. The 18 patients include eight new males with CDKL5 mutations and ten with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large data set therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy. PMID:23583054

Early onset dementia in New Zealand Pacific boxers: a case series.

PubMed

Payman, Vahid; Yates, Susan; Cullum, Sarah

2018-05-04

To describe the biopsychosocial characteristics of a series of Pacific men living in South Auckland with a history of boxing presenting with early onset dementia. We discuss the history of boxing in Pacific people and the possibility of increased risk of early onset dementia in New Zealand Pacific men compared to their European counterparts. We reviewed the files of Pacific men with a history of amateur or professional boxing who presented to our memory and older adult mental health services with early onset dementia over a 45-month period. We gathered relevant information to construct a biopsychosocial paradigm as possible explanation of this phenomenon. We identified a series of eight New Zealand Pacific men with early onset dementia and with a history of boxing. Alcohol was a contributing factor in seven of the eight cases, and vascular risk factors in five. Historical, cultural and socio-economic factors underpin the attraction of some Pacific men to boxing as a sport. Given that New Zealand Pacific peoples may have an earlier onset of dementia than their European counterparts, further research is required to establish whether boxing is a contributory factor. Sports physicians should advise young New Zealand Pacific boxers about the long-term risks associated with their sport.

Relevance of the hygiene hypothesis to early vs. late onset allergic rhinitis.

PubMed

Matheson, M C; Walters, E H; Simpson, J A; Wharton, C L; Ponsonby, A-L; Johns, D P; Jenkins, M A; Giles, G G; Hopper, J L; Abramson, M J; Dharmage, S C

2009-03-01

The hygiene hypothesis proposes that reduced exposure to infections in early life increases the risk of developing allergic conditions including allergic rhinitis. We examined the association between markers of the hygiene hypothesis and allergic rhinitis that developed before 7 years of age and allergic rhinitis that developed after 7 years of age. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort (n=8583) study of respiratory disease. Participants have been followed from 7 to 44 years of age. Information on potential risk factors, allergies and respiratory symptoms was collected longitudinally. Using multi-nomial logistic regression, exposure to siblings, infections, tonsillectomy and farm residence during childhood were examined as risk factors for allergic rhinitis that developed before or after 7 years of age. All analyses were adjusted for gender, maternal and paternal atopy, mother's age at participant's birth, paternal socio-economic status in 1968 and personal socio-economic status in 2004. Greater cumulative exposure to siblings before the age of 2 years was strongly inversely associated with early onset allergic rhinitis (<1 year sib exposure: OR=0.6, 95% CI 0.3-1.0; 1-3 years sib exposure: OR=0.6, 95% CI 0.4-0.9; >3 years sib exposure: OR=0.4, 95% CI 0.3-0.8) less so with later onset allergic rhinitis. The risk of early onset allergic rhinitis decreased with increasing viral infections (OR=0.7, 95% CI 0.5-0.9) during childhood. Having a tonsillectomy before 7 years of age increased the risk of early onset allergic rhinitis (OR=1.7, 95% CI 1.2-2.5). None of these factors was associated with later onset allergic rhinitis. Exposures relevant to the hygiene hypothesis were important predictors for the development of early onset but less so for later onset allergic rhinitis. The exact mechanisms by which siblings and infections protect against allergic rhinitis are unclear. The stronger findings for earlier onset allergic rhinitis

Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

PubMed

Hartz, Sarah M; Short, Susan E; Saccone, Nancy L; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Gubjartsson, Daniel; Hansel, Nadia N; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo-Pekka; Michel, Martha; Rawal, Rajesh; Rosenberger, Albert; Scheet, Paul; Shaffer, John R; Teumer, Alexander; Thompson, John R; Vink, Jacqueline M; Vogelzangs, Nicole; Wenzlaff, Angela S; Wheeler, William; Xiao, Xiangjun; Yang, Bao-Zhu; Aggen, Steven H; Balmforth, Anthony J; Baumeister, Sebastian E; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W; Boyd, Heather A; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu-Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M; Hayward, Caroline; Heikkilä, Kauko; Hewitt, John K; Hottenga, Jouke Jan; Jensen, Majken K; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J; Konte, Bettina; Korhonen, Tellervo; Landi, Maria-Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M; Mathias, Rasika A; McNeil, Daniel W; Medland, Sarah E; Montgomery, Grant W; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J; Francks, Clyde; Gejman, Pablo V; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S; Lehtimäki, Terho; Levinson, Douglas F; Marazita, Mary L; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D; Murray, Jeffrey C; Nöthen, Markus M; Penninx, Brenda W; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J; Sanders, Alan R; Schwartz, Ann G; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H-Erich; Amos, Christopher I; Breslau, Naomi; Cannon, Dale S; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G; Stevens, Victoria L; Stitzel, Jerry A; Weiss, Robert B; Kraft, Peter; Bierut, Laura J

2012-08-01

Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

Operational Thought in Alzheimer's Disease Early Onset and SDAT.

ERIC Educational Resources Information Center

Emery, Olga B.; Breslau, Lawrence D.

For more than a decade it has been convention to assume that senile dementia Alzheimer's type (SDAT) and Alzheimer's disease early onset represent a unitary disease process with only an onset difference. This assumption has been neither confirmed nor disconfirmed. To address this issue, a study was conducted which analyzed the dissolution of…

The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians.

PubMed

Yang, M Y; Kim, J M; Kim, G W; Mun, J H; Song, M; Ko, H C; Kim, B S; Kim, H S; Kim, M B

2017-01-01

Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group. © 2016 European Academy of Dermatology and Venereology.

Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer

PubMed Central

Pearlman, Rachel; Frankel, Wendy L.; Swanson, Benjamin; Zhao, Weiqiang; Yilmaz, Ahmet; Miller, Kristin; Bacher, Jason; Bigley, Christopher; Nelsen, Lori; Goodfellow, Paul J.; Goldberg, Richard M.; Paskett, Electra; Shields, Peter G.; Freudenheim, Jo L.; Stanich, Peter P; Lattimer, Ilene; Arnold, Mark; Liyanarachchi, Sandya; Kalady, Matthew; Heald, Brandie; Greenwood, Carla; Paquette, Ian; Prues, Marla; Draper, David J.; Lindeman, Carolyn; Kuebler, J. Philip; Reynolds, Kelly; Brell, Joanna M.; Shaper, Amy A.; Mahesh, Sameer; Buie, Nicole; Weeman, Kisa; Shine, Kristin; Haut, Mitchell; Edwards, Joan; Bastola, Shyamal; Wickham, Karen; Khanduja, Karamjit S.; Zacks, Rosemary; Pritchard, Colin C.; Shirts, Brian H.; Jacobson, Angela; Allen, Brian; de la Chapelle, Albert; Hampel, Heather

2017-01-01

IMPORTANCE Hereditary cancer syndromes infer high cancer risks and require intensive cancer surveillance, yet the prevalence and spectrum of these conditions among unselected patients with early-onset colorectal cancer (CRC) is largely undetermined. OBJECTIVE To determine the frequency and spectrum of cancer susceptibility gene mutations among patients with early-onset CRC. DESIGN, SETTING, AND PARTICIPANTS Overall, 450 patients diagnosed with colorectal cancer younger than 50 years were prospectively accrued from 51 hospitals into the Ohio Colorectal Cancer Prevention Initiative from January 1, 2013, to June 20, 2016. Mismatch repair (MMR) deficiency was determined by microsatellite instability and/or immunohistochemistry. Germline DNA was tested for mutations in 25 cancer susceptibility genes using next-generation sequencing. MAIN OUTCOMES AND MEASURES Mutation prevalence and spectrum in patients with early-onset CRC was determined. Clinical characteristics were assessed by mutation status. RESULTS In total 450 patients younger than 50 years were included in the study, and 75 gene mutations were found in 72 patients (16%). Forty-eight patients (10.7%) had MMR-deficient tumors, and 40 patients (83.3%) had at least 1 gene mutation: 37 had Lynch syndrome (13, MLH1 [including one with constitutional MLH1 methylation]; 16, MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 patient had the APC c.3920T>A, p.I1307K mutation and a PMS2 variant; 9 patients (18.8%) had double somatic MMR mutations (including 2 with germline biallelic MUTYH mutations); and 1 patient had somatic MLH1 methylation. Four hundred two patients (89.3%) had MMR-proficient tumors, and 32 patients (8%) had at least 1 gene mutation: 9 had mutations in high-penetrance CRC genes (5, APC; 1, APC/PMS2; 2, biallelic MUTYH; 1, SMAD4); 13 patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC (3, ATM; 1, ATM/CHEK2; 2, BRCA1; 4, BRCA2; 1, CDKN2A; 2, PALB2); 10

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

PubMed

Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

2015-09-01

Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association of Sepsis-Related Mortality with Early Increase of TIMP-1/MMP-9 Ratio

PubMed Central

Lorente, Leonardo; Martín, María M.; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan M.; Orbe, Josune; Rodríguez, José A.; Jiménez, Alejandro; Páramo, José A.

2014-01-01

Objective Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Methods Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. Results We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. Conclusions The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis

Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio.

PubMed

Lorente, Leonardo; Martín, María M; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan M; Orbe, Josune; Rodríguez, José A; Jiménez, Alejandro; Páramo, José A

2014-01-01

Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome.

Early outcome of early-goal directed therapy for patients with sepsis or septic shock: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Chen, Xiaofan; Zhu, Weifeng; Tan, Jing; Nie, Heyun; Liu, Liangming; Yan, Dongmei; Zhou, Xu; Sun, Xin

2017-04-18

Various trials and meta-analyses have reported conflicting results concerning the application of early goal-directed therapy (EGDT) for sepsis and septic shock. The aim of this study was to update the evidence by performing a systematic review and meta-analysis. Multiple databases were searched from initial through August, 2016 for randomized controlled trials (RCTs) which investigated the associations between the use of EGDT and mortality in patients with sepsis or septic shock. Meta-analysis was performed using random-effects model and heterogeneity was examined through subgroup analyses. The primary outcome of interest was patient all-cause mortality including hospital or ICU mortality. Seventeen RCTs including 6207 participants with 3234 in the EGDT group and 2973 in the control group were eligible for this study. Meta-analysis showed that EGDT did not significantly reduce hospital or intensive care unit (ICU) mortality (relative risk [RR] 0.89, 95% CI 0.78 to 1.02) compared with control group for patients with sepsis or septic shock. The findings of subgroup analyses stratified by study region, number of research center, year of enrollment, clinical setting, sample size, timing of EGDT almost remained constant with that of the primary analysis. Our findings provide evidence that EGDT offers neutral survival effects for patients with sepsis or septic shock. Further meta-analyses based on larger well-designed RCTs or individual patient data meta-analysis are required to explore the survival benefits of EDGT in patients with sepsis or septic shock.

Modified obstetric early warning scoring systems (MOEWS): validating the diagnostic performance for severe sepsis in women with chorioamnionitis.

PubMed

Edwards, Sian E; Grobman, William A; Lappen, Justin R; Winter, Cathy; Fox, Robert; Lenguerrand, Erik; Draycott, Timothy

2015-04-01

We sought to compare the predictive power of published modified obstetric early warning scoring systems (MOEWS) for the development of severe sepsis in women with chorioamnionitis. This was a retrospective cohort study using prospectively collected clinical observations at a single tertiary unit (Chicago, IL). Hospital databases and patient records were searched to identify and verify cases with clinically diagnosed chorioamnionitis during the study period (June 2006 through November 2007). Vital sign data (heart rate, respiratory rate, blood pressure, temperature, mental state) for these cases were extracted from an electronic database and the single worst composite recording was identified for analysis. Global literature databases were searched (2014) to identify examples of MOEWS. Scores for each identified MOEWS were derived from each set of vital sign recordings during the presentation with chorioamnionitis. The performance of these MOEWS (the primary outcome) was then analyzed and compared using their sensitivity, specificity, positive and negative predictive values, and receiver-operating characteristic curve for severe sepsis. Six MOEWS were identified. There was wide variation in design and pathophysiological thresholds used for clinical alerts. In all, 913 women with chorioamnionitis were identified from the clinical database. In all, 364 cases with complete data for all physiological indicators were included in analysis. Five women developed severe sepsis, including 1 woman who died. The sensitivities of the MOEWS in predicting the severe deterioration ranged from 40-100% and the specificities varied even more ranging from 4-97%. The positive predictive values were low for all MOEWS ranging from <2-15%. The MOEWS with simpler designs tended to be more sensitive, whereas the more complex MOEWS were more specific, but failed to identify some of the women who developed severe sepsis. Currently used MOEWS vary widely in terms of alert thresholds, format

Out-of-Hospital Fluid in Severe Sepsis: Effect on Early Resuscitation in the Emergency Department

PubMed Central

Seymour, Christopher W.; Cooke, Colin R.; Mikkelsen, Mark E.; Hylton, Julie; Rea, Tom D.; Goss, Christopher H.; Gaieski, David F.; Band, Roger A.

2014-01-01

Background Early identification and treatment of patients with severe sepsis improves outcome, yet the role of out-of-hospital intravenous (IV) fluid is unknown. Objective To determine if the delivery of out-of-hospital fluid in patients with severe sepsis is associated with reduced time to achievement of goal-oriented resuscitation in the emergency department (ED). Methods We performed a secondary data analysis of a retrospective cohort study in a metropolitan, tertiary care, university-based medical center supported by a two-tiered system of out-of-hospital emergency medical services (EMS) providers. We studied the association between delivery of out-of-hospital fluid by advanced life support (ALS) providers and the achievement of resuscitation endpoints (central venous pressure [CVP] ≥8 mmHg, mean arterial pressure [MAP] ≥65 mmHg, and central venous oxygen saturation [ScvO2] ≥70%) within six hours after triage during early goal-directed therapy (EGDT) in the ED. Results Twenty five (48%) of 52 patients transported by ALS with severe sepsis received out-of-hospital fluid. Data for age, gender, source of sepsis, and presence of comorbidities were similar between patients who did and did not receive out-of-hospital fluid. Patients receiving out-of-hospital fluid had lower out-of-hospital mean (± standard deviation) systolic blood pressure (95 ± 40 mmHg vs. 117 ± 29 mmHg; p = 0.03) and higher median (interquartile range) Sequential Organ Failure Assessment (SOFA) scores in the ED (7 [5–8] vs. 4 [4–6]; p = 0.01) than patients not receiving out-of-hospital fluid. Despite greater severity of illness, patients receiving out-of-hospital fluid approached but did not attain a statistically significant increase in the likelihood of achieving MAP ≥65 mmHg within six hours after ED triage (70% vs. 44%, p = 0.09). On average, patients receiving out-of-hospital fluid received twice the fluid volume within one hour after ED triage (1.1 L [1.0–2.0 L] vs. 0.6 L [0

Immunotherapy in the management of sepsis.

PubMed Central

Fagan, E. A.; Singer, M.

1995-01-01

The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. Later deaths are related more closely to the consequences of multiple organ dysfunction. Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support. PMID:7724438

Using Heuristic Evaluation to Improve Sepsis Alert Usability.

PubMed

Pertiwi, Ariani Arista Putri; Fraczkowski, Dan; Stogis, Sheryl L; Lopez, Karen Dunn

2018-06-01

Sepsis, life-threatening organ dysfunction in response to infection, is an alarmingly common and aggressive illness in US hospitals, especially for intensive care patients. Preventing sepsis deaths rests on the clinicians' ability to promptly recognize and treat sepsis. To aid early recognition, many organizations have employed clinician-facing electronic sepsis alert systems. However, the effectiveness of the alert relies on heavily on the visual interface, textual information, and overall usability. This article reports a usability inspection of a sepsis alert system. The authors found violations in 12 of the 14 usability principles and promote use of this method in practice to systematically identify usability problems. Copyright © 2018 Elsevier Inc. All rights reserved.

Childhood Risk Factors for Early-Onset Drinking*

PubMed Central

Donovan, John E.; Molina, Brooke S. G.

2011-01-01

Objective: There is relatively little research on the childhood antecedent predictors of early-onset alcohol use. This study examined an array of psychosocial variables assessed at age 10 and reflecting Problem Behavior Theory as potential antecedent risk factors for the initiation of alcohol use at age 14 or younger. Method: A sample of 452 children (238 girls) ages 8 or 10 and their families was drawn from Allegheny County, PA, using targeted-age directory sampling and random-digit dialing procedures. Children and parents were interviewed using computer-assisted interviews. Logistic regression analyses were used to examine the age-10 univariate and multivariate predictors of the initiation of alcohol use by age 14 or younger. Results: Twenty-five percent of the sample reported having more than a sip or a taste of alcohol in their life by age 14. Sex, race, and age cohort did not relate to early drinking status. Children with two parents were less likely to initiate drinking early. Early initiation of drinking related significantly to an array of antecedent risk factors (personality, social environment, and behavioral) assessed at age 10 that reflect psychosocial proneness for problem behavior. In the multivariate model, the variables most predictive of early-onset drinking were having a single parent, sipping or tasting alcohol by age 10, having parents who also started drinking at an early age, and parental drinking frequency. Conclusions: Initiation of alcohol use by age 14 reflects childhood psychosocial proneness to engage in problem behavior as measured by Problem Behavior Theory and having a family environment conducive to alcohol use. PMID:21906502

Early Onset Malignancies - Genomic Study of Cancer Disparities

Cancer.gov

The Early Onset Malignancies Initiative studies the genomic basis of six cancers that develop at an earlier age, occur in higher rates, and are typically more aggressive in certain minority populations.

Early onset type 2 diabetes: risk factors, clinical impact and management

PubMed Central

Idris, Iskandar

2014-01-01

Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a significant impact on the individual, healthcare service delivery and planning. The individuals are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black and minority ethnic (BME) origin and come from a less affluent socioeconomic group. They have a heightened risk of developing microvascular and macrovascular complications, often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such, early and aggressive risk factor management is warranted. Early onset T2DM is complex and impacts on service delivery with a need for multidisciplinary care of complications and comorbidities’, in addition to adequate educational and psychological support. This review on the impact of early onset T2DM provides the latest insights into this emerging epidemic. PMID:25364491

Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery.

PubMed

Mokart, D; Merlin, M; Sannini, A; Brun, J P; Delpero, J R; Houvenaeghel, G; Moutardier, V; Blache, J L

2005-06-01

Patients who undergo major surgery for cancer are at high risk of postoperative sepsis. Early markers of septic complications would be useful for diagnosis and therapeutic management in patients with postoperative sepsis. The aim of this study was to investigate the association between early (first postoperative day) changes in interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) serum concentrations and the occurrence of subsequent septic complications after major surgery. Serial blood samples were collected from 50 consecutive patients for determination of IL-6, PCT and CRP serum levels. Blood samples were obtained on the morning of surgery and on the morning of the first postoperative day. Sixteen patients developed septic complications during the first five postoperative days (group 1), and 34 patients developed no septic complications (group 2). On day 1, PCT and IL-6 levels were significantly higher in group 1 (P-values of 0.003 and 0.006, respectively) but CRP levels were similar. An IL-6 cut-off point set at 310 pg ml(-1) yielded a sensitivity of 90% and a specificity of 58% to differentiate group 1 patients from group 2 patients. When associated with the occurrence of SIRS on day 1 these values reached 100% and 79%, respectively. A PCT cut-off point set at 1.1 ng ml(-1) yielded a sensitivity of 81% and a specificity of 72%. When associated with the occurrence of SIRS on day 1, these values reached 100% and 86%, respectively. PCT and IL-6 appear to be early markers of subsequent postoperative sepsis in patients undergoing major surgery for cancer. These findings could allow identification of postoperative septic complications.

Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India

PubMed Central

Raman, Ratheesh; Kotapalli, Viswakalyan; Adduri, Raju; Gowrishankar, Swarnalata; Bashyam, Leena; Chaudhary, Ajay; Vamsy, Mohana; Patnaik, Sujith; Srinivasulu, Mukta; Sastry, Regulagadda; Rao, Subramanyeshwar; Vasala, Anjayneyulu; Kalidindi, NarasimhaRaju; Pollack, Jonathan; Murthy, Sudha; Bashyam, Murali

2012-01-01

Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for greater than 90% of late-onset colorectal cancer. Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India. PMID:23168910

Inadequate exercise as a risk factor for sepsis mortality.

PubMed

Williams, Paul T

2013-01-01

Test whether inadequate exercise is related to sepsis mortality. Mortality surveillance of an epidemiological cohort of 155,484 National Walkers' and Runners' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded. Sepsis was the underlying cause in 54 deaths (sepsis(underlying)) and a contributing cause in 184 deaths (sepsis(contributing)), or 238 total sepsis-related deaths (sepsis(total)). Inadequate exercise was associated with 2.24-fold increased risk for sepsis(underlying) (95%CI: 1.21 to 4.07-fold, P = 0.01), 2.11-fold increased risk for sepsis(contributing) (95%CI: 1.51- to 2.92-fold, P<10(-4)), and 2.13-fold increased risk for sepsis(total) (95%CI: 1.59- to 2.84-fold, P<10(-6)) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsis(total) risk was greater in diabetics (P = 10(-5)), cancer survivors (P = 0.0001), and heart attack survivors (P = 0.003) and increased with waist circumference (P = 0.0004). The sepsis(total) risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsis(total) risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P = 0.0001) when adjusted, which was significantly greater (P = 0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P = 0

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

ERIC Educational Resources Information Center

McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

2007-01-01

Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin.

PubMed

Gao, Liqin; Yang, Bin; Zhang, Hairong; Ou, Qishui; Lin, Yulan; Zhang, Mei; Zhang, Zhenhuan; Kim, Sunghee; Wu, Bing; Wang, Zeng; Fu, Lengxi; Lin, Jingan; Chen, Ruiqing; Lan, Ruilong; Chen, Junying; Chen, Wei; Chen, Long; Zhang, Hengshan; Han, Deping; Chen, Jingrong; Okunieff, Paul; Lin, Jianhua; Zhang, Lurong

2018-02-16

Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis ( n = 134), SIRS ( n = 60) and normal adults ( n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1-2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis ( r s = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1-2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.

Key process indicators of mortality in the implementation of protocol-driven therapy for severe sepsis.

PubMed

Wang, Jiun-Long; Chin, Chun-Shih; Chang, Ming-Chen; Yi, Chi-Yuan; Shih, Sou-Jen; Hsu, Jeng-Yuan; Wu, Chieh-Liang

2009-10-01

Severe sepsis and septic shock are life-threatening disorders. Integrating treatments into a bundle strategy has been proposed to facilitate timely resuscitation, but is difficult to implement. We implemented protocol-driven therapy for severe sepsis, and analyzed retrospectively the key process indicators of mortality in managing sepsis. Continuous quality improvement was begun to implement a tailored protocol-driven therapy for sepsis in a 24-bed respiratory intensive care unit (RICU) of Taichung Veterans General Hospital from January 2007 to February 2008. Patients, who were admitted to the RICU directly, or within 24 hours, were enrolled if they met the criteria for severe sepsis and septic shock. Disease severity [Acute Physiology and Chronic Health Evaluation (APACHE) II and lactate level], causes of sepsis, comorbidity and site of sepsis onset were recorded. Process-of-care indicators included resuscitation time (Tr-s), RICU bed availability (Ti-s) and the ratio of completing the elements of the protocol at 1, 2, 4 and 6 hours. The structure and process-of-care indicators reflated to mortality at 7 days after RICU admission and at RICU discharge were identified retrospectively. Eighty-six patients (mean age, 71 +/- 14 years, 72 men, 14 women, APACHE II, 25.0 +/- 7.0) were enrolled. APACHE II scores and lactate levels were higher for mortality than survival at 7 days after RICU admission (p < 0.01). For the process-of-care indicators, Ti-s (562.2 +/- 483.3 vs.1017.3 +/- 557.8 minutes, p = 0.03) and Tr-s (60.7 +/- 207.8 vs. 248.5 +/- 453.1 minutes, p = 0.07) were shorter for survival than mortality at 7 days after RICU admission. The logistic regression study showed that Tr-s was an important indicator. The ratio of completing the elements of protocols at 1, 2, 4 and 6 hours ranged from 70% to 90% and was not related to mortality. Protocol-driven therapy for sepsis was put into clinical practice. Early resuscitation and ICU bed availability were key process

Triage sepsis alert and sepsis protocol lower times to fluids and antibiotics in the ED.

PubMed

Hayden, Geoffrey E; Tuuri, Rachel E; Scott, Rachel; Losek, Joseph D; Blackshaw, Aaron M; Schoenling, Andrew J; Nietert, Paul J; Hall, Greg A

2016-01-01

Early identification of sepsis in the emergency department (ED), followed by adequate fluid hydration and appropriate antibiotics, improves patient outcomes. We sought to measure the impact of a sepsis workup and treatment protocol (SWAT) that included an electronic health record (EHR)-based triage sepsis alert, direct communication, mobilization of resources, and standardized order sets. We conducted a retrospective, quasiexperimental study of adult ED patients admitted with suspected sepsis, severe sepsis, or septic shock. We defined a preimplementation (pre-SWAT) group and a postimplementation (post-SWAT) group and further broke these down into SWAT A (septic shock) and SWAT B (sepsis with normal systolic blood pressure). We performed extensive data comparisons in the pre-SWAT and post-SWAT groups, including demographics, systemic inflammatory response syndrome criteria, time to intravenous fluids bolus, time to antibiotics, length-of-stay times, and mortality rates. There were 108 patients in the pre-SWAT group and 130 patients in the post-SWAT group. The mean time to bolus was 31 minutes less in the postimplementation group, 51 vs 82 minutes (95% confidence interval, 15-46; P value < .01). The mean time to antibiotics was 59 minutes less in the postimplementation group, 81 vs 139 minutes (95% confidence interval, 44-74; P value < .01). Segmented regression modeling did not identify secular trends in these outcomes. There was no significant difference in mortality rates. An EHR-based triage sepsis alert and SWAT protocol led to a significant reduction in the time to intravenous fluids and time to antibiotics in ED patients admitted with suspected sepsis, severe sepsis, and septic shock. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of community-onset Staphylococcus argenteus and Staphylococcus aureus sepsis in Thailand: a prospective multicentre observational study.

PubMed

Chantratita, N; Wikraiphat, C; Tandhavanant, S; Wongsuvan, G; Ariyaprasert, P; Suntornsut, P; Thaipadungpanit, J; Teerawattanasook, N; Jutrakul, Y; Srisurat, N; Chaimanee, P; Anukunananchai, J; Phiphitaporn, S; Srisamang, P; Chetchotisakd, P; West, T E; Peacock, S J

2016-05-01

Staphylococcus argenteus is a globally distributed cause of human infection, but diagnostic laboratories misidentify this as Staphylococcus aureus. We determined whether there is clinical utility in distinguishing between the two. A prospective cohort study of community-onset invasive staphylococcal sepsis was conducted in adults at four hospitals in northeast Thailand between 2010 and 2013. Of 311 patients analysed, 58 (19%) were infected with S. argenteus and 253 (81%) with S. aureus. Most S. argenteus (54/58) were multilocus sequence type 2250. Infection with S. argenteus was more common in males, but rates of bacteraemia and drainage procedures were similar in the two groups. S. argenteus precipitated significantly less respiratory failure than S. aureus (5.2% versus 20.2%, adjusted OR 0.21, 95% CI 0.06-0.74, p 0.015), with a similar but non-significant trend for shock (6.9% versus 12.3%, adjusted OR 0.46, 95% CI 0.15-1.44, p 0.18). This did not translate into a difference in death at 28 days (6.9% versus 8.7%, adjusted OR 0.80, 95% CI 0.24-2.65, p 0.72). S. argenteus was more susceptible to antimicrobial drugs compared with S. aureus, and contained fewer toxin genes although pvl was detected in 16% (9/58). We conclude that clinical differences exist in association with sepsis due to S. argenteus versus S. aureus. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Polarization of microglia and its role in bacterial sepsis.

PubMed

Michels, Monique; Sonai, Beatriz; Dal-Pizzol, Felipe

2017-02-15

Microglial polarization in response to brain inflammatory conditions is a crescent field in neuroscience. However, the effect of systemic inflammation, and specifically sepsis, is a relatively unexplored field that has great interest and relevance. Sepsis has been associated with both early and late harmful events of the central nervous system, suggesting that there is a close link between sepsis and neuroinflammation. During sepsis evolution it is supposed that microglial could exert both neurotoxic and repairing effects depending on the specific microglial phenotype assumed. In this context, here it was reviewed the role of microglial polarization during sepsis-associated brain dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Common variants at five new loci associated with early-onset inflammatory bowel disease.

PubMed

Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

2009-12-01

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients

PubMed Central

Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2017-01-01

Introduction Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Methods Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. Ethics and dissemination This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. PMID:28765125

Functional outcomes in pediatric severe sepsis: further analysis of the researching severe sepsis and organ dysfunction in children: a global perspective trial.

PubMed

Farris, Reid W D; Weiss, Noel S; Zimmerman, Jerry J

2013-11-01

individual's clinical course are associated with poor functional outcome 28 days after onset of severe sepsis. These characteristics may provide opportunity for intervention in order to improve functional outcome in pediatric patients with severe sepsis. Decline in functional status 28 days after onset of severe sepsis is a frequent and potentially clinically meaningful event. Utilization of functional status as the primary outcome in future pediatric sepsis clinical trials should be considered.

Acute Neonatal Parotitis with Late-Onset Septic Shock due to Streptococcus agalactiae

PubMed Central

Boulyana, M.

2014-01-01

Acute neonatal parotitis (ANP) is a very rare disease. Most cases are managed conservatively; early antibiotics and adequate hydration may reduce the need for surgery. The most common cause of ANP is Staphylococcus aureus. We report a rare case of acute neonatal parotitis with late-onset septic shock due to Streptococcus agalactiae. The diagnosis was confirmed with ultrasound and isolation of Streptococcus agalactiae from blood culture. The patient was treated successfully with 10 days of intravenous antibiotics and supportive measures. Despite being rare, streptococcal ANP should be considered in the etiological diagnosis of neonatal sepsis. Early diagnosis and appropriate antibiotic might prevent serious complications. PMID:24653847

Risk of early-onset prostate cancer associated with occupation in the Nordic countries.

PubMed

Barry, Kathryn Hughes; Martinsen, Jan Ivar; Alavanja, Michael C R; Andreotti, Gabriella; Blair, Aaron; Hansen, Johnni; Kjærheim, Kristina; Koutros, Stella; Lynge, Elsebeth; Sparèn, Pär; Tryggvadottir, Laufey; Weiderpass, Elisabete; Berndt, Sonja I; Pukkala, Eero

2017-12-01

Early-onset prostate cancer is often more aggressive and may have a different aetiology than later-onset prostate cancer, but has been relatively little studied to date. We evaluated occupation in relation to early- and later-onset prostate cancer in a large pooled study. We used occupational information from census data in five Nordic countries from 1960 to 1990. We identified prostate cancer cases diagnosed from 1961 to 2005 by linkage of census information to national cancer registries and calculated standardised incidence ratios (SIRs) separately for men aged 30-49 and those aged 50 or older. We also conducted separate analyses by period of follow-up, 1961-1985 and 1986-2005, corresponding to pre- and post-prostate-specific antigen (PSA) screening. For early-onset prostate cancer (n = 1521), we observed the highest SIRs for public safety workers (e.g. firefighters) (SIR = 1.71, 95% confidence interval [CI]: 1.23-2.31) and military personnel (SIR = 1.97, 95% CI: 1.31-2.85). These SIRs were significantly higher than the SIRs for later-onset disease (for public safety workers, SIR = 1.10, 95% CI: 1.07-1.14 and for military personnel, SIR = 1.09, 95% CI: 1.05-1.13; p heterogeneity  = 0.005 and 0.002, respectively). Administrators and technical workers also demonstrated significantly increased risks for early-onset prostate cancer, but the SIRs did not differ from those of later-onset disease (p heterogeneity >0.05). While our early-onset finding for public safety workers was restricted to the post-PSA period, that for military personnel was restricted to the pre-PSA period. Our results suggest that occupational exposures, particularly for military personnel, may be associated with early-onset prostate cancer. Further evaluation is needed to explain these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Framework for evaluating public health surveillance systems for early detection of outbreaks: recommendations from the CDC Working Group.

PubMed

Buehler, James W; Hopkins, Richard S; Overhage, J Marc; Sosin, Daniel M; Tong, Van

2004-05-07

The threat of terrorism and high-profile disease outbreaks has drawn attention to public health surveillance systems for early detection of outbreaks. State and local health departments are enhancing existing surveillance systems and developing new systems to better detect outbreaks through public health surveillance. However, information is limited about the usefulness of surveillance systems for outbreak detection or the best ways to support this function. This report supplements previous guidelines for evaluating public health surveillance systems. Use of this framework is intended to improve decision-making regarding the implementation of surveillance for outbreak detection. Use of a standardized evaluation methodology, including description of system design and operation, also will enhance the exchange of information regarding methods to improve early detection of outbreaks. The framework directs particular attention to the measurement of timeliness and validity for outbreak detection. The evaluation framework is designed to support assessment and description of all surveillance approaches to early detection, whether through traditional disease reporting, specialized analytic routines for aberration detection, or surveillance using early indicators of disease outbreaks, such as syndromic surveillance.

Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

ERIC Educational Resources Information Center

Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

2010-01-01

Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

ERIC Educational Resources Information Center

Danner, Stephanie; Fristad, Mary A.; Arnold, L. Eugene; Youngstrom, Eric A.; Birmaher, Boris; Horwitz, Sarah M.; Demeter, Christine; Findling, Robert L.; Kowatch, Robert A.

2009-01-01

Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current…

Early Onset Marijuana Use Is Associated with Learning Inefficiencies

PubMed Central

Schuster, Randi Melissa; Hoeppner, Susanne S.; Evins, A. Eden; Gilman, Jodi M.

2016-01-01

Objective Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early-onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Method Forty-eight young adults, aged 18–25, who used marijuana at least once per week and 48 matched non-using controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: ‘early onset’ users (EMJ), who started using marijuana at or before age 16 (n = 27), and ‘late onset’ marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Results Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Conclusions Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. PMID:26986749

Biomarkers predicting sepsis in polytrauma patients: Current evidence.

PubMed

Ciriello, Vincenzo; Gudipati, Suribabu; Stavrou, Petros Z; Kanakaris, Nikolaos K; Bellamy, Mark C; Giannoudis, Peter V

2013-12-01

Major trauma still represents one of the leading causes of death in the first four decades of life. Septic complications represent the predominant causes of late death (45% of overall mortality) in polytrauma patients. The ability of clinicians to early differentiate between systemic inflammatory response syndrome (SIRS) and sepsis is demonstrated to improve clinical outcome and mortality. The identification of an "ideal" biomarker able to early recognize incoming septic complications in trauma patients is still a challenge for researchers. To evaluate the existing evidence regarding the role of biomarkers to predict or facilitate early diagnosis of sepsis in trauma patients, trying to compile some recommendations for the clinical setting. An Internet-based search of the MEDLINE, EMBASE and Cochrane Library databases was performed using the search terms: "Biomarkers", "Sepsis" and "Trauma" in various combinations. The methodological quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies Checklist (QUADAS). After data extraction, the level of evidence available for each bio-marker was rated and presented using the "best-evidence synthesis" method, in line with the US Agency for Healthcare Research and Quality. Thirty studies were eligible for the final analysis: 13 case-control studies and 17 cohort studies. The "strong evidence" available demonstrated the potential use of procalcitonin as an early indicator of post-traumatic septic complications and reported the inability of c-reactive protein (CRP) to specifically identify infective complications. Moderate, conflicting and limited evidence are available for the other 31 biomarkers. Several biomarkers have been evaluated for predicting or making early diagnosis of sepsis in trauma patients. Current evidence does not support the use of a single biomarker in diagnosing sepsis. However, procalcitonin trend was found to be useful in early identification of post

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

PubMed

Szakmany, T; Pugh, R; Kopczynska, M; Lundin, R M; Sharif, B; Morgan, P; Ellis, G; Abreu, J; Kulikouskaya, S; Bashir, K; Galloway, L; Al-Hassan, H; Grother, T; McNulty, P; Seal, S T; Cains, A; Vreugdenhil, M; Abdimalik, M; Dennehey, N; Evans, G; Whitaker, J; Beasant, E; Hall, C; Lazarou, M; Vanderpump, C V; Harding, K; Duffy, L; Guerrier Sadler, A; Keeling, R; Banks, C; Ng, S W Y; Heng, S Y; Thomas, D; Puw, E W; Otahal, I; Battle, C; Minik, O; Lyons, R A; Hall, J E

2018-02-01

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Biomarkers for diagnosis of neonatal sepsis: a literature review.

PubMed

Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

2018-06-01

Sepsis is an important cause of mortality and morbidity in neonatal populations. There has been constant search of an ideal sepsis biomarker that have high sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), so that both the diagnosis and exclusion of neonatal sepsis can be made at the earliest possible and appropriate antibiotics can be started to neonate. Ideal sepsis biomarker will help in guiding us when not to start antibiotics in case of suspect sepsis and total duration of antibiotics course in case of proven sepsis. There are numerous sepsis biomarkers that have been evaluated for early detection of neonatal sepsis but till date there is no single ideal biomarker that fulfills all essential criteria's for being an ideal biomarker. The most commonly used biomarkers are C-reactive protein (CRP) and procalcitonin (PCT), but both have shown varied sensitivity, specificity, PPV and NPV in different studies. We conducted literature search for various neonatal sepsis biomarkers and this review article will cover briefly all the markers with current available evidence.

Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

PubMed Central

Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

2015-01-01

Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

Epidermal growth factor treatment decreases mortality and is associated with improved gut integrity in sepsis.

PubMed

Clark, Jessica A; Clark, Andrew T; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2008-07-01

Epidermal growth factor (EGF) is a cytoprotective peptide that has healing effects on the intestinal mucosa. We sought to determine whether systemic administration of EGF after the onset of sepsis improved intestinal integrity and decreased mortality. FVB/N mice were subjected to either sham laparotomy or 2 x 23 cecal ligation and puncture (CLP). Septic mice were further randomized to receive injection of either 150 microg kg(-1) d(-1) (i.p.) EGF or 0.9% saline (i.p.). Circulating EGF levels were decreased after CLP compared with sham animals but were unaffected by giving exogenous EGF treatment. In contrast, intestinal EGF levels increased after CLP and were further augmented by exogenous EGF treatment. Intestinal EGF receptor was increased after CLP, whether assayed by immunohistochemistry, real-time polymerase chain reaction, or Western blot, and exogenous EGF treatment decreased intestinal EGF receptor. Villus length decreased 2-fold between sham and septic animals, and EGF treatment resulted in near total restitution of villus length. Sepsis decreased intestinal proliferation and increased intestinal apoptosis. This was accompanied by increased expression of the proapoptotic proteins Bid and Fas-associated death domain, as well as the cyclin-dependent kinase inhibitor p21 cip1/waf Epidermal growth factor treatment after the onset of sepsis restored both proliferation and apoptosis to levels seen in sham animals and normalized expression of Bid, Fas-associated death domain, and p21 cip1/waf . To determine whether improvements in gut homeostasis were associated with a decrease in sepsis-induced mortality, septic mice with or without EGF treatment after CLP were followed 7 days for survival. Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (P < 0.05). Thus, EGF may be a potential therapeutic agent for the treatment of sepsis in part due to its ability to protect intestinal integrity.

Epidermal growth factor treatment decreases mortality and is associated with improved gut integrity in sepsis

PubMed Central

Clark, Jessica A.; Clark, Andrew T.; Hotchkiss, Richard S.; Buchman, Timothy G.; Coopersmith, Craig M.

2007-01-01

Epidermal growth factor (EGF) is a cytoprotective peptide that has healing effects on the intestinal mucosa. We sought to determine whether systemic administration of EGF following the onset of sepsis improved intestinal integrity and decreased mortality. FVB/N mice were subjected to either sham laparotomy or 2×23 cecal ligation and puncture (CLP). Septic mice were further randomized to receive intraperitoneal injection of either 150 μg/kg/day EGF or 0.9% saline. Circulating EGF levels were decreased following CLP compared to sham animals but were unaffected by giving exogenous EGF treatment. In contrast, intestinal EGF levels increased following CLP, and were further augmented by exogenous EGF treatment. Intestinal EGF-receptor (EGF-R) was increased following CLP whether assayed by immunohistochemistry, real-time PCR or western blot, and exogenous EGF treatment decreased intestinal EGF-R. Villus length decreased 2-fold between sham and septic animals, and EGF treatment resulted in near total restitution of villus length. Sepsis decreased intestinal proliferation and increased intestinal apoptosis. This was accompanied by increased expression of the pro-apoptotic proteins Bid and FADD, as well as the cyclin-dependent kinase inhibitor p21cip1/waf. EGF treatment after the onset of sepsis restored both proliferation and apoptosis to levels seen in sham animals and normalized expression of Bid, FADD, and p21cip1/waf. To determine whether improvements in gut homeostasis were associated with a decrease in sepsis-induced mortality, septic mice with or without EGF treatment after CLP were followed seven days for survival. Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (p<0.05). EGF may thus be a potential therapeutic agent for the treatment of sepsis, in part due to its ability to protect intestinal integrity. PMID:18004230

Implementation of an Inpatient Pediatric Sepsis Identification Pathway.

PubMed

Bradshaw, Chanda; Goodman, Ilyssa; Rosenberg, Rebecca; Bandera, Christopher; Fierman, Arthur; Rudy, Bret

2016-03-01

Early identification and treatment of severe sepsis and septic shock improves outcomes. We sought to identify and evaluate children with possible sepsis on a pediatric medical/surgical unit through successful implementation of a sepsis identification pathway. The sepsis identification pathway, a vital sign screen and subsequent physician evaluation, was implemented in October 2013. Quality improvement interventions were used to improve physician and nursing adherence with the pathway. We reviewed charts of patients with positive screens on a monthly basis to assess for nursing recognition/physician notification, physician evaluation for sepsis, and subsequent physician diagnosis of sepsis and severe sepsis/septic shock. Adherence data were analyzed on a run chart and statistical process control p-chart. Nursing and physician pathway adherence of >80% was achieved over a 6-month period and sustained for the following 6 months. The direction of improvements met standard criteria for special causes. Over a 1-year period, there were 963 admissions to the unit. Positive screens occurred in 161 (16.7%) of these admissions and 38 (23.5%) of these had a physician diagnosis of sepsis, severe sepsis, or septic shock. One patient with neutropenia and septic shock had a negative sepsis screen due to lack of initial fever. Using quality improvement methodology, we successfully implemented a sepsis identification pathway on our pediatric unit. The pathway provided a standardized process to identify and evaluate children with possible sepsis requiring timely evaluation and treatment. Copyright © 2016 by the American Academy of Pediatrics.

Early-onset facioscapulohumeral muscular dystrophy type 1 with some atypical features.

PubMed

Dorobek, Małgorzata; van der Maarel, Silvère M; Lemmers, Richard J L F; Ryniewicz, Barbara; Kabzińska, Dagmara; Frants, Rune R; Gawel, Malgorzata; Walecki, Jerzy; Hausmanowa-Petrusewicz, Irena

2015-04-01

Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes. We present early-onset cases in the Polish population that amounted to 21% of our total population with facioscapulohumeral muscular dystrophy. More than 27% of them presented with severe phenotypes (wheelchair dependency). The residual D4Z4 repeat sizes ranged from 1 to 4 units. In addition, even within early-onset facioscapulohumeral muscular dystrophy type 1 phenotypes, some cases had uncommon features (head drop, early disabling contractures, progressive ptosis, and respiratory insufficiency and cardiomyopathy). © The Author(s) 2014.

Early onset epilepsy is associated with increased mortality: a population-based study

PubMed Central

Moseley, Brian D.; Wirrell, Elaine C.; Wong-Kisiel, Lily C.; Nickels, Katherine

2013-01-01

SUMMARY We examined mortality in early onset (age <12 months) epilepsy in a population-based group of children. Children with early onset epilepsy were significantly more likely to die (case fatality, CF 8/60 versus 8/407, p<0.001; mortality rate, MR 14.5/1000 versus 2/1000 person years; standardized mortality ratio, SMR 22.25 versus 5.67). Mortality was greater in children with malignant neonatal (age <1 month) epilepsy (CF 4/12 versus 12/450, p<0.001; MR 54/1000 person years versus 2.7/1000 person year; SMR 46.55 versus 7.22). Given that only 1/8 early onset epilepsy deaths was seizure-related, mortality appears to be more affected by underlying etiology. PMID:23582606

Automated Detection of Sepsis Using Electronic Medical Record Data: A Systematic Review.

PubMed

Despins, Laurel A

Severe sepsis and septic shock are global issues with high mortality rates. Early recognition and intervention are essential to optimize patient outcomes. Automated detection using electronic medical record (EMR) data can assist this process. This review describes automated sepsis detection using EMR data. PubMed retrieved publications between January 1, 2005 and January 31, 2015. Thirteen studies met study criteria: described an automated detection approach with the potential to detect sepsis or sepsis-related deterioration in real or near-real time; focused on emergency department and hospitalized neonatal, pediatric, or adult patients; and provided performance measures or results indicating the impact of automated sepsis detection. Detection algorithms incorporated systemic inflammatory response and organ dysfunction criteria. Systems in nine studies generated study or care team alerts. Care team alerts did not consistently lead to earlier interventions. Earlier interventions did not consistently translate to improved patient outcomes. Performance measures were inconsistent. Automated sepsis detection is potentially a means to enable early sepsis-related therapy but current performance variability highlights the need for further research.

Development and initial validation of the Classification of Early-Onset Scoliosis (C-EOS).

PubMed

Williams, Brendan A; Matsumoto, Hiroko; McCalla, Daren J; Akbarnia, Behrooz A; Blakemore, Laurel C; Betz, Randal R; Flynn, John M; Johnston, Charles E; McCarthy, Richard E; Roye, David P; Skaggs, David L; Smith, John T; Snyder, Brian D; Sponseller, Paul D; Sturm, Peter F; Thompson, George H; Yazici, Muharrem; Vitale, Michael G

2014-08-20

Early-onset scoliosis is a heterogeneous condition, with highly variable manifestations and natural history. No standardized classification system exists to describe and group patients, to guide optimal care, or to prognosticate outcomes within this population. A classification system for early-onset scoliosis is thus a necessary prerequisite to the timely evolution of care of these patients. Fifteen experienced surgeons participated in a nominal group technique designed to achieve a consensus-based classification system for early-onset scoliosis. A comprehensive list of factors important in managing early-onset scoliosis was generated using a standardized literature review, semi-structured interviews, and open forum discussion. Three group meetings and two rounds of surveying guided the selection of classification components, subgroupings, and cut-points. Initial validation of the system was conducted using an interobserver reliability assessment based on the classification of a series of thirty cases. Nominal group technique was used to identify three core variables (major curve angle, etiology, and kyphosis) with high group content validity scores. Age and curve progression ranked slightly lower. Participants evaluated the cases of thirty patients with early-onset scoliosis for reliability testing. The mean kappa value for etiology (0.64) was substantial, while the mean kappa values for major curve angle (0.95) and kyphosis (0.93) indicated almost perfect agreement. The final classification consisted of a continuous age prefix, etiology (congenital or structural, neuromuscular, syndromic, and idiopathic), major curve angle (1, 2, 3, or 4), and kyphosis (-, N, or +) variables, and an optional progression modifier (P0, P1, or P2). Utilizing formal consensus-building methods in a large group of surgeons experienced in treating early-onset scoliosis, a novel classification system for early-onset scoliosis was developed with all core components demonstrating

Surveillance for outbreaks of influenza-like illness in the institutionalized elderly.

PubMed

Rosewell, A; Chiu, C; Lindley, R; Dwyer, D E; Moffatt, C R M; Shineberg, C; Clarke, E; Booy, R; MacIntyre, C R

2010-08-01

Respiratory outbreaks are common in aged-care facilities (ACFs), are both underreported and frequently identified late, and are often associated with considerable burden of illness and death. There is emerging evidence that active surveillance coupled with early and systematic intervention can reduce this burden. Active surveillance for influenza-like illness and rapid diagnosis of influenza were established in 16 ACFs in Sydney, Australia, prior to the winter of 2006. A point-of-care influenza test and laboratory direct immunofluorescence tests for common respiratory viruses were used for diagnosis. We achieved early identification of seven respiratory disease outbreaks, two of which were caused by influenza. For the influenza outbreaks, antiviral treatment and prophylaxis were initiated 4-6 days from symptom onset in the primary case. A simple active surveillance system for influenza was successfully implemented and resulted in early detection of influenza and other respiratory disease outbreaks. This enabled earlier implementation of prevention and control measures and increased the potential effectiveness of anti-influenza chemoprophylaxis.

Novel Predictors of Sepsis Outperform the American Burn Association Sepsis Criteria in the Burn Intensive Care Unit Patient

DTIC Science & Technology

2013-01-01

increase in insulin requirement over 24 hours; or enteral feeding intol- erance: abdominal distension pr gastric residuals more than two times feeding...performance. However, the inclusion criteria were based on bacteremia (positive blood cul- ture), not coupled with a clinical suspicion of sepsis; only...subtle clinical changes is present in the early stages of infection and sepsis,6 but compiling trends is difficult for busy clinical staff. The

Neural abnormalities in early-onset and adolescence-onset conduct disorder.

PubMed

Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

2010-07-01

Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis.

PubMed

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2018-01-01

Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types A α and A β fibers) with a large conduction velocity (70-120 m/s), and the second component originated from fibers (Type A γ ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders.

Using the integrated nurse leadership program to reduce sepsis mortality.

PubMed

Kliger, Julie; Singer, Sara J; Hoffman, Frank H

2015-06-01

The Integrated Nurse Leadership Program (INLP) is a collaborative improvement model focused on developing practical leadership skills of nurses and other frontline clinicians to lead quality improvement efforts. Sepsis is a major challenge to treat because it arises unpredictably and can progress rapidly. Nine San Francisco Bay Area hospitals participated in a 22-month INLP Sepsis Mortality Reduction Project to improve sepsis detection and management. The INLP focused on developing leadership and process improvement skills of nurses and other frontline clinicians. Teams of trained clinicians then implemented three strategies to improve early identification and timely treatment of sepsis: (1) sepsis screening of all patients, with diagnostic testing according to protocol; (2) timely treatment on the basis of key elements of Early Goal-Directed Therapy (EGDT); and (3) ongoing data review. Each hospital agreed to pursue the goal of reducing sepsis mortality by 15% by the end of the project. In the data collection period (baseline, July-December 2008 and project completion, January-June 2011), team members showed strong improvement in perceived leadership skills, team effectiveness, and ability to improve care quality. During this period, sepsis mortality for eight of the participating hospitals (Hospital 9 joined the project six months after it began) decreased by 43.7%-from 28% in the baseline period to 16% at project completion. Sepsis mortality rates trended downward for all hospitals, significantly decreasing (p<.05 at one hospital, p<.01 for four hospitals). In addition to improvement in safety culture and management of septic patients, hospitals participating in the INLP Sepsis Mortality Reduction Project achieved reductions in sepsis mortality during the study period and sustained reductions for more than one year later. The INLP model can be readily applied beyond sepsis management and mortality to other quality problems.

Early-onset dementias: diagnostic and etiological considerations

PubMed Central

2013-01-01

This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect. PMID:24565469

Early-Onset Physical Frailty in Adults with Diabesity and Peripheral Neuropathy.

PubMed

Tuttle, Lori J; Bittel, Daniel C; Bittel, Adam J; Sinacore, David R

2017-12-07

Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy. We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m 2 ); 13 with diabesity only (53 years of age, BMI 34 kg/m 2 ) and 10 obese controls (67 years of age, BMI 32 kg/m 2 ). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry. Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty. Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Cardiovascular oscillations at the bedside: early diagnosis of neonatal sepsis using heart rate characteristics monitoring

PubMed Central

Moorman, J. Randall; Delos, John B.; Flower, Abigail A.; Cao, Hanqing; Kovatchev, Boris P.; Richman, Joshua S.; Lake, Douglas E.

2014-01-01

We have applied principles of statistical signal processing and non-linear dynamics to analyze heart rate time series from premature newborn infants in order to assist in the early diagnosis of sepsis, a common and potentially deadly bacterial infection of the bloodstream. We began with the observation of reduced variability and transient decelerations in heart rate interval time series for hours up to days prior to clinical signs of illness. We find that measurements of standard deviation, sample asymmetry and sample entropy are highly related to imminent clinical illness. We developed multivariable statistical predictive models, and an interface to display the real-time results to clinicians. Using this approach, we have observed numerous cases in which incipient neonatal sepsis was diagnosed and treated without any clinical illness at all. This review focuses on the mathematical and statistical time series approaches used to detect these abnormal heart rate characteristics and present predictive monitoring information to the clinician. PMID:22026974

Pediatric Sepsis Guidelines: Summary for resource-limited countries

PubMed Central

Khilnani, Praveen; Singhi, Sunit; Lodha, Rakesh; Santhanam, Indumathi; Sachdev, Anil; Chugh, Krishan; Jaishree, M.; Ranjit, Suchitra; Ramachandran, Bala; Ali, Uma; Udani, Soonu; Uttam, Rajiv; Deopujari, Satish

2010-01-01

Justification: Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa. Process: An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products. Objective: To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India. Recommendations: Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3–5 years as new body of evidence accumulates. PMID:20606908

The impact of early-onset cannabis use on functional brain correlates of working memory.

PubMed

Becker, Benjamin; Wagner, Daniel; Gouzoulis-Mayfrank, Euphrosyne; Spuentrup, Elmar; Daumann, Jörg

2010-08-16

Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Distinct breast cancer subtypes in women with early-onset disease across races

PubMed Central

Singh, Mandeep; Ding, Yi; Zhang, Li-Ying; Song, Dong; Gong, Yun; Adams, Sylvia; Ross, Dara S; Wang, Jin-Hua; Grover, Shruti; Doval, Dinesh Chandra; Shao, Charles; He, Zi-Li; Chang, Victor; Chin, Warren W; Deng, Fang-Ming; Singh, Baljit; Zhang, David; Xu, Ru-Liang; Lee, Peng

2014-01-01

Background: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. Methods: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). Results: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. Conclusions: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients. PMID:25057437

Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

PubMed

Immanuel, Jincy; Simmons, David

2017-10-02

We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

Importance of vital signs to the early diagnosis and severity of sepsis: association between vital signs and sequential organ failure assessment score in patients with sepsis.

PubMed

Kenzaka, Tsuneaki; Okayama, Masanobu; Kuroki, Shigehiro; Fukui, Miho; Yahata, Shinsuke; Hayashi, Hiroki; Kitao, Akihito; Sugiyama, Daisuke; Kajii, Eiji; Hashimoto, Masayoshi

2012-01-01

While much attention is given to the fifth vital sign, the utility of the 4 classic vital signs (blood pressure, respiratory rate, body temperature, and heart rate) has been neglected. The aim of this study was to assess a possible association between vital signs and the Sequential Organ Failure Assessment (SOFA) score in patients with sepsis. We performed a prospective, observational study of 206 patients with sepsis. Blood pressure, respiratory rate, body temperature, and heart rate were measured on arrival at the hospital. The SOFA score was also determined on the day of admission. Bivariate correlation analysis showed that all of the vital signs were correlated with the SOFA score. Multiple regression analysis indicated that decreased values of systolic blood pressure (multivariate regression coefficient [Coef] = -0.030, 95% confidence interval [CI] = -0.046 to -0.013) and diastolic blood pressure (Coef = -0.045, 95% CI = -0.070 to -0.019), increased respiratory rate (Coef = 0.176, 95% CI = 0.112 to 0.240), and increased shock index (Coef = 4.232, 95% CI = 2.401 to 6.062) significantly influenced the SOFA score. Increased respiratory rate and shock index were significantly correlated with disease severity in patients with sepsis. Evaluation of these signs may therefore improve early identification of severely ill patients at triage, allowing more aggressive and timely interventions to improve the prognosis of these patients.

Mothers' experience of caring for a child with early onset scoliosis: A qualitative descriptive study.

PubMed

Lauder, Bonnie; Sinclair, Peter M; Maguire, Jane

2018-04-01

This study aimed to identify and describe the experience of parents of children diagnosed with early onset scoliosis living in Australia. Chronic childhood disease has a major impact on health-related quality of life. Caring for a child with a chronic illness is well documented but the specific experiences of parents who care for children with early onset scoliosis, a rare but devastating illness, has not been explored. Numerous studies have described the interrelated psychological, financial, social, physical and logistical factors that impact the experience of the caregiver role with various diseases, but in the case of early onset scoliosis, limited studies have been conducted about the parental experience. A qualitative descriptive design was used. A snowball sampling technique assisted in the recruitment. Parents invited to the study included mothers, fathers and guardians. Data were collected through semistructured interviews and transcribed verbatim. Transcripts were analysed thematically. Data collection complied with the Consolidated criteria for reporting qualitative research guidelines. Twelve mothers of children with early onset scoliosis were interviewed, as only mothers consented to participate. Four major themes emerged: emotional rollercoaster ride, a lack of resources, money talks and pervasive burden. Factors that impacted on the participants' ability to confront, manage and endure caring for a child with early onset scoliosis emerged from the data. The findings suggest there are multiple factors that influence the experience of mothers' caring for a child with early onset scoliosis. The recognition and appropriate management of these factors by healthcare professionals have the potential to improve the quality of life of parents who care for a child with early onset scoliosis. Healthcare professionals have first-line contact with parents of children with early onset scoliosis and are well placed to provide parents with evidence-based education

Clinical diagnosis of sepsis and the combined use of biomarkers and culture- and non-culture-based assays.

PubMed

Bloos, Frank

2015-01-01

Sepsis is among the most common causes of death in hospitalized patients, and early recognition followed by immediate initiation of therapy is an important concept to improve survival in these patients. According to the definition of sepsis, diagnosis of sepsis requires the recognition of the systemic inflammatory response syndrome (SIRS) caused by infection as well as recognition of possible infection-related organ dysfunctions for diagnosis of severe sepsis or septic shock. Both SIRS and organ dysfunctions may occur frequently in hospitalized patients for various reasons. However, the fast recognition of acute infection as a cause of SIRS and newly developed organ dysfunction may be a demanding task since culture-based results of microbiological samples will be available only days after onset of symptoms. Biomarkers and PCR-based pathogen detection may help the physician in differentiating SIRS from sepsis. Procalcitonin (PCT) is the best investigated biomarker for this purpose. Furthermore, the current data support the usage of PCT for guidance of antimicrobial therapy. C-reactive protein (CRP) may be used to monitor the course of infection but has only limited discriminative capabilities. Interleukin-6 is widely used for its fast response to the infectious stimulus, but conclusive data for the application of this biomarker are missing. None of the available biomarkers can by itself reliably differentiate SIRS from sepsis but can aid and shorten the decision process. PCR-based pathogen detection can theoretically shorten the recognition of the underlying pathogen to about 8 h. However, this technique is expensive and requires additional staff in the laboratory; controlled prospective studies are missing. Although current studies suggest that PCR-based pathogen detection may be useful to shorten time to adequate antimicrobial therapy and diagnose invasive Candida infections, no general recommendations about the application of PCR for the diagnosis of sepsis can

Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome.

PubMed

Brodska, Helena; Valenta, Jiri; Pelinkova, Kveta; Stach, Zdenek; Sachl, Robert; Balik, Martin; Zima, Tomas; Drabek, Tomas

2018-03-28

Inflammatory biomarkers may aid to distinguish between systemic inflammatory response syndrome (SIRS) vs. sepsis. We tested the hypotheses that (1) presepsin, a novel biomarker, can distinguish between SIRS and sepsis, and (2) higher presepsin levels will be associated with increased severity of illness and (3) with 28-day mortality, outperforming traditional biomarkers. Procalcitonin (PCT), C-reactive protein (CRP), presepsin, and lactate were analyzed in 60 consecutive patients (sepsis and SIRS, n=30 per group) on day 1 (D1) to D3 (onset sepsis, or after cardiac surgery). The systemic organ failure assessment (SOFA) score was determined daily. There was no difference in mortality in sepsis vs. SIRS (12/30 vs. 8/30). Patients with sepsis had higher SOFA score vs. patients with SIRS (11±4 vs. 8±5; p=0.023), higher presepsin (AUC=0.674; p<0.021), PCT (AUC=0.791; p<0.001), CRP (AUC=0.903; p<0.0001), but not lactate (AUC=0.506; p=0.941). Unlike other biomarkers, presepsin did not correlate with SOFA on D1. All biomarkers were associated with mortality on D1: presepsin (AUC=0.734; p=0.0006; best cutoff=1843 pg/mL), PCT (AUC=0.844; p<0.0001), CRP (AUC=0.701; p=0.0048), and lactate (AUC=0.778; p<0.0001). Multiple regression analyses showed independent associations of CRP with diagnosis of sepsis, and CRP and lactate with mortality. Increased neutrophils (p=0.002) and decreased lymphocytes (p=0.007) and monocytes (p=0.046) were also associated with mortality. Presepsin did not outperform traditional sepsis biomarkers in diagnosing sepsis from SIRS and in prognostication of mortality in critically ill patients. Presepsin may have a limited adjunct value for both diagnosis and an early risk stratification, performing independently of clinical illness severity.

Brain Structure Changes Visualized in Early- and Late-Onset Blind Subjects

PubMed Central

Leporé, Natasha; Voss, Patrice; Lepore, Franco; Chou, Yi-Yu; Fortin, Madeleine; Gougoux, Frédéric; Lee, Agatha D.; Brun, Caroline; Lassonde, Maryse; Madsen, Sarah K.; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

We examine 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor-based morphometry, we map volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject’s structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and hypertrophy in the isthmus. Gains in the isthmus and non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID:19643183

Sepsis and Acute Kidney Injury.

PubMed

Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

2014-12-01

Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer's disease.

PubMed

Schöll, Michael; Ossenkoppele, Rik; Strandberg, Olof; Palmqvist, Sebastian; Jögi, Jonas; Ohlsson, Tomas; Smith, Ruben; Hansson, Oskar

2017-09-01

Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher 18F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher 18F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher 18F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease. © The Author (2017). Published by Oxford

Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

ERIC Educational Resources Information Center

Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.

2010-01-01

Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis

PubMed Central

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2018-01-01

Background Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Materials and methods Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types Aα and Aβ fibers) with a large conduction velocity (70–120 m/s), and the second component originated from fibers (Type Aγ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. Results We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Conclusion Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders. PMID:29731661

Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study

PubMed Central

Acosta, Colleen D.; Kurinczuk, Jennifer J.; Lucas, D. Nuala; Tuffnell, Derek J.; Sellers, Susan; Knight, Marian

2014-01-01

Background In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK. Methods and Findings A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h—and for 24 (75%) women, <9 h—between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%). Conclusions For each maternal sepsis death, approximately 50 women have life-threatening morbidity from

Is 1H NMR metabolomics becoming the promising early biomarker for neonatal sepsis and for monitoring the antibiotic toxicity?

PubMed

Noto, Antonio; Mussap, Michele; Fanos, Vassilios

2014-06-01

Metabolomics, the latest of omics disciplines, has been successfully used in various fields of basic research such as pharmacology and toxicology. Recently, this new science has gained an important role in the translational research of diagnostics. In this regard, the challenge for neonatologists and medical laboratories is to diagnose neonatal sepsis, a disease with high mortality and morbidity due to the difficulty in diagnosing it. Metabolomics, through its ability to identify perturbations caused by this condition, aims at recognizing metabolites that characterize neonatal sepsis with high specificity and sensitivity. The purpose of this review is to highlight the ability of metabolomics to find early biomarkers for this condition, as well as to predict the toxic effects caused by antibiotics.

ASSESSMENT OF OXIDATIVE STRESS IN EARLY AND LATE ONSET PRE-ECLAMPSIA AMONG GHANAIAN WOMEN.

PubMed

Tetteh, P W; Adu-Bonsaffoh, K; Antwi-Boasiako, C; Antwi, D A; Gyan, B; Obed, S A

2015-01-01

Pre-eclampsia is a multisystem pregnancy-related disorder with multiple theories regarding its aetiology resulting in lack of reliable screening tests and well-established measures for primary prevention. However, oxidative stress is increasingly being implicated in the pathogenesi of pre-eclampsia although conflicting findings have been reported. To determine and compare the levels of oxidative stress in early and late onset pre-eclampsia by measuring urinary excretion of isoprostane and total antioxidant power (TAP) in a cohort of pre-eclamptic women at Korle Bu Teaching Hospital. This was a cross-sectional study conducted at Korle-Bu Teaching Hospital, Accra, Ghana involving pre-eclamptic women between the ages 18 and 45 years who gave written informed consent. Urinary isoprostane levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit whereas the Total Anti-oxidant Power in urine samples was determined using Total Antioxidant Power Colorimetric Microplate Assay kit. The data obtained were analyzed using MEGASTAT statistical software package. We included 102 pre-eclamptic women comprising 68 (66.7%) and 34 (33.3%) with early-onset and late-onset pre-eclampsia respectively. There were no statistically significant differences between the mean maternal age, haematological indices, serum ALT, AST, ALT, albumin, urea, creatinine uric acid and total protein at the time of diagnosis. The mean gestational age at diagnosis of early and late onset pre-eclampsia were 31.65 ± 0.41 and 38.03 ± 0.21 respectively (p ˂ 0.001). Also, there were statistically significant differences between the diastolic blood pressure (BP), systolic BP and mean arterial pressure (MAP) at diagnosis of pre-eclampsia in the two categories. The mean urinary Isoprostane excretion was significantly higher in the early onset pre-eclamptic group (3.04 ± 0.34 ng/mg Cr) compared to that of the late onset pre-eclamptic group (2.36 ± 0.45 ng/mg Cr), (p=0.019). Urinary total

Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients.

PubMed

Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2017-08-01

Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases.

PubMed

Chen, Qi; Wang, Yao; Zhao, Min; Hyett, Jonathan; da Silva Costa, Fabricio; Nie, Guiying

2016-07-01

Preeclampsia is a pregnancy specific disorder affecting 3-5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation. Serum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n=16, late-onset n=18) and 66 gestation-age-matched controls, and sera at 11-13weeks of pregnancy from women who later did (n=36) or did not (n=33) develop late-onset preeclampsia, were examined for GDF15 by ELISA. Serum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11-13weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia. Serum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Heart-rate variability depression in porcine peritonitis-induced sepsis without organ failure.

PubMed

Jarkovska, Dagmar; Valesova, Lenka; Chvojka, Jiri; Benes, Jan; Danihel, Vojtech; Sviglerova, Jitka; Nalos, Lukas; Matejovic, Martin; Stengl, Milan

2017-05-01

Depression of heart-rate variability (HRV) in conditions of systemic inflammation has been shown in both patients and experimental animal models and HRV has been suggested as an early indicator of sepsis. The sensitivity of HRV-derived parameters to the severity of sepsis, however, remains unclear. In this study we modified the clinically relevant porcine model of peritonitis-induced sepsis in order to avoid the development of organ failure and to test the sensitivity of HRV to such non-severe conditions. In 11 anesthetized, mechanically ventilated and instrumented domestic pigs of both sexes, sepsis was induced by fecal peritonitis. The dose of feces was adjusted and antibiotic therapy was administered to avoid multiorgan failure. Experimental subjects were screened for 40 h from the induction of sepsis. In all septic animals, sepsis with hyperdynamic circulation and increased plasma levels of inflammatory mediators developed within 12 h from the induction of peritonitis. The sepsis did not progress to multiorgan failure and there was no spontaneous death during the experiment despite a modest requirement for vasopressor therapy in most animals (9/11). A pronounced reduction of HRV and elevation of heart rate developed quickly (within 5 h, time constant of 1.97 ± 0.80 h for HRV parameter TINN) upon the induction of sepsis and were maintained throughout the experiment. The frequency domain analysis revealed a decrease in the high-frequency component. The reduction of HRV parameters and elevation of heart rate preceded sepsis-associated hemodynamic changes by several hours (time constant of 11.28 ± 2.07 h for systemic vascular resistance decline). A pronounced and fast reduction of HRV occurred in the setting of a moderate experimental porcine sepsis without organ failure. Inhibition of parasympathetic cardiac signaling probably represents the main mechanism of HRV reduction in sepsis. The sensitivity of HRV to systemic inflammation may allow

Inter-alpha inhibitor protein administration improves survival from neonatal sepsis in mice.

PubMed

Singh, Kultar; Zhang, Ling Xiu; Bendelja, Kreso; Heath, Ryan; Murphy, Shaun; Sharma, Surendra; Padbury, James F; Lim, Yow-Pin

2010-09-01

Inter-alpha inhibitor proteins (IaIp) are serine proteases inhibitors that modulate endogenous protease activity and have been shown to improve survival in adult models of sepsis. We evaluated the effect of IaIp on survival and systemic responses to sepsis in neonatal mice. Sepsis was induced in 2-d-old mice with lipopolysaccharide (LPS), Escherichia coli, and group B Streptococci. Sepsis was associated with 75% mortality. IaIp, given by i.p. administration at doses between 15 and 45 mg/kg from 1 to 6 h after the onset of sepsis, improved survival to approximately 90% (p = 0.0159) in both LPS-induced sepsis and with live bacterial infections. The greatest effect was on reversal of hemorrhagic pneumonitis. The effects were dose and time dependent. Systemic cytokine profile and tissue histology were examined. Survival was compared in IL-10 knock out animals. Systemic cytokine levels including TNF-[alpha] and IL-10 were increased after induction of sepsis and modulated significantly after IaIp administration. Because the effect of IaIp was still demonstrable in IL-10 deficient mice, we conclude the beneficial effects of IaIp is because of suppression of proinflammatory cytokines such as TNF-[alpha] rather than augmentation of IL-10. IaIp may offer significant benefits as a therapeutic

The global maternal sepsis study and awareness campaign (GLOSS): study protocol.

PubMed

Bonet, Mercedes; Souza, Joao Paulo; Abalos, Edgardo; Fawole, Bukola; Knight, Marian; Kouanda, Seni; Lumbiganon, Pisake; Nabhan, Ashraf; Nadisauskiene, Ruta; Brizuela, Vanessa; Metin Gülmezoglu, A

2018-01-30

Maternal sepsis is the underlying cause of 11% of all maternal deaths and a significant contributor to many deaths attributed to other underlying conditions. The effective prevention, early identification and adequate management of maternal and neonatal infections and sepsis can contribute to reducing the burden of infection as an underlying and contributing cause of morbidity and mortality. The objectives of the Global Maternal Sepsis Study (GLOSS) include: the development and validation of identification criteria for possible severe maternal infection and maternal sepsis; assessment of the frequency of use of a core set of practices recommended for prevention, early identification and management of maternal sepsis; further understanding of mother-to-child transmission of bacterial infection; assessment of the level of awareness about maternal and neonatal sepsis among health care providers; and establishment of a network of health care facilities to implement quality improvement strategies for better identification and management of maternal and early neonatal sepsis. This is a facility-based, prospective, one-week inception cohort study. This study will be implemented in health care facilities located in pre-specified geographical areas of participating countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific. During a seven-day period, all women admitted to or already hospitalised in participating facilities with suspected or confirmed infection during any stage of pregnancy through the 42nd day after abortion or childbirth will be included in the study. Included women will be followed during their stay in the facilities until hospital discharge, death or transfer to another health facility. The maximum intra-hospital follow-up period will be 42 days. GLOSS will provide a set of actionable criteria for identification of women with possible severe maternal infection and maternal sepsis. This study

Indoor tanning and risk of early-onset basal cell carcinoma

PubMed Central

Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

2011-01-01

Background Despite a rise in incidence of basal cell carcinoma (BCC) among young people and the ubiquity of indoor tanning in this population, few epidemiologic studies have investigated this exposure-disease relationship. Objective Evaluate the association between indoor tanning and early-onset BCC. Methods BCC cases (n=376) and controls with minor benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on ever indoor tanning, age of initiation, frequency, duration, burns while tanning, and type of tanning device during an in-person interview. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariate logistic regression with never indoor tanners as the referent group. Results Ever indoor tanning was associated with a 69% increased risk of early-onset BCC (95% CI=1.15-2.48). This association was stronger among women (OR=2.14, 95% CI=1.31-3.47), for multiple BCCs (OR=2.16, 95% CI=1.26-3.70), and for BCCs on the trunk and extremities (OR=2.81, 95% CI=1.57-5.02). Risk increased dose-dependently with years used regular indoor tanning devices (p-trend=0.003), number of overall burns (p-trend=<0.001) and burns to biopsy site (p-trend=<0.001) from indoor tanning. Approximately one-quarter (27%) of early-onset BCCs (or 43% among women) could be prevented if individuals never tanned indoors. Limitations Potential recall bias of indoor tanning by cases and generalizability of the control population suggest replication in other studies is warranted. Conclusions Indoor tanning was a strong risk factor for early-onset BCC, particularly among women. Indoor tanning should continue to be targeted by both policy-based and behavioral interventions, as the impact on BCC-associated morbidity may be substantial. PMID:22153793

Early Onset Diabetes - Genetic And Hormonal Analysis In Pakistani Population.

PubMed

Wahid, Maryam; Kamran, Mohammad

2016-01-01

Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population.

Does theory of mind performance differ in children with early-onset and regressive autism?

PubMed

Matthews, Nicole L; Goldberg, Wendy A; Lukowski, Angela F; Osann, Kathryn; Abdullah, Maryam M; Ly, Agnes R; Thorsen, Kara; Spence, M Anne

2012-01-01

A deficit in theory of mind (ToM), or the ability to infer the mental states of others, has been implicated as one of the major characteristics of Autism Spectrum Disorder (ASD); however, little attention has been devoted to possible differences in ToM ability within ASD. The current study examined ToM performance in children with early-onset autism and regressive autism in comparison to typically developing children. Results indicated that children in the regressive autism group performed significantly better than the early-onset autism group on the non-verbal appearance-reality task. Additionally, Fisher's exact tests indicated a pattern of lowest scores in the early-onset group and highest scores in the typically developing group, whereas the regressive autism group tended to score in between the early-onset and typically developing groups. The apparent heterogeneity in ToM performance within ASD could account for the lack of universality in ToM ability found in previous studies. © 2011 Blackwell Publishing Ltd.

Systolic blood pressure variability in patients with early severe sepsis or septic shock: a prospective cohort study.

PubMed

Tang, Yi; Sorenson, Jeff; Lanspa, Michael; Grissom, Colin K; Mathews, V J; Brown, Samuel M

2017-06-17

Severe sepsis and septic shock are often lethal syndromes, in which the autonomic nervous system may fail to maintain adequate blood pressure. Heart rate variability has been associated with outcomes in sepsis. Whether systolic blood pressure (SBP) variability is associated with clinical outcomes in septic patients is unknown. The propose of this study is to determine whether variability in SBP correlates with vasopressor independence and mortality among septic patients. We prospectively studied patients with severe sepsis or septic shock, admitted to an intensive care unit (ICU) with an arterial catheter. We analyzed SBP variability on the first 5-min window immediately following ICU admission. We performed principal component analysis of multidimensional complexity, and used the first principal component (PC 1 ) as input for Firth logistic regression, controlling for mean systolic pressure (SBP) in the primary analyses, and Acute Physiology and Chronic Health Evaluation (APACHE) II score or NEE dose in the ancillary analyses. Prespecified outcomes were vasopressor independence at 24 h (primary), and 28-day mortality (secondary). We studied 51 patients, 51% of whom achieved vasopressor independence at 24 h. Ten percent died at 28 days. PC 1 represented 26% of the variance in complexity measures. PC 1 was not associated with vasopressor independence on Firth logistic regression (OR 1.04; 95% CI: 0.93-1.16; p = 0.54), but was associated with 28-day mortality (OR 1.16, 95% CI: 1.01-1.35, p = 0.040). Early SBP variability appears to be associated with 28-day mortality in patients with severe sepsis and septic shock.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

PubMed

Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

2013-02-01

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

PubMed

Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

2013-02-01

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de

Isolated early onset anemia after rh isoimmunization: a unique presentation in 3 neonates.

PubMed

Louis, Deepak; Oberoi, Sapna; Sundaram, Venkataseshan; Trehan, Amita

2010-08-01

Rh isoimmunization manifesting as isolated early onset neonatal anemia has not been reported. We describe the presentation of 3 infants who manifested with isolated early severe anemia. All the infants presented early (3 to 7 d of age) with severe pallor. None had clinically significant jaundice. Evidence for hemolysis was present in all and their direct antiglobulin test was positive. To reduce the hemolysis, immunoglobulin was administered after which their hemoglobin improved. This report highlights the possibility of early onset anemia without significant jaundice as the sole manifestation of Rh isoimmunization and the possible beneficial role of immunoglobulin in them.

Initial fractal exponent of heart-rate variability is associated with success of early resuscitation in patients with severe sepsis or septic shock: a prospective cohort study

PubMed Central

Brown, Samuel M.; Tate, Quinn; Jones, Jason P.; Knox, Daniel; Kuttler, Kathryn G.; Lanspa, Michael; Rondina, Matthew T.; Grissom, Colin K.; Behera, Subhasis; Mathews, V.J.; Morris, Alan

2013-01-01

Introduction Heart-rate variability reflects autonomic nervous system tone as well as the overall health of the baroreflex system. We hypothesized that loss of complexity in heart-rate variability upon ICU admission would be associated with unsuccessful early resuscitation of sepsis. Methods We prospectively enrolled patients admitted to ICUs with severe sepsis or septic shock from 2009 to 2011. We studied 30 minutes of EKG, sampled at 500 Hz, at ICU admission and calculated heart-rate complexity via detrended fluctuation analysis. Primary outcome was vasopressor independence at 24 hours after ICU admission. Secondary outcome was 28-day mortality. Results We studied 48 patients, of whom 60% were vasopressor independent at 24 hours. Five (10%) died within 28 days. The ratio of fractal alpha parameters was associated with both vasopressor independence and 28-day mortality (p=0.04) after controlling for mean heart rate. In the optimal model, SOFA score and the long-term fractal alpha parameter were associated with vasopressor independence. Conclusions Loss of complexity in heart rate variability is associated with worse outcome early in severe sepsis and septic shock. Further work should evaluate whether complexity of heart rate variability (HRV) could guide treatment in sepsis. PMID:23958243

Early Immune Function and Duration of Organ Dysfunction in Critically Ill Septic Children.

PubMed

Muszynski, Jennifer A; Nofziger, Ryan; Moore-Clingenpeel, Melissa; Greathouse, Kristin; Anglim, Larissa; Steele, Lisa; Hensley, Josey; Hanson-Huber, Lisa; Nateri, Jyotsna; Ramilo, Octavio; Hall, Mark W

2018-02-22

Late immune suppression is associated with nosocomial infection and mortality in septic adults and children. Relationships between early immune suppression and outcomes in septic children remain unclear. Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis/septic shock. Methods, Measurements and Main Results: Children aged < 18 years meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy controls were sampled once. Innate immune function was quantified by whole blood ex vivo lipopolysaccharide-induced TNFα production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFNγ production capacity. 102 septic children and 35 healthy children were enrolled. Compared to healthy children, septic children demonstrated lower LPS-induced TNFα production (p < 0.0001) and lower PHA-induced IFNγ production (p<0.0001). Among septic children, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction (MODS) and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased MODS days [aRR 1.2 (1.03, 1.5)] and organ dysfunction days [aRR 1.2 (1.1, 1.3)]. Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early suppression of both innate and adaptive immunity are associated with longer duration of organ dysfunction and may be useful markers to guide investigations of immunomodulatory therapies in septic children.

Sepsis and identification of reliable biomarkers for postoperative period prognosis.

PubMed

Siloşi, Cristian Adrian; Siloşi, Isabela; Pădureanu, Vlad; Bogdan, Maria; Mogoantă, Stelian Ştefăniţă; Ciurea, Marius Eugen; Cojocaru, Manole; Boldeanu, Lidia; Avrămescu, Carmen Silvia; Boldeanu, Mihail Virgil; Popa, Dragoş George

2018-01-01

Sepsis is currently defined as the presence of organ dysfunction occurring as the result of a disturbed host response to a serious infection. Sepsis is one of the most common diseases, which cause mortality and a considerable absorber of healthcare resources. Despite progress in technology and improving knowledge of pathophysiology, the disease mechanism is still poorly understood. At present, diagnosis is based on non-specific physiological criteria and on the late identification of the pathogen. For these reasons, the diagnosis may be uncertain, treatment delayed or an immunomodulatory therapy cannot be established. An early and reliable diagnosis is essential to achieve better outcomes on disease progression. The host response to infection involves hundreds of many mediators of which have been proposed as biomarkers. There is a need for new diagnostic approaches for sepsis, new sepsis biomarkers that can aid in diagnosis, therapeutic decision and monitoring of the response to therapy. The differentiation of sepsis from non-infectious systemic inflammatory response syndrome is difficult, and the search for a highly accurate biomarker of sepsis has become one important objective of the medicine. The goal of our review is to summarize the recent advances on the most commonly studied serum biomarkers, evaluated in clinical and experimental studies, for early diagnosis of sepsis and their informative value in diagnosis, prognosis, or response to therapy. In this context, we have tracked the clinical utility of measuring serum biomarkers, such as procalcitonin, pro- and anti-inflammatory cytokines, C-reactive protein, leptin and their combinations. Currently, has not been identified an ideal biomarker to aid in the diagnosis of sepsis. It is hoped that the discovery of new serum markers, as well as their combinations, will serve for the diagnosis and prognosis of sepsis.

Role of presepsin for the evaluation of sepsis in the emergency department.

PubMed

Pizzolato, Elisa; Ulla, Marco; Galluzzo, Claudia; Lucchiari, Manuela; Manetta, Tilde; Lupia, Enrico; Mengozzi, Giulio; Battista, Stefania

2014-10-01

Sepsis, severe sepsis and septic shock are among the most common conditions handled in the emergency department (ED). According to new Sepsis Guidelines, early diagnosis and treatment are the keys to improve survival. Plasma C-reactive protein (CRP) and procalcitonin (PCT) levels, when associated with documented or suspected infection, are now part of the definitions of sepsis. Blood culture is the gold standard method for detecting microorganisms but it requires too much time for results to be known. Sensitive biomarkers are required for early diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. In recent years PCT has been widely used for sepsis differential diagnosis, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. In this mini review we mainly focused on presepsin: we evaluate its diagnostic and prognostic roles in patients presenting to the ED with systemic inflammatory response syndrome (SIRS), suspected sepsis or septic shock.

Variants of early-onset restrictive eating disturbances in middle childhood.

PubMed

Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

2016-01-01

This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. © 2015 Wiley Periodicals, Inc.

Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease

PubMed Central

Sheng, Ke; Fang, Weidong; Zhu, Yingcheng; Shuai, Guangying; Zou, Dezhi; Su, Meilan; Han, Yu; Cheng, Oumei

2016-01-01

HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans.Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state.Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset. Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age. Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset. PMID:27462265

Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis

PubMed Central

Cheyuo, Cletus; Jacob, Asha

2012-01-01

Sepsis, a systemic inflammatory response to infection, continues to carry a high mortality despite advances in critical care medicine. Elevated sympathetic nerve activity in sepsis has been shown to contribute to early hepatocellular dysfunction and subsequently multiple organ failure, resulting in a poor prognosis, especially in the elderly. Thus, suppression of sympathetic nerve activity represents a novel therapeutic option for sepsis. Ghrelin is a 28-amino acid peptide shown to inhibit sympathetic nerve activity and inflammation in animal models of tissue injury. Age-related ghrelin hyporesponsiveness has also been shown to exacerbate sepsis. However, the mechanistic relationship between ghrelin-mediated sympathoinhibition and suppression of inflammation remains poorly understood. This review assesses the therapeutic potential of ghrelin in sepsis in the context of the neuroanatomical and molecular basis of ghrelin-mediated suppression of inflammation through inhibition of central sympathetic outflow. PMID:22068604

CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

PubMed

Elia, M; Falco, M; Ferri, R; Spalletta, A; Bottitta, M; Calabrese, G; Carotenuto, M; Musumeci, S A; Lo Giudice, M; Fichera, M

2008-09-23

To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations. Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis. We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep. This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

Stabilization in early adult-onset myopia with corneal refractive therapy.

PubMed

González-Méijome, José M; Carracedo, Gonzalo; Lopes-Ferreira, Daniela; Faria-Ribeiro, Miguel A; Peixoto-de-Matos, Sofia C; Queirós, António

2016-02-01

To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between -1.50 and -2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ) lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January-December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Global and Temporal Cortical Folding in Patients with Early-Onset Schizophrenia

ERIC Educational Resources Information Center

Penttila, Jani; Paillere-Martinot, Marie-Laure; Martinot, Jean-Luc; Mangin, Jean-Francois; Burke, Lisa; Corrigall, Richard; Frangou, Sophia; Cachia, Arnaud

2008-01-01

Disturbances in the temporal lobes and alterations in cortical folding in adult on-set schizophrenia are studied using magnetic resonance T1 images of 51 patients. The study showed that patients with early on-set schizophrenia had lower global sulcal indices in both hemispheres and the left collateral sulcus has a lower sulcal index irrespective…

Atypical antipsychotics in the treatment of early-onset schizophrenia

PubMed Central

Hrdlicka, Michal; Dudova, Iva

2015-01-01

Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226

Medication sales and syndromic surveillance, France.

PubMed

Vergu, Elisabeta; Grais, Rebecca F; Sarter, Hélène; Fagot, Jean-Paul; Lambert, Bruno; Valleron, Alain-Jaques; Flahault, Antoine

2006-03-01

Although syndromic surveillance systems using nonclinical data have been implemented in the United States, the approach has yet to be tested in France. We present the results of the first model based on drug sales that detects the onset of influenza season and forecasts its trend. Using weekly lagged sales of a selected set of medications, we forecast influenzalike illness (ILI) incidence at the national and regional level for 3 epidemic seasons (2000-01, 2001-02, and 2002-03) and validate the model with real-time updating on the fourth (2003-04). For national forecasts 1-3 weeks ahead, the correlation between observed ILI incidence and forecast was 0.85-0.96, an improvement over the current surveillance method in France. Our findings indicate that drug sales are a useful additional tool to syndromic surveillance, a complementary and independent source of information, and a potential improvement for early warning systems for both epidemic and pandemic planning.

Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

PubMed

Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

2004-09-30

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

Early Identification of Autism: Early Characteristics, Onset of Symptoms, and Diagnostic Stability

ERIC Educational Resources Information Center

Webb, Sara Jane; Jones, Emily J. H.

2009-01-01

In the first year of life, infants who later go on to develop autistic spectrum disorders (ASD) may exhibit subtle disruptions in social interest and attention, communication, temperament, and head circumference growth that occur prior to the onset of clinical symptoms. These disruptions may reflect the early course of ASD development and may also…

Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.

PubMed

Sikich, Linmarie; Frazier, Jean A; McClellan, Jon; Findling, Robert L; Vitiello, Benedetto; Ritz, Louise; Ambler, Denisse; Puglia, Madeline; Maloney, Ann E; Michael, Emily; De Jong, Sandra; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie; Pierson, Leslie; McNamara, Nora K; Delporto-Bedoya, Denise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2008-11-01

Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia

HLA-DR expression, cytokines and bioactive lipids in sepsis

PubMed Central

2014-01-01

Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock. PMID:24904669

Social Status of Adolescents with an Early Onset of Externalizing Behavior: The SNARE Study

ERIC Educational Resources Information Center

Franken, Aart; Harakeh, Zeena; Veenstra, Rene; Vollebergh, Wilma; Dijkstra, Jan Kornelis

2017-01-01

This study investigated the social status (i.e., popularity, likeability, and friendships) of adolescents with an early onset of externalizing behavior (i.e., alcohol use, tobacco use, and antisocial behavior). Building on Moffitt's dual-taxonomy model, it was hypothesized that early onset adolescents were more popular, but not necessarily more…

Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation

NASA Astrophysics Data System (ADS)

Herrmann, I. K.; Bertazzo, S.; O'Callaghan, D. J. P.; Schlegel, A. A.; Kallepitis, C.; Antcliffe, D. B.; Gordon, A. C.; Stevens, M. M.

2015-08-01

Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and

A Multidisciplinary Sepsis Program Enabled by a Two-Stage Clinical Decision Support System: Factors That Influence Patient Outcomes.

PubMed

Amland, Robert C; Haley, James M; Lyons, Jason J

2016-11-01

Sepsis is an inflammatory response triggered by infection, with risk of in-hospital mortality fueled by disease progression. Early recognition and intervention by multidisciplinary sepsis programs may reverse the inflammatory response among at-risk patient populations, potentially improving outcomes. This retrospective study of a sepsis program enabled by a 2-stage sepsis Clinical Decision Support (CDS) system sought to evaluate the program's impact, identify early indicators that may influence outcomes, and uncover opportunities for quality improvement. Data encompassed 16 527 adult hospitalizations from 2014 and 2015. Of 2108 non-intensive care unit patients screened-in by sepsis CDS, 97% patients were stratified by 177 providers. Risk of adverse outcome improved 30% from baseline to year end, with gains materializing and stabilizing at month 7 after sepsis program go-live. Early indicators likely to influence outcomes include patient age, recent hospitalization, electrolyte abnormalities, hypovolemic shock, hypoxemia, patient location when sepsis CDS activated, and specific alert patterns. © The Author(s) 2015.

Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

PubMed Central

2010-01-01

Background Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores. Conclusions Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia. PMID:20509945

[Pharmaconutrition with parenteral selenium in sepsis].

PubMed

Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

2014-04-01

Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Cognitive ability in young adulthood predicts risk of early-onset dementia in Finnish men.

PubMed

Rantalainen, Ville; Lahti, Jari; Henriksson, Markus; Kajantie, Eero; Eriksson, Johan G; Räikkönen, Katri

2018-06-06

To test if the Finnish Defence Forces Basic Intellectual Ability Test scores at 20.1 years predicted risk of organic dementia or Alzheimer disease (AD). Dementia was defined as inpatient or outpatient diagnosis of organic dementia or AD risk derived from Hospital Discharge or Causes of Death Registers in 2,785 men from the Helsinki Birth Cohort Study, divided based on age at first diagnosis into early onset (<65 years) or late onset (≥65 years). The Finnish Defence Forces Basic Intellectual Ability Test comprises verbal, arithmetic, and visuospatial subtests and a total score (scores transformed into a mean of 100 and SD of 15). We used Cox proportional hazard models and adjusted for age at testing, childhood socioeconomic status, mother's age at delivery, parity, participant's birthweight, education, and stroke or coronary heart disease diagnosis. Lower cognitive ability total and verbal ability (hazard ratio [HR] per 1 SD disadvantage >1.69, 95% confidence interval [CI] 1.01-2.63) scores predicted higher early-onset any dementia risk across the statistical models; arithmetic and visuospatial ability scores were similarly associated with early-onset any dementia risk, but these associations weakened after covariate adjustments (HR per 1 SD disadvantage >1.57, 95% CI 0.96-2.57). All associations were rendered nonsignificant when we adjusted for participant's education. Cognitive ability did not predict late-onset dementia risk. These findings reinforce previous suggestions that lower cognitive ability in early life is a risk factor for early-onset dementia. © 2018 American Academy of Neurology.

Bowel sonography in sepsis with pathological correlation: an experimental study.

PubMed

Kim, Hwa-Young; Kim, In-One; Kim, Woo Sun; Kang, Gyeong Hoon

2011-02-01

Sepsis predisposes full-term infants to necrotizing enterocolitis (NEC). As such, experimental induction of NEC was applied to a sepsis model to evaluate the potential role of US in the early diagnosis of NEC in full-term infants. To evaluate the resistive index (RI) of the superior mesenteric artery (SMA) on Doppler sonography in experimentally induced sepsis and correlate it with the pathological findings. Fifteen 1-week-old New Zealand white rabbits (control group n = 3, sepsis group n = 12) were used in this study. We injected 1 mg/kg of E. coli O55-B5 lipopolysaccharide (LPS) into 12 rabbits to induce sepsis. Then we conducted grayscale evaluation of the caliber of the abdominal aorta as well as bowel wall thickness and echogenicity. In addition, we measured peak systolic and end-diastolic velocities and SMA RI on Doppler sonography. Pathological findings were analyzed and correlated with RI readings. Peak systolic and end-diastolic velocities and SMA RI values were analyzed statistically at each hour using the Wilcoxon rank sum test; the control and sepsis groups were compared using the Mann-Whitney test. The bowel wall thickness in the sepsis group was significantly increased after LPS injection. The caliber of the abdominal aorta in the sepsis group was significantly decreased after LPS injection. There were echogenic foci (<10 in axial plane) in the bowel wall after LPS injection. Peak systolic velocity in the sepsis group was not significantly changed, but end-diastolic velocity was decreased. SMA RIs in the sepsis group were significantly increased post-LPS injection from baseline. In the control group there were no significant changes in bowel wall thickness, abdominal aorta caliber, bowel wall echogenicity or peak systolic and end-diastolic velocities and RIs. Pathologically, eight of the 12 rabbits in the sepsis group showed grade 1 intestinal injury, three showed grade 2 injury and one showed grade 3 injury. SMA RIs were higher in grades 2

Biological Terrorism Preparedness: Evaluating the Performance of the Early Aberration Reporting System (EARS) Syndromic Surveillance Algorithms

DTIC Science & Technology

2007-06-01

PREPAREDNESS: EVALUATING THE PERFORMANCE OF THE EARLY ABERRATION REPORTING SYSTEM (EARS) SYNDROMIC SURVEILLANCE ALGORITHMS by David A...SUBTITLE Biological Terrorism Preparedness: Evaluating the Performance of the Early Aberration Reporting System (EARS) Syndromic Surveillance...Algorithms 6. AUTHOR(S) David Dunfee, Benjamin Hegler 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School

Early-Onset Psychosis in Youth with Intellectual Disability

ERIC Educational Resources Information Center

Friedlander, R. I.; Donnelly, T.

2004-01-01

Accurate diagnosis of psychotic disorders may be very difficult in youth with intellectual disabilities. The authors reviewed the assessment, treatment and follow-up of 21 youths with ID referred because of early onset of psychotic symptoms. Just over one half of the patients had a diagnosis of schizophrenia or schizo-affective disorder. One third…

Disease Surveillance on Complex Social Networks

PubMed Central

Herrera, Jose L.; Srinivasan, Ravi; Brownstein, John S.; Galvani, Alison P.; Meyers, Lauren Ancel

2016-01-01

As infectious disease surveillance systems expand to include digital, crowd-sourced, and social network data, public health agencies are gaining unprecedented access to high-resolution data and have an opportunity to selectively monitor informative individuals. Contact networks, which are the webs of interaction through which diseases spread, determine whether and when individuals become infected, and thus who might serve as early and accurate surveillance sensors. Here, we evaluate three strategies for selecting sensors—sampling the most connected, random, and friends of random individuals—in three complex social networks—a simple scale-free network, an empirical Venezuelan college student network, and an empirical Montreal wireless hotspot usage network. Across five different surveillance goals—early and accurate detection of epidemic emergence and peak, and general situational awareness—we find that the optimal choice of sensors depends on the public health goal, the underlying network and the reproduction number of the disease (R0). For diseases with a low R0, the most connected individuals provide the earliest and most accurate information about both the onset and peak of an outbreak. However, identifying network hubs is often impractical, and they can be misleading if monitored for general situational awareness, if the underlying network has significant community structure, or if R0 is high or unknown. Taking a theoretical approach, we also derive the optimal surveillance system for early outbreak detection but find that real-world identification of such sensors would be nearly impossible. By contrast, the friends-of-random strategy offers a more practical and robust alternative. It can be readily implemented without prior knowledge of the network, and by identifying sensors with higher than average, but not the highest, epidemiological risk, it provides reasonably early and accurate information. PMID:27415615

Disease Surveillance on Complex Social Networks.

PubMed

Herrera, Jose L; Srinivasan, Ravi; Brownstein, John S; Galvani, Alison P; Meyers, Lauren Ancel

2016-07-01

As infectious disease surveillance systems expand to include digital, crowd-sourced, and social network data, public health agencies are gaining unprecedented access to high-resolution data and have an opportunity to selectively monitor informative individuals. Contact networks, which are the webs of interaction through which diseases spread, determine whether and when individuals become infected, and thus who might serve as early and accurate surveillance sensors. Here, we evaluate three strategies for selecting sensors-sampling the most connected, random, and friends of random individuals-in three complex social networks-a simple scale-free network, an empirical Venezuelan college student network, and an empirical Montreal wireless hotspot usage network. Across five different surveillance goals-early and accurate detection of epidemic emergence and peak, and general situational awareness-we find that the optimal choice of sensors depends on the public health goal, the underlying network and the reproduction number of the disease (R0). For diseases with a low R0, the most connected individuals provide the earliest and most accurate information about both the onset and peak of an outbreak. However, identifying network hubs is often impractical, and they can be misleading if monitored for general situational awareness, if the underlying network has significant community structure, or if R0 is high or unknown. Taking a theoretical approach, we also derive the optimal surveillance system for early outbreak detection but find that real-world identification of such sensors would be nearly impossible. By contrast, the friends-of-random strategy offers a more practical and robust alternative. It can be readily implemented without prior knowledge of the network, and by identifying sensors with higher than average, but not the highest, epidemiological risk, it provides reasonably early and accurate information.

Mapping callosal morphology in early- and late-onset elderly depression: an index of distinct changes in cortical connectivity.

PubMed

Ballmaier, Martina; Kumar, Anand; Elderkin-Thompson, Virginia; Narr, Katherine L; Luders, Eileen; Thompson, Paul M; Hojatkashani, Cornelius; Pham, Daniel; Heinz, Andreas; Toga, Arthur W

2008-06-01

There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are region-specific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age = 68.00, SD+/-5.83), 22 patients with late-onset depression (mean age = 74.50, SD+/-8.09) and 34 elderly control subjects (mean age = 72.38; SD+/-6.93) were studied. Using 3D MRI data, novel mesh-based geometrical modeling methods were applied to compare the midsagittal thickness of the corpus callosum at high spatial resolution between groups. Neuropsychological correlates of midsagittal callosal area differences were additionally investigated in a subsample of subjects. Depressed patients exhibited significant callosal thinning in the genu and splenium compared to controls. Significant callosal thinning was restricted to the genu in early-onset patients, but patients with late-onset depression exhibited significant callosal thinning in both the genu and splenium relative to controls. The splenium of the corpus callosum was also significantly thinner in subjects with late- vs early-onset depression. Genu and splenium midsagittal areas significantly correlated with memory and attention functioning among late-onset depressed patients, but not early-onset depressed patients or controls. Circumscribed structural alterations in callosal morphology may distinguish late- from early-onset depression in the elderly. These findings suggest distinct abnormalities of cortical connectivity in late- and early-onset elderly depression with possible influence on the course of illness. Patients with a late onset of depression may be at higher risk of illness progression and eventually dementia conversion than early-onset depression, with potentially important implications for research and therapy.

[Treatment of early onset scoliosis : How far can we go?].

PubMed

Studer, D; Hasler, C C; Schulze, A

2015-11-01

Recently, inconsistent definitions of early onset scoliosis (EOS) and a wide variety of treatment options have been observed. To clearly define the term EOS, to depict non-operative and operative treatment options, and to present the limitations of the boundaries of these techniques. Review of the literature, including conference presentations and expert opinions, in addition to personal experiences. Early onset scoliosis (EOS) refers to spine deformity that is present before 10 years of age, regardless of etiology. All existing operative treatment options share a high risk of complications. Therefore, non-operative treatment should act as a time-buying approach to postpone surgery. Awareness of treatment options and their specific indications, in addition to respecting each patient's individual needs and feasibilities, are crucial for the optimal outcome.

Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis

PubMed Central

Kellum, John A.; Kong, Lan; Fink, Mitchell P.; Weissfeld, Lisa A.; Yealy, Donald M.; Pinsky, Michael R.; Fine, Jonathan; Krichevsky, Alexander; Delude, Russell L.; Angus, Derek C.

2015-01-01

Background Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of pro-inflammatory and anti-inflammatory markers, are associated with severe sepsis and death. Methods This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality. Results A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8–39.0) (P<.001). Conclusions The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and

Pediatric Sepsis

PubMed Central

Mathias, Brittany; Mira, Juan; Larson, Shawn D.

2016-01-01

Purpose of Review Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72,000 children hospitalized for sepsis annually with a reported mortality rate of 25% and an economic cost estimated to be $4.8 billion. However, it is only recently that the definition and management of pediatric sepsis has been recognized as being distinct from adult sepsis. Recent Findings The definition of pediatric sepsis is currently in a state of evolution and there is a large disconnect between the clinical and research definitions of sepsis which impacts the application of research findings into clinical practice. Despite this, it is the speed of diagnosis and the timely implementation of current treatment guidelines that has been shown to improve outcomes. However, adherence to treatment guidelines is currently low and it is only through the implementation of protocols that improved care and outcomes have been demonstrated. Summary Current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment; however, distinct physiology demands more prospective pediatric trials to tailor management to the pediatric population. Adherence to current and emerging practice guidelines will require that protocolized care pathways become commonplace. PMID:26983000

Pediatric sepsis.

PubMed

Mathias, Brittany; Mira, Juan C; Larson, Shawn D

2016-06-01

Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72 000 children hospitalized for sepsis annually with a reported mortality rate of 25% and an economic cost estimated to be $4.8 billion. However, it is only recently that the definition and management of pediatric sepsis has been recognized as being distinct from adult sepsis. The definition of pediatric sepsis is currently in a state of evolution, and there is a large disconnect between the clinical and research definitions of sepsis which impacts the application of research findings into clinical practice. Despite this, it is the speed of diagnosis and the timely implementation of current treatment guidelines that has been shown to improve outcomes. However, adherence to treatment guidelines is currently low and it is only through the implementation of protocols that improved care and outcomes have been demonstrated. The current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment; however, distinct physiology demands more prospective pediatric trials to tailor management to the pediatric population. Adherence to current and emerging practice guidelines will require that protocolized care pathways become a commonplace.

Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.

PubMed

Belcastro, Vincenzo; Caraballo, Roberto Horacio; Romeo, Antonino; Striano, Pasquale

2013-12-01

Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

N-acetylcysteine for sepsis and systemic inflammatory response in adults.

PubMed

Szakmany, Tamas; Hauser, Balázs; Radermacher, Peter

2012-09-12

Death is common in systemic inflammatory response syndrome (SIRS) or sepsis-induced multisystem organ failure and it has been thought that antioxidants such as N-acetylcysteine could be beneficial. We assessed the clinical effectiveness of intravenous N-acetylcysteine for the treatment of patients with SIRS or sepsis. We searched the following databases: Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue 12); MEDLINE (January 1950 to January 2012); EMBASE (January 1980 to January 2012); CINAHL (1982 to January 2012); the NHS Trusts Clinical Trials Register and Current Controlled Trials (www.controlled-trials.com); LILACS; KoreaMED; MEDCARIB; INDMED; PANTELEIMON; Ingenta; ISI Web of Knowledge and the National Trials Register to identify all relevant randomized controlled trials available for review. We included only randomized controlled trials (RCTs) in the meta-analysis. We independently performed study selection, quality assessment and data extraction. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We included 41 fully published studies (2768 patients). Mortality was similar in the N-acetylcysteine group and the placebo group (RR 1.06, 95% CI 0.79 to 1.42; I(2) = 0%). Neither did N-acetylcysteine show any significant effect on length of stay, duration of mechanical ventilation or incidence of new organ failure. Early application of N-acetylcysteine to prevent the development of an oxidato-inflammatory response did not affect the outcome, nor did late application that is after 24 hours of developing symptoms. Late application was associated with cardiovascular instability. Overall, this meta-analysis puts doubt on the safety and utility of intravenous N-acetylcysteine as an adjuvant therapy in SIRS and sepsis. At best, N-acetylcysteine is ineffective in reducing mortality and complications in this patient population. At worst, it can be harmful

Inter-Alpha Inhibitor Protein (IAIP) Administration Improves Survival From Neonatal Sepsis In Mice

PubMed Central

Singh, Kultar; Zhang, Ling Xiu; Bendelja, Kreso; Heath, Ryan; Murphy, Shaun; Sharma, Surendra; Padbury, James F.; Lim, Yow-Pin

2010-01-01

Inter-alpha Inhibitor proteins (IaIp) are serine proteases inhibitors which modulate endogenous protease activity and have been shown to improve survival in adult models of sepsis. We evaluated the effect of IaIp on survival and systemic responses to sepsis in neonatal mice. Sepsis was induced in 2-day-old mice with LPS, E. coli and Group B Streptococci. Sepsis was associated with 75% mortality. IaIp, given by intraperitoneal administration at doses between 15–45 mg/kg from 1–6 hours following the onset of sepsis improved survival to nearly 90% (p = 0.0159) in both LPS induced sepsis and with live bacterial infections. The greatest effect was on reversal of hemorrhagic pneumonitis. The effects were dose and time dependent. Systemic cytokine profile and tissue histology were examined. Survival was compared in interleukin 10 knock out animals. Systemic cytokine levels, including TNF-α and IL-10 were increased following induction of sepsis and modulated significantly following IaIp administration. Because the effect of IaIp was still demonstrable in IL-10 deficient mice, we conclude the beneficial effect(s) of IaIp is due to suppression of pro-inflammatory cytokines like TNF-α rather than augmentation of IL-10. IaIp may offer significant benefits as a therapeutic adjunct to treatment of sepsis in neonates and adults. PMID:20520583

Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia.

PubMed

Boyd, Heather A; Tahir, Hassaan; Wohlfahrt, Jan; Melbye, Mads

2013-12-01

Preeclampsia encompasses multiple conditions of varying severity. We examined the recurrence and familial aggregation of preeclampsia by timing of onset, which is a marker for severity. We ascertained personal and family histories of preeclampsia for women who delivered live singletons in Denmark in 1978-2008 (almost 1.4 million pregnancies). Using log-linear binomial regression, we estimated risk ratios for the associations between personal and family histories of preeclampsia and the risk of early-onset (before 34 weeks of gestation, which is typically the most severe), intermediate-onset (at 34-36 weeks of gestation), and late-onset (after 36 weeks of gestation) preeclampsia. Previous early-, intermediate-, or late-onset preeclampsia increased the risk of recurrent preeclampsia with the same timing of onset 25.2 times (95% confidence interval (CI): 21.8, 29.1), 19.7 times (95% CI: 17.0, 22.8), and 10.3 times (95% CI: 9.85, 10.9), respectively, compared with having no such history. Preeclampsia in a woman's family was associated with a 24%-163% increase in preeclampsia risk, with the strongest associations for early- and intermediate-onset preeclampsia in female relatives. Preeclampsia in the man's family did not affect a woman's risk of early-onset preeclampsia and was only weakly associated with her risks of intermediate- and late-onset preeclampsia. Early-onset preeclampsia appears to have the largest genetic component, whereas environmental factors likely contribute most to late-onset preeclampsia. The role of paternal genes in the etiology of preeclampsia appears to be limited.

Practices related to late-onset sepsis in very low-birth weight preterm infants.

PubMed

Bentlin, Maria Regina; Rugolo, Ligia M S S; Ferrari, Ligia S L

2015-01-01

To understand the practices related to late-onset sepsis (LOS) in the centers of the Brazilian Neonatal Research Network, and to propose strategies to reduce the incidence of LOS. This was a cross-sectional descriptive multicenter study approved by the Ethics Committee. Three questionnaires regarding hand hygiene, vascular catheters, and diagnosis/treatment of LOS were sent to the coordinator of each center. The center with the lowest incidence of LOS was compared with the others. All 16 centers answered the questionnaires. Regarding hand hygiene, 87% use chlorhexidine or 70% alcohol; alcohol gel is used in 100%; 80% use bedside dispensers (50% had one dispenser for every two beds); practical training occurs in 100% and theoretical training in 70% of the centers, and 37% train once a year. Catheters: 94% have a protocol, and 75% have a line insertion team. Diagnosis/treatment: complete blood count and blood culture are used in 100%, PCR in 87%, hematological scores in 75%; oxacillin and aminoglycosides is the empirical therapy in 50% of centers. Characteristics of the center with lowest incidence of LOS: stricter hand hygiene; catheter insertion and maintenance groups; use of blood culture, PCR, and hematological score for diagnosis; empirical therapy with oxacillin and aminoglycoside. The knowledge of the practices of each center allowed for the identification of aspects to be improved as a strategy to reduce LOS, including: alcohol gel use, hand hygiene training, implementation of catheter teams, and wise use of antibiotic therapy. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Exome Sequencing Frequently Reveals the Cause of Early-Onset Chronic Kidney Disease

PubMed Central

Vivante, Asaf; Hildebrandt, Friedhelm

2016-01-01

The primary causes of chronic kidney disease (CKD) in children differ from those of adult onset CKD. In the United States the most common diagnostic groups of CKD that manifests before 25 years of age are: i) congenital anomalies of the kidneys and urinary tract (CAKUT) (49.1%), ii) steroid-resistant nephrotic syndrome (SRNS) (10.4%), iii) chronic glomerulonephritis (8.1%), and iv) renal cystic ciliopathies (5.3 %), encompassing >70% of CKD together. Recent findings suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. High-throughput sequencing has very recently rendered identification of causative mutations in this high number of genes feasible. Molecular genetic diagnostics in early onset-CKD (before the age of 25 years) will, i) provide patients and families with a molecular genetic diagnosis, ii) generate new insights into diseases mechanisms, iii) allow etiology-based classification of patient cohorts for clinical studies and, iv) may have consequences for personalized treatment and prevention of CKD. In this review, we will discuss the implications of next-generation sequencing for clinical genetic diagnostics and discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and therapeutic implications. PMID:26750453

The New Sepsis Definitions: Implications for the Basic and Translational Research Communities.

PubMed

Coopersmith, Craig M; Deutschman, Clifford S

2017-03-01

New definitions of sepsis and septic shock were published in early 2016, updating old definitions that have not been revisited since 2001. These new definitions should profoundly affect sepsis research. In addition, these papers present clinical criteria for identifying infected patients who are highly likely to have or to develop sepsis or septic shock. In contrast to previous approaches, these new clinical criteria are evidence based. In this review, two of the authors of the new definitions detail the content of the papers and explore the implications for shock and sepsis researchers.

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

PubMed

Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

2017-12-01

To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

Procalcitonin, C-reactive protein and serum lactate dehydrogenase in the diagnosis of bacterial sepsis, SIRS and systemic candidiasis.

PubMed

Miglietta, Fabio; Faneschi, Maria Letizia; Lobreglio, Giambattista; Palumbo, Claudio; Rizzo, Adriana; Cucurachi, Marco; Portaccio, Gerolamo; Guerra, Francesco; Pizzolante, Maria

2015-09-01

The aim of this study was to evaluate procalcitonin (PCT), C-reactive protein (CRP), platelet count (PLT) and serum lactate dehydrogenase (LDH) as early markers for diagnosis of SIRS, bacterial sepsis and systemic candidiasis in intensive care unit (ICU) patients. Based on blood culture results, the patients were divided into a sepsis group (70 patients), a SIRS group (42 patients) and a systemic candidiasis group (33 patients). PCT, CRP, LDH and PLT levels were measured on day 0 and on day 2 from the sepsis symptom onset. PCT levels were higher in Gram negative sepsis than those in Gram positive sepsis, although the P value between the two subgroups is not significant (P=0.095). Bacterial sepsis group had higher PCT and CRP levels compared with the systemic candidiasis group, whereas PLT and LDH levels showed similar levels in these two subgroups. The AUC for PCT (AUC: 0.892, P <0.001) was larger than for CRP (AUC: 0.738, P <0.001). The best cut-off values for PCT and CRP were 0.99 ng/mL and 76.2 mg/L, respectively. Diagnostic sensitivity and specificity for PCT were 84.3% and 81.8% whereas CRP showed a sensitivity of 77.2% and a specificity of 63.6%. However, PCT was unable to discriminate between SIRS and systemic candidiasis groups (P=0.093 N.S.). In conclusion, PCT can be used as a preliminary marker in the event of clinical suspicion of systemic candidiasis; however, low PCT levels (<0.99 ng/mL) necessarily require the use of other specific markers of candidaemia to confirm the diagnosis, due to great uniformity of PCT levels in systemic candidiasis and SIRS groups.

Rethinking the concept of sepsis and septic shock.

PubMed

A Cabrita, Joana; Pinheiro, Isabel; Menezes Falcão, L

2018-06-16

Sepsis is a major global health problem and represents a challenge for physicians all over the world. The knowledge of sepsis and septic shock is a topic of interest among the scientific community and society in general. New guidelines for management of sepsis and septic shock were developed in 2016, providing an update on this area. In Sepsis-3 new definitions for sepsis and septic shock were published. The purpose of this narrative review is to discuss and compare the new criteria of 2016 with the old criteria, purposing at the same time an alternative approach for this topic. SOFA criteria (Sequential Organ Failure Assessment Score) are more complete, but too extensive and usually difficult to apply outside the intensive care units, therefore inducing potentially delay in the proper treatment. We purpose combined criteria for the selection of sepsis patients. Initially, we could apply qSOFA (quick Sepsis Related Organ Failure Assessment) criteria, due to its easy application, associated with the SIRS (systemic inflammatory response syndrome) criteria, allowing to select the patients who are infected and need faster treatment. In that way we would use the best of old and newest criteria, allowing the early selection of patients who are infected and require faster treatment, while the search for a better and faster tool continues. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Sepsis Fact Sheet

MedlinePlus

... News & Meetings Science Education About NIGMS NIGMS Home > Science Education > Sepsis Sepsis Tagline (Optional) Middle/Main Content Area PDF Version (392 KB) En español Other Fact Sheets What is sepsis? Sepsis is a serious ...

The impact of patent ductus arteriosus in neonates with late onset sepsis: a retrospective matched-case control study.

PubMed

Chiang, Pei-Jung; Hsu, Jen-Fu; Tsai, Ming-Horng; Lien, Reyin; Chiang, Ming-Chou; Huang, Hsuan-Rong; Chiang, Chiao-Ching; Liang, Hwey-Fang; Chu, Shih-Ming

2012-10-01

Late-onset sepsis (LOS) in neonates with patent ductus arteriosus (PDA) may predispose them to more complicated hospital courses. The objective of this study was to determine the incidence, the distribution of pathogens, and the clinical features of LOS in neonates with PDA and analyze their outcomes. The medical records were reviewed retrospectively of infants with PDA and LOS who were hospitalized in NICUs of Chang Gung Children's Hospital between January 2003 and December 2009. The clinical features of these infants were compared with a group of gestational age and birth body weight-matched neonates with LOS during the same period. During this period, 224 neonates were found to have at least one event of blood-culture proven LOS and 79 (35.3%) were documented to have PDA. Although most LOS episodes (85/104, 81.7%) in neonates with PDA occurred after closure of PDA, neonates with PDA had a significantly higher rate of bronchopulmonary dysplasia (81.0% vs. 61.0%, p = 0.002) and a relatively higher rate of recurrent sepsis (25.3% vs. 15.2%, p = 0.079) than those without PDA. Longer durations of ventilator support and hospital stay were also noted in neonates with PDA as compared to those without (p = 0.001 and 0.005, respectively). In neonates with LOS, the presence of PDA, even though it is aggressively treated with indomethacin or surgical intervention, may still contribute to the complexity of hospitalization. Close monitoring and aggressive treatments are warranted in these neonates with PDA. Copyright © 2012. Published by Elsevier B.V.

Comparison of Neuropsychological Functioning Between Adults With Early- and Late-Onset DSM-5 ADHD.

PubMed

Lin, Yu-Ju; Gau, Susan Shur-Fen

2017-09-01

We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and non-ADHD controls. We divided the participants, aged 17 to 40 years, into three groups-(a) ADHD, onset <7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls ( n = 148)-and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing Automated Battery. Both ADHD groups had deficits in attention and signal detectability, spatial working memory, and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups in neuropsychological functioning. DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

Sepsis (For Parents)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Sepsis KidsHealth / For Parents / Sepsis What's in this article? ... When to Call the Doctor Print What Is Sepsis? Sepsis is when the immune system responds to ...

Whole Exome Analysis of Early Onset Alzheimer’s Disease

DTIC Science & Technology

2016-04-01

Early Onset Alzheimer’s Disease 5a. CONTRACT NUMBER W81XWH-12-1-0013 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Margaret A. Pericak...relationship between SORL1, AD, and Parkinsonism . 16 Appendix V: ABCA7 Frameshift Deletion Associated with Alzheimer’s Disease in African Americans...onset Alzheimer disease identified using whole-exome sequencing G. W. Beecham1, B. W. Kunkle1, B. Vardarajan2, P. L. Whitehead1, S . Rolati1, E. R

[New Concept for Surviving Sepsis: from Phenomenon to Essence].

PubMed

Liao, Xue-Lian; Xie, Zhi-Chao; Kang, Yan

2016-07-01

Sepsis is a critical clinical syndrome which keep puzzling the medical profession for many years. Recently, the results from several large-scale trials challenged the necessity of early goal directed therapy (EGDT) in surviving sepsis bundle, These trials were not opposed to EGDT but bring new concept that it is essential to utilize therapy with multiple monitoring measures in order to minimize injury while guarantee the safety . Deeper understanding in the pathogenesis of sepsis gives rise to the update of its definition based on vital organ dysfunction. The importance of dynamic monitoring in defining sepsis also need to be emphasized. Developing more effective monitoring measures could provide better treatments, thus improve the prognosis of septic patients. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

The potential of gut microbiota and fecal volatile organic compounds analysis as early diagnostic biomarker for necrotizing enterocolitis and sepsis in preterm infants.

PubMed

Berkhout, Daniel Johannes Cornelis; Niemarkt, Hendrik Johannes; de Boer, Nanne Klaas Hendrik; Benninga, Marc Alexander; de Meij, Timotheüs Gualtherus Jacob

2018-05-01

Although the exact pathophysiological mechanisms of both necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants are yet to be elucidated, evidence is emerging that the gut microbiota plays a key role in their pathophysiology. Areas covered: In this review, initial microbial colonization and factors influencing microbiota composition are discussed. For both NEC and LOS, an overview of studies investigating preclinical alterations in gut microbiota composition and fecal volatile organic compounds (VOCs) is provided. Fecal VOCs are considered to reflect not only gut microbiota composition, but also their metabolic activity and concurrent interaction with the host. Expert review: Heterogeneity in study protocols and applied analytical techniques hampers reliable comparison between outcomes of different microbiota studies, limiting the ability to draw firm conclusions. This dilemma is illustrated by the finding that study results often cannot be reproduced, or even contradict each other. A NEC- and sepsis specific microbial or metabolic signature has not yet been discovered. Identification of 'disease-specific' VOCs and microbiota composition may increase understanding on pathophysiological mechanisms and may allow for development of an accurate screening tool, opening avenues towards timely identification and initiation of targeted treatment for preterm infants at increased risk for NEC and sepsis.

Evidence for apolipoprotein E {epsilon}4 association in early-onset Alzheimer`s patients with late-onset relatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez-Tur, J.; Delacourte, A.; Chartier-Harlin, M.C.

1995-12-18

Recently several reports have extended the apolipoprotein E (APOE) {epsilon}4 association found in late-onset Alzheimer`s disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset {<=}60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE {epsilon}A allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that, for an individual, bearing at least one {epsilon}4 allele increases both the risk of AD beforemore » age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases. 19 refs., 3 tabs.« less

Pediatric Sepsis.

PubMed

Prusakowski, Melanie K; Chen, Audrey P

2017-02-01

Pediatric sepsis is distinct from adult sepsis in its definitions, clinical presentations, and management. Recognition of pediatric sepsis is complicated by the various pediatric-specific comorbidities that contribute to its mortality and the age- and development-specific vital sign and clinical parameters that obscure its recognition. This article outlines the clinical presentation and management of sepsis in neonates, infants, and children, and highlights some key populations who require specialized care. Copyright © 2016 Elsevier Inc. All rights reserved.

Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines.

PubMed

Herrán-Monge, Rubén; Muriel-Bombín, Arturo; García-García, Marta M; Merino-García, Pedro A; Martínez-Barrios, Miguel; Andaluz, David; Ballesteros, Juan Carlos; Domínguez-Berrot, Ana María; Moradillo-Gonzalez, Susana; Macías, Santiago; Álvarez-Martínez, Braulio; Fernández-Calavia, M José; Tarancón, Concepción; Villar, Jesús; Blanco, Jesús

2017-01-01

To determine the epidemiology and outcome of severe sepsis and septic shock after 9 years of the implementation of the Surviving Sepsis Campaign (SSC) and to build a mortality prediction model. This is a prospective, multicenter, observational study performed during a 5-month period in 2011 in a network of 11 intensive care units (ICUs). We compared our findings with those obtained in the same ICUs in a study conducted in 2002. The current cohort included 262 episodes of severe sepsis and/or septic shock, and the 2002 cohort included 324. The prevalence was 14% (95% confidence interval: 12.5-15.7) with no differences to 2002. The population-based incidence was 31 cases/100 000 inhabitants/year. Patients in 2011 had a significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II; 21.9 ± 6.6 vs 25.5 ± 7.07), Logistic Organ Dysfunction Score (5.6 ± 3.2 vs 6.3 ± 3.6), and Sequential Organ Failure Assessment (SOFA) scores on day 1 (8 ± 3.5 vs 9.6 ± 3.7; P < .01). The main source of infection was intraabdominal (32.5%) although microbiologic isolation was possible in 56.7% of cases. The 2011 cohort had a marked reduction in 48-hour (7% vs 14.8%), ICU (27.2% vs 48.2%), and in-hospital (36.7% vs 54.3%) mortalities. Most relevant factors associated with death were APACHE II score, age, previous immunosuppression and liver insufficiency, alcoholism, nosocomial infection, and Delta SOFA score. Although the incidence of sepsis/septic shock remained unchanged during a 10-year period, the implementation of the SSC guidelines resulted in a marked decrease in the overall mortality. The lower severity of patients on ICU admission and the reduced early mortality suggest an improvement in early diagnosis, better initial management, and earlier antibiotic treatment.

Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

PubMed

Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

2015-01-01

After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

Sepsis National Hospital Inpatient Quality Measure (SEP-1): Multistakeholder Work Group Recommendations for Appropriate Antibiotics for the Treatment of Sepsis.

PubMed

Septimus, Edward J; Coopersmith, Craig M; Whittle, Jessica; Hale, Caleb P; Fishman, Neil O; Kim, Thomas J

2017-10-16

The Center for Medicare and Medicaid Services adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting Program in July 2015 to help address the high mortality and high cost associated with sepsis. The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multistakeholder workgroup recognizes the need for SEP-1 but strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, is not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the workgroup provides recommendations for appropriate antibiotics for the treatment of sepsis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

PubMed

Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

2018-04-15

Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

Monitoring sepsis using electrical cell profiling.

PubMed

Prieto, Javier L; Su, Hao-Wei; Hou, Han Wei; Vera, Miguel Pinilla; Levy, Bruce D; Baron, Rebecca M; Han, Jongyoon; Voldman, Joel

2016-11-01

Sepsis is a potentially lethal condition that may be ameliorated through early monitoring of circulating activated leukocytes for faster stratification of severity of illness and improved administration of targeted treatment. Characterization of the intrinsic electrical properties of leukocytes is label-free and can provide a quick way to quantify the number of activated cells as sepsis progresses. Iso-dielectric separation (IDS) uses dielectrophoresis (DEP) to characterize the electrical signatures of cells. Here, we use IDS to show that activated and non-activated leukocytes have different electrical properties. We then present a double-sided version of the IDS platform to increase throughput to characterize thousands of cells. This new platform is less prone to cell fouling and allows faster characterization. Using peripheral blood samples from a cecal ligation and puncture (CLP) model of polymicrobial sepsis in mice, we estimate the number of activated leukocytes by looking into differences in the electrical properties of cells. We show for the first time using animal models that electrical cell profiling correlates with flow cytometry (FC) results and that IDS is therefore a good candidate for providing rapid monitoring of sepsis by quantifying the number of circulating activated leukocytes.

Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014

PubMed Central

Dantes, Raymund; Epstein, Lauren; Murphy, David J.; Seymour, Christopher W.; Iwashyna, Theodore J.; Kadri, Sameer S.; Angus, Derek C.; Danner, Robert L.; Fiore, Anthony E.; Jernigan, John A.; Martin, Greg S.; Septimus, Edward; Warren, David K.; Karcz, Anita; Chan, Christina; Menchaca, John T.; Wang, Rui; Gruber, Susan; Klompas, Michael

2017-01-01

Importance Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (−3.3%/y [95% CI, −5.6% to −1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (�

Neonatal sepsis in rural India: timing, microbiology, and antibiotic resistance in a population-based prospective study in the community setting

PubMed Central

Panigrahi, Pinaki; Chandel, Dinesh S.; Hansen, Nellie I.; Sharma, Nidhi; Kandefer, Sarah; Parida, Sailajanandan; Satpathy, Radhanath; Pradhan, Lingaraj; Mohapatra, Arjit; Mohapatra, Subhranshu S.; Misra, Pravas R.; Banaji, Nandita; Johnson, Judith A.; Morris, John Glenn; Gewolb, Ira H.; Chaudhry, Rama

2017-01-01

Objective To examine the timing and microbiology of neonatal sepsis in a population-based surveillance in the Indian community setting. Study Design All live born infants in 223 villages of Odisha state were followed at home for 60 days. Suspect sepsis cases were referred to study hospitals for further evaluation including blood culture. Results Of 12,622 births, 842 were admitted with suspected sepsis of whom 95% were 4–60 days old. Culture confirmed incidence of sepsis was 6.7/1000 births with 51% Gram negatives (Klebsiella predominating) and 26% Gram positives (mostly Staphylococcus aureus). A very high level of resistance to penicillin and ampicillin, moderate resistance to cephalosporins, and extremely low resistance to Gentamicin and Amikacin was observed. Conclusion The bacterial burden of sepsis in the Indian community is not high. Judicious choice of empiric antibiotics, antibiotic stewardship, and alternate modalities should be considered for the management or prevention of neonatal sepsis in India. PMID:28492525

Sepsis

MedlinePlus

Septicemia; Sepsis syndrome; Systemic inflammatory response syndrome; SIRS; Septic shock ... The symptoms of sepsis are not caused by the germs themselves. Instead, chemicals the body releases cause the response. A bacterial infection anywhere ...

Pregnancy-related group a streptococcal infections: temporal relationships between bacterial acquisition, infection onset, clinical findings, and outcome.

PubMed

Hamilton, Stephanie M; Stevens, Dennis L; Bryant, Amy E

2013-09-01

Puerperal sepsis caused by group A Streptococcus (GAS) remains an important cause of maternal and infant mortality worldwide, including countries with modern antibiotic regimens, intensive care measures and infection control practices. To provide insights into the genesis of modern GAS puerperal sepsis, we reviewed the published cases and case series from 1974 to 2009, specifically seeking relationships between the likely source of pathogen acquisition, clinical signs, and symptoms at infection onset and patient outcomes that could provide clues for early diagnosis. Results suggest that the pathogenesis of pregnancy-related GAS infections in modern times is complex and not simply the result of exposure to GAS in the hospital setting. Additional research is needed to further explore the source of GAS, the specific M types involved, and the pathogenesis of these pregnancy-related infections to generate novel preventative and therapeutic strategies.

Pregnancy-Related Group A Streptococcal Infections: Temporal Relationships Between Bacterial Acquisition, Infection Onset, Clinical Findings, and Outcome

PubMed Central

Hamilton, Stephanie M.; Stevens, Dennis L.; Bryant, Amy E.

2013-01-01

Puerperal sepsis caused by group A Streptococcus (GAS) remains an important cause of maternal and infant mortality worldwide, including countries with modern antibiotic regimens, intensive care measures and infection control practices. To provide insights into the genesis of modern GAS puerperal sepsis, we reviewed the published cases and case series from 1974 to 2009, specifically seeking relationships between the likely source of pathogen acquisition, clinical signs, and symptoms at infection onset and patient outcomes that could provide clues for early diagnosis. Results suggest that the pathogenesis of pregnancy-related GAS infections in modern times is complex and not simply the result of exposure to GAS in the hospital setting. Additional research is needed to further explore the source of GAS, the specific M types involved, and the pathogenesis of these pregnancy-related infections to generate novel preventative and therapeutic strategies. PMID:23645851

Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

PubMed

Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

2018-01-01

To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

ERIC Educational Resources Information Center

Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.

2009-01-01

Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening.

PubMed

Daix, Thomas; Guerin, Estelle; Tavernier, Elsa; Mercier, Emmanuelle; Gissot, Valérie; Hérault, Olivier; Mira, Jean-Paul; Dumas, Florence; Chapuis, Nicolas; Guitton, Christophe; Béné, Marie C; Quenot, Jean-Pierre; Tissier, Cindy; Guy, Julien; Piton, Gaël; Roggy, Anne; Muller, Grégoire; Legac, Éric; de Prost, Nicolas; Khellaf, Mehdi; Wagner-Ballon, Orianne; Coudroy, Rémi; Dindinaud, Elodie; Uhel, Fabrice; Roussel, Mikaël; Lafon, Thomas; Jeannet, Robin; Vargas, Frédéric; Fleureau, Catherine; Roux, Mickaël; Allou, Kaoutar; Vignon, Philippe; Feuillard, Jean; François, Bruno

2018-04-26

In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64 pos granulocytes, CD16 pos monocytes, CD16 dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center. Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64 pos granulocytes, CD16 pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death. Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration. ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

The common single-nucleotide polymorphism rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

PubMed

Wan, Ji-Peng; Wang, Hong; Li, Chang-Zhong; Zhao, Han; You, Li; Shi, Dong-Hong; Sun, Xiu-Hua; Lv, Hong; Wang, Fei; Wen, Ze-Qing; Wang, Xie-Tong; Chen, Zi-Jiang

2014-11-01

Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. © The Author(s) 2014.

[Analysis of gene mutation of early onset epileptic spasm with unknown reason].

PubMed

Yang, X; Pan, G; Li, W H; Zhang, L M; Wu, B B; Wang, H J; Zhang, P; Zhou, S Z

2017-11-02

Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks

Early-onset scoliosis: current treatment.

PubMed

Cunin, V

2015-02-01

Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with

A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1.

PubMed

Li, Wei; Li, Jianhua; Ashok, Mala; Wu, Rongqian; Chen, Dazhi; Yang, Lihong; Yang, Huan; Tracey, Kevin J; Wang, Ping; Sama, Andrew E; Wang, Haichao

2007-03-15

The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., TNF, IL-1, and IFN-gamma) and late (e.g., high mobility group box 1 (HMGB1) protein) proinflammatory cytokines. The recent discovery of HMGB1 as a late mediator of lethal sepsis has prompted investigation for development of new experimental therapeutics. We found that many steroidal drugs (such as dexamethasone and cortisone) and nonsteroidal anti-inflammatory drugs (such as aspirin, ibuprofen, and indomethacin) failed to influence endotoxin-induced HMGB1 release even at superpharmacological concentrations (up to 10-25 microM). However, several steroid-like pigments (tanshinone I, tanshinone IIA, and cryptotanshinone) of a popular Chinese herb, Danshen (Salvia miltiorrhiza), dose dependently attenuated endotoxin-induced HMGB1 release in macrophage/monocyte cultures. A water-soluble tanshinone IIA sodium sulfonate derivative (TSNIIA-SS), which has been widely used as a Chinese medicine for patients with cardiovascular disorders, selectively abrogated endotoxin-induced HMGB1 cytoplasmic translocation and release in a glucocorticoid receptor-independent manner. Administration of TSNIIA-SS significantly protected mice against lethal endotoxemia and rescued mice from lethal sepsis even when the first dose was given 24 h after the onset of sepsis. The therapeutic effects were partly attributable to attenuation of systemic accumulation of HMGB1 (but not TNF and NO) and improvement of cardiovascular physiologic parameters (e.g., decrease in total peripheral vascular resistance and increase in cardiac stroke volume) in septic animals. Taken together, these data re-enforce the pathogenic role of HMGB1 in lethal sepsis, and support a therapeutic potential for TSNIIA-SS in the treatment of human sepsis.

A Cardiovascular Drug Rescues Mice from Lethal Sepsis by Selectively Attenuating a Late-Acting Proinflammatory Mediator, High Mobility Group Box 11

PubMed Central

Li, Wei; Li, Jianhua; Ashok, Mala; Wu, Rongqian; Chen, Dazhi; Yang, Lihong; Yang, Huan; Tracey, Kevin J.; Wang, Ping; Sama, Andrew E.; Wang, Haichao

2007-01-01

The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., TNF, IL-1, and IFN-γ) and late (e.g., high mobility group box 1 (HMGB1) protein) proinflammatory cytokines. The recent discovery of HMGB1 as a late mediator of lethal sepsis has prompted investigation for development of new experimental therapeutics. We found that many steroidal drugs (such as dexamethasone and cortisone) and nonsteroidal anti-inflammatory drugs (such as aspirin, ibuprofen, and indomethacin) failed to influence endotoxin-induced HMGB1 release even at superpharmacological concentrations (up to 10–25 μM). However, several steroid-like pigments (tanshinone I, tanshinone IIA, and cryptotanshinone) of a popular Chinese herb, Danshen (Salvia miltiorrhiza), dose dependently attenuated endotoxin-induced HMGB1 release in macrophage/monocyte cultures. A water-soluble tanshinone IIA sodium sulfonate derivative (TSNIIA-SS), which has been widely used as a Chinese medicine for patients with cardiovascular disorders, selectively abrogated endotoxin-induced HMGB1 cytoplasmic translocation and release in a glucocorticoid receptor-independent manner. Administration of TSNIIA-SS significantly protected mice against lethal endotoxemia and rescued mice from lethal sepsis even when the first dose was given 24 h after the onset of sepsis. The therapeutic effects were partly attributable to attenuation of systemic accumulation of HMGB1 (but not TNF and NO) and improvement of cardiovascular physiologic parameters (e.g., decrease in total peripheral vascular resistance and increase in cardiac stroke volume) in septic animals. Taken together, these data re-enforce the pathogenic role of HMGB1 in lethal sepsis, and support a therapeutic potential for TSNIIA-SS in the treatment of human sepsis. PMID:17339485

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

PubMed

Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

2016-12-01

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms.

PubMed

Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin; Black, Kathleen; Fernandez, Maria Victoria; Budde, John; Ibanez, Laura; Deming, Yuetiva; Kapoor, Manav; Tosto, Giuseppe; Mayeux, Richard P; Holtzman, David M; Fagan, Anne M; Morris, John C; Bateman, Randall J; Goate, Alison M; Harari, Oscar

2018-02-01

To determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD). Polygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk. We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. The highest association of the PRS and risk (odds ratio [OR] = 2.27; P = 1.29 × 10 -7 ) was observed in sEOAD, followed by fLOAD (OR = 1.75; P = 1.12 × 10 -7 ) and sLOAD (OR = 1.40; P = 1.21 × 10 -3 ). The PRS was associated with cerebrospinal fluid ptau 181 -Aβ 42 on eADAD (P = 4.36 × 10 -2 ). Our analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Interprofessional Collaboration to Improve Sepsis Care and Survival Within a Tertiary Care Emergency Department.

PubMed

Tedesco, Elizabeth R; Whiteman, Kimberly; Heuston, Melanie; Swanson-Biearman, Brenda; Stephens, Kimberly

2017-11-01

Sepsis is a leading cause of death in the United States; however, health care providers struggle with timely recognition, diagnosis, and treatment of patients. Both the Centers for Medicare and Medicaid Services and the National Quality Forum have identified this diagnosis as a priority. Presently, many patients with sepsis are identified late, resulting in significant morbidity and death. In this project, a collaborative, interprofessional approach was created for screening and early identification of ED patients with possible sepsis. The department has 38 beds with annual patient volumes of more than 40,000 visits. Education was provided about the symptoms and treatment of patients with sepsis. A screening and management algorithm tool was instituted that consisted of early identification triggers and how to intervene according to Surviving Sepsis Campaign recommendations. The tool allowed for assessment of the patient by the ED team; the team worked to determine if sepsis was present and the extent of the illness. During the first 4 months after implementation, more than 240 patients were screened, assessed, and treated according to the algorithm. Project outcomes resulted in an increase in staff knowledge of sepsis, a decrease in length of stay by 3 hours, and a significant decrease in mortality when compared with the previous year's coded data. This project demonstrates that sepsis education and team collaboration are an integral part of identifying and treating patients with sepsis. An interprofessional collaborative approach could be implemented in other institutions to combat the life-threatening complications of sepsis. Copyright © 2017 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

Anaesthetic management of patients with severe sepsis.

PubMed

Eissa, D; Carton, E G; Buggy, D J

2010-12-01

Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

Deferred and immediate imitation in regressive and early onset autism

PubMed Central

Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

2010-01-01

Deferred imitation has long held a privileged position in early cognitive development, considered an early marker of representational thought with links to language development and symbolic processes. Children with autism have difficulties with several abilities generally thought to be related to deferred imitation: immediate imitation, language, and symbolic play. However, few studies have examined deferred imitation in early autism. The present study examined both deferred, spontaneous imitation and immediate, elicited imitation on a set of carefully matched tasks in 36 young children with autism: 16 with early onset autism, 20 with regressive autism and two contrast groups, younger typically developing children (n = 20) and age matched children with significant developmental delays (n = 21). Analyses of co-variance controlling for differences in verbal mental age revealed significant main effects for task, but no main effect of group and no interaction of task by group. Deferred imitation scores were lower than immediate imitation scores for all groups. Imitation performance was related to overall intellectual functioning for all groups, and there were moderate and significant relations between imitation in the immediate elicited condition and in the spontaneous deferred condition for all groups. Finally, there were no differences between onset subgroups in imitation scores, suggesting that the two share a similar phenotype involving both types of imitation. PMID:18221343

First impression at stroke onset plays an important role in early hospital arrival.

PubMed

Iguchi, Yasuyuki; Wada, Kuniyasu; Shibazaki, Kensaku; Inoue, Takeshi; Ueno, Yuji; Yamashita, Shinji; Kimura, Kazumi

2006-01-01

Treatment for acute ischemic stroke should be administered as soon as possible after symptom onset. The aim of this study was to investigate whether or not the patient's and bystander's first impression at stroke onset was associated with hospital arrival time. To investigate the factors influencing the prehospital delay, we prospectively interviewed consecutive stroke patients and bystanders about their first impression at the stroke onset and assessed the methods of transportation, and clinical characteristics. Early arrival was defined as a hospital arrival of within 2 h from stroke onset. One hundred thirty patients were enrolled: 82% were ischemic stroke and 18% were cerebral hemorrhage. The median interval between symptom onset and the hospital arrival was 7.5 h and 30% of patients presented within 2 h of stroke onset. First impression of stroke (odds ratios [OR] 4.56, 95% confidence interval [CI] 1.54-13.5, p=0.006), presence of consciousness disturbance (OR 4.29, CI 1.39-13.3, p=0.011), arrival through other facilities (OR 0.25, CI 0.08-0.76, p=0.015), a history of diabetes (OR 0.23, CI 0.06-0.80, p=0.028) and nocturnal onset (OR 0.19, CI 0.04-0.88, p=0.042) independently contributed to the early arrival. The first impression of patients and bystanders at stroke onset is important in order to reach hospital earlier in Japan. Public educational systems such as those, which advertise stroke warning signs, are necessary.

Heterogeneous models for an early discrimination between sepsis and non-infective SIRS in medical ward patients: a pilot study.

PubMed

Mearelli, Filippo; Fiotti, Nicola; Altamura, Nicola; Zanetti, Michela; Fernandes, Giovanni; Burekovic, Ismet; Occhipinti, Alessandro; Orso, Daniele; Giansante, Carlo; Casarsa, Chiara; Biolo, Gianni

2014-10-01

The objective of the study was to determine the accuracy of phospholipase A2 group II (PLA2-II), interferon-gamma-inducible protein 10 (IP-10), angiopoietin-2 (Ang-2), and procalcitonin (PCT) plasma levels in early ruling in/out of sepsis among systemic inflammatory response syndrome (SIRS) patients. Biomarker levels were determined in 80 SIRS patients during the first 4 h of admission to the medical ward. The final diagnosis of sepsis or non-infective SIRS was issued according to good clinical practice. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for sepsis diagnosis were assessed. The optimal biomarker combinations with clinical variables were investigated by logistic regression and decision tree (CART). PLA2-II, IP-10 and PCT, but not Ang-2, were significantly higher in septic (n = 60) than in non-infective SIRS (n = 20) patients (P ≤ 0.001, 0.027, and 0.002, respectively). PLA2-II PPV and NPV were 88 and 86%, respectively. The corresponding figures were 100 and 31% for IP-10, and 93 and 35% for PCT. Binary logistic regression model had 100% PPV and NPV, while manual and software-generated CART reached an overall accuracy of 95 and 98%, respectively, both with 100% NPV. PLA2-II and IP-10 associated with clinical variables in regression or decision tree heterogeneous models may be valuable biomarkers for sepsis diagnosis in SIRS patients admitted to medical ward (MW). Further studies are needed to introduce them into clinical practice.

Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

PubMed

Kang, Cheol-In; Song, Jae-Hoon; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Yeom, Joon-Sup; Ki, Hyun Kyun; Son, Jun Seong; Lee, Seung Soon; Kim, Yeon-Sook; Jung, Sook-In; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Hyuck; Moon, Chisook

2011-01-01

The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

PubMed

Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

2018-04-01

Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Early onset marfan syndrome: Atypical clinical presentation of two cases

PubMed Central

Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

2015-01-01

Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

Early-onset Major Depressive Disorder in men is associated with childlessness.

PubMed

Yates, William R; Meller, William H; Lund, Brian C; Thurber, Steve; Grambsch, Patricia L

2010-07-01

The self-reported number of children was compared for men and women from the National Epidemiologic Survey of Alcoholism and Related Conditions Survey (NESARC). Subjects with a diagnosis of major depressive disorder or bipolar disorder were compared to those without an axis I disorder. The effect of age, gender, marriage and diagnostic status on number of children was completed using multivariate analyses. Men with a history of major depressive disorder but not bipolar disorder reported higher rates of childlessness and lower mean number of children. This reduced number of children was related to an early age of onset of MDD. Thirty percent of men with an age of onset of MDD before 22 were childless compared to only 18.9% of men without an axis I disorder (Odds ratio=1.82, 95% CI=1.45-2.27). No effect of mood disorder on number of children was found in women with major depression or bipolar disorder. This study suggests that an early age of onset of major depressive disorder contributes to childlessness in men.

Functional Connectivity of the Amygdala in Early Childhood Onset Depression

PubMed Central

Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

2011-01-01

Objective Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early childhood onset MDD. Method Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777

Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy

PubMed Central

Nair, Umesh; Malhotra, Sony; Meyer, Esther; Trump, Natalie; Gazina, Elena V.; Papandreou, Apostolos; Ngoh, Adeline; Ackermann, Sally; Ambegaonkar, Gautam; Appleton, Richard; Desurkar, Archana; Eltze, Christin; Kneen, Rachel; Kumar, Ajith V.; Lascelles, Karine; Montgomery, Tara; Ramesh, Venkateswaran; Samanta, Rajib; Scott, Richard H.; Tan, Jeen; Whitehouse, William; Poduri, Annapurna; Scheffer, Ingrid E.; Chong, W.K. “Kling”; Cross, J. Helen; Topf, Maya; Petrou, Steven

2018-01-01

Objective To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset KCNT1 epilepsy. Methods We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified KCNT1 variants on local diagnostic multiple gene panel testing were also included. When possible, we performed homology modeling to predict the putative effects of variants on protein structure and function. We undertook electrophysiologic assessment of mutant KCNT1 channels in a xenopus oocyte model system. Results We identified pathogenic variants in KCNT1 in 12 patients, 4 of which are novel. Most variants occurred de novo. Ten patients had a clinical diagnosis of EIMFS, and the other 2 presented with early-onset severe nocturnal frontal lobe seizures. Three patients had a trial of quinidine with good clinical response in 1 patient. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. Conclusions Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Currently, genotype-phenotype correlations are unclear, although clinical outcome is poor for the majority of cases. Further elucidation of disease mechanisms may facilitate the development of targeted treatments, much needed for this pharmacoresistant genetic epilepsy. PMID:29196579

Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit.

PubMed

Sakr, Yasser; Rubatto Birri, Paolo Nahuel; Kotfis, Katarzyna; Nanchal, Rahul; Shah, Bhagyesh; Kluge, Stefan; Schroeder, Mary E; Marshall, John C; Vincent, Jean-Louis

2017-03-01

Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. Observational cohort study. Seven hundred and thirty ICUs in 84 countries. All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.

Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

ERIC Educational Resources Information Center

Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

2016-01-01

This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

Sepsis-induced morbidity in mice: effects on body temperature, body weight, cage activity, social behavior and cytokines in brain

PubMed Central

Granger, Jill I.; Ratti, Pietro-Luca; Datta, Subhash C.; Raymond, Richard M.; Opp, Mark R.

2012-01-01

Infection negatively impacts mental health, as evidenced by the lethargy, malaise, and cognitive deficits experienced during illness. These changes in central nervous system processes, collectively termed sickness behavior, have been shown in animal models to be mediated primarily by the actions of cytokines in brain. Most studies of sickness behavior to date have used bolus injection of bacterial lipopolysaccharide (LPS) or selective administration of the proinflammatory cytokines interleukin-1β (IL-1β) or IL-6 as the immune challenge. Such models, although useful for determining mechanisms responsible for acute changes in physiology and behavior, do not adequately represent the more complex effects on central nervous system (CNS) processes of a true infection with replicating pathogens. In the present study, we used the cecal ligation and puncture (CLP) model to quantify sepsis-induced alterations in several facets of physiology and behavior of mice. We determined the impact of sepsis on cage activity, body temperature, food and water consumption and body weights of mice. Because cytokines are critical mediators of changes in behavior and temperature regulation during immune challenge, we also quantified sepsis-induced alterations in cytokine mRNA and protein in brain during the acute period of sepsis onset. We now report that cage activity and temperature regulation in mice that survive are altered for up to 23 days after sepsis induction. Food and water consumption are transiently reduced, and body weight is lost during sepsis. Furthermore, sepsis decreases social interactions for 24 – 48 hours. Finally, mRNA and protein for IL-1β, IL-6, and tumor necrosis factor-α (TNFα) are upregulated in the hypothalamus, hippocampus, and brain stem during sepsis onset, from 6–72 hour post sepsis induction. Collectively, these data indicate that sepsis not only acutely alters physiology, behavior and cytokine profiles in brain, but that some brain functions are

Epidemiologic features, risk factors, and outcome of sepsis in stroke patients treated on a neurologic intensive care unit.

PubMed

Berger, Benjamin; Gumbinger, Christoph; Steiner, Thorsten; Sykora, Marek

2014-04-01

Because of the immune-suppressive effect of cerebral damage, stroke patients are at high risk for infections. These might result in sepsis, which is the major contributor to intensive care unit (ICU) mortality. Although there are numerous studies on infections in stroke patients, the role of sepsis as a poststroke complication is unknown. We retrospectively analyzed incidence of and risk factors for sepsis acquisition as well as outcome parameters of 238 patients with ischemic or hemorrhagic strokes consecutively admitted to the neurologic ICU in a tertiary university hospital between January 1, 2009, and December 31, 2010. Basic demographic and clinical data including microbiological parameters as well as factors describing stroke severity (eg, lesion volume and National Institute of Health stroke scale score) were recorded and included into the analysis. The diagnosis of sepsis was based on the criteria of the German Sepsis Society. We identified 30 patients (12.6%) with sepsis within the first 7 days from stroke onset. The lungs were the most frequent source of infection (93.3%), and gram-positive organisms were dominating the microbiologic spectrum (52.4%). Comorbidities (chronic obstructive pulmonary disease and immunosuppressive disorders) and Simplified Acute Physiology Score II but none of the factors describing stroke severity were independent predictors of sepsis acquisition. Sepsis was associated with a significantly worse prognosis, leading to a 2-fold increased mortality rate during in-hospital care (36.7% vs 18.8%) and after 3 months (56.5% vs 28.5%), but only in the subgroup of supratentorial hemorrhages, it was an independent predictor of in-hospital and 3-month mortality. Other factors significantly associated with death in a multivariate analysis were chronic obstructive pulmonary disease, malignancies (in-hospital mortality only), and Simplified Acute Physiology Score II (3-month mortality only) for ischemia and heart failure (in

Importance of measuring lactate levels in children with sepsis.

PubMed

Anil, Nisha

2017-10-10

Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

PubMed Central

2010-01-01

Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01). Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock. PMID:20181046

Ghrelin clearance is reduced at the late stage of polymicrobial sepsis.

PubMed

Wu, Rongqian; Zhou, Mian; Cui, Xiaoxuan; Simms, H Hank; Wang, Ping

2003-11-01

The cardiovascular response to sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Ghrelin, a newly-identified endogenous ligand for growth hormone secretagogue receptor (i.e., ghrelin receptor), was recently demonstrated to be a potent vasoactive peptide in addition to its effects on growth hormone release and energy homeostasis. We have shown that ghrelin (via its receptor) may play an important role in regulating cardiovascular responses in the progression of polymicrobial sepsis. However, it remains unknown whether the clearance of this peptide is altered in sepsis. To determine this, male adult rats were injected with 125I-ghrelin through the jugular vein at 5 or 20 h after cecal ligation and puncture (CLP, i.e., sepsis model) or sham operation. The blood sample was collected every 2 min for 30 min for determining half-life (t1/2). Tissue samples (i.e., kidneys, liver, brain, heart, lungs, spleen, stomach, small intestine, large intestine, skin and muscle) were then harvested. The radioactivities of samples were counted. The results indicate that 125I-ghrelin's t1/2 and its distribution were not significantly altered in early sepsis (5 h after CLP). However, the t1/2 increased significantly in late sepsis (20 h after CLP). Tissue distribution of 125I-ghrelin was far greater in the kidneys than in any other tissues tested in both sham and septic animals. Moreover, the kidneys and liver had significantly less radioactive uptake at 20 h after CLP, but the radioactivity in blood was much higher at the same time point. There were no significant changes in 125I-ghrelin distribution in other organs at the late stage of sepsis. These results indicate that the kidneys are the primary site of ghrelin clearance, which is significantly diminished in late sepsis. In addition, the liver also plays a role in the clearance of ghrelin, which was also reduced in late sepsis. The decreased clearance of ghrelin by the kidneys and liver

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department.

PubMed

Viale, Pierluigi; Tedeschi, Sara; Scudeller, Luigia; Attard, Luciano; Badia, Lorenzo; Bartoletti, Michele; Cascavilla, Alessandra; Cristini, Francesco; Dentale, Nicola; Fasulo, Giovanni; Legnani, Giorgio; Trapani, Filippo; Tumietto, Fabio; Verucchi, Gabriella; Virgili, Giulio; Berlingeri, Andrea; Ambretti, Simone; De Molo, Chiara; Brizi, Mara; Cavazza, Mario; Giannella, Maddalena

2017-10-15

The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

[The relationship between accommodative accuracy at different near-work distances and early-onset myopia].

PubMed

Yu, Q W; Zhang, P; Zhou, S B; Hu, Y; Ji, M X; Luo, Y C; You, H L; Yao, Z X

2016-07-01

To observe the accommodative accuracy of children with early-onset myopia at different near-work distances, and discuss the relationship between accommodative accuracy and early-onset myopia. This was a case-control study. Thirty-seven emmetropic children, 41 early-onset myopic children without correction, and 39 early-onset myopic children with spectacles, aged 7 to 13 years, were included. Measures of refractive errors and accommodative accuracy at four near-work distances, including 50 cm, 40 cm, 30 cm, and 20 cm, were made using the binocular fusion cross cylinder (FCC) of an automatic phoropter. Most candidates showed accommodative lags, including the children with emmetropia. The ratio of lags in all candidates at different near-work distances was 75.21% (50 cm), 87.18% (40 cm), 92.31% (30 cm), and 98.29% (20 cm), respectively. All accommodative accuracies became worse, and the accommodative lag ratio and values of FCC increased, along with the shortening of the distance. The difference in accommodative accuracy among groups was statistically significant at 30 cm (χ(2)=7.852, P= 0.020) and 20 cm (χ(2)=6.480, P=0.039). The values of FCC among groups were significantly different at 30 cm (F=3.626, P=0.030) and 20 cm (F=3.703, P=0.028), but not at 50 cm and 40 cm (P>0.05). In addition, the FCC values of 30 cm and 20 cm had a statistically significant difference between myopic children without correction [(1.25±0.44) D and (1.76±0.43) D] and emmetropic children [(0.95±0.52) D and (1.41±0.58) D] (P=0.012, 0.008). The correlation between diopters of myopia and accommodative accuracy at different nearwork distances was not statistically significant (P>0.05). However, the correlation between diopters of myopia and the accommodative lag value (FCC) at 20 cm was statistically significant (r=0.246, P=0.028). The closer the near-work distance is, the worse the accommodative accuracy is. This is more significant in early-onset myopia, especially myopia without

Integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes.

PubMed

Langley, Raymond J; Tipper, Jennifer L; Bruse, Shannon; Baron, Rebecca M; Tsalik, Ephraim L; Huntley, James; Rogers, Angela J; Jaramillo, Richard J; O'Donnell, Denise; Mega, William M; Keaton, Mignon; Kensicki, Elizabeth; Gazourian, Lee; Fredenburgh, Laura E; Massaro, Anthony F; Otero, Ronny M; Fowler, Vance G; Rivers, Emanuel P; Woods, Chris W; Kingsmore, Stephen F; Sopori, Mohan L; Perrella, Mark A; Choi, Augustine M K; Harrod, Kevin S

2014-08-15

Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel molecular signature of clinical sepsis. To develop a biomarker panel to characterize sepsis in primates and ascertain its relevance to early diagnosis and progression of human sepsis. Intravenous inoculation of Macaca fascicularis with Escherichia coli produced mild to severe sepsis, lung injury, and death. Plasma samples were obtained before and after 1, 3, and 5 days of E. coli challenge and at the time of killing. At necropsy, blood, lung, kidney, and spleen samples were collected. An integrative analysis of the metabolomic and transcriptomic datasets was performed to identify a panel of sepsis biomarkers. The extent of E. coli invasion, respiratory distress, lethargy, and mortality was dependent on the bacterial dose. Metabolomic and transcriptomic changes characterized severe infections and death, and indicated impaired mitochondrial, peroxisomal, and liver functions. Analysis of the pulmonary transcriptome and plasma metabolome suggested impaired fatty acid catabolism regulated by peroxisome-proliferator activated receptor signaling. A representative four-metabolite model effectively diagnosed sepsis in primates (area under the curve, 0.966) and in two human sepsis cohorts (area under the curve, 0.78 and 0.82). A model of sepsis based on reciprocal metabolomic and transcriptomic data was developed in primates and validated in two human patient cohorts. It is anticipated that the identified parameters will facilitate early diagnosis and management of sepsis.

Sepsis biomarkers.

PubMed

Prucha, Miroslav; Bellingan, Geoff; Zazula, Roman

2015-02-02

Sepsis is the most frequent cause of death in non-coronary intensive care units (ICUs). In the past 10 years, progress has been made in the early identification of septic patients and in their treatment and these improvements in support and therapy mean that the mortality is gradually decreasing but it still remains unacceptably high. Leaving clinical diagnosis aside, the laboratory diagnostics represent a complex range of investigations that can place significant demands on the system given the speed of response required. There are hundreds of biomarkers which could be potentially used for diagnosis and prognosis in septic patients. The main attributes of successful markers would be high sensitivity, specificity, possibility of bed-side monitoring, and financial accessibility. Only a fraction is used in routine clinical practice because many lack sufficient sensitivity or specificity. The following review gives a short overview of the current epidemiology of sepsis, its pathogenesis and state-of-the-art knowledge on the use of specific biochemical, hematological and immunological parameters in its diagnostics. Prospective approaches towards discovery of new diagnostic biomarkers have been shortly mentioned. Copyright © 2014 Elsevier B.V. All rights reserved.

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

PubMed Central

Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

2011-01-01

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

Surveillance plan for the early detection of H5N1 highly pathogenic avian influenza virus in migratory birds in the United States: surveillance year 2009

USGS Publications Warehouse

Brand, Christopher J.

2009-01-01

Executive Summary: This Surveillance Plan (Plan) describes plans for conducting surveillance of wild birds in the United States and its Territories and Freely-Associated States to provide for early detection of the introduction of the H5N1 Highly Pathogenic Avian Influenza (HPAI) subtype of the influenza A virus by migratory birds during the 2009 surveillance year, spanning the period of April 1, 2009 - March 31, 2010. The Plan represents a continuation of surveillance efforts begun in 2006 under the Interagency Strategic Plan for the Early Detection of H5N1 Highly Pathogenic Avian Influenza in Wild Migratory Birds (U.S. Department of Agriculture and U.S. Department of the Interior, 2006). The Plan sets forth sampling plans by: region, target species or species groups to be sampled, locations of sampling, sample sizes, and sampling approaches and methods. This Plan will be reviewed annually and modified as appropriate for subsequent surveillance years based on evaluation of information from previous years of surveillance, changing patterns and threats of H5N1 HPAI, and changes in funding availability for avian influenza surveillance. Specific sampling strategies will be developed accordingly within each of six regions, defined here as Alaska, Hawaiian/Pacific Islands, Lower Pacific Flyway (Washington, Oregon, California, Idaho, Nevada, Arizona), Central Flyway, Mississippi Flyway, and Atlantic Flyway.

Staphylococcus aureus Sepsis Induces Early Renal Mitochondrial DNA Repair and Mitochondrial Biogenesis in Mice

PubMed Central

Bartz, Raquel R.; Fu, Ping; Suliman, Hagir B.; Crowley, Stephen D.; MacGarvey, Nancy Chou; Welty-Wolf, Karen; Piantadosi, Claude A.

2014-01-01

Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control), 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection. PMID:24988481

Clinical Characteristics and Outcomes of Sepsis-Related vs Non-Sepsis-Related ARDS

PubMed Central

Sheu, Chau-Chyun; Gong, Michelle N.; Zhai, Rihong; Chen, Feng; Bajwa, Ednan K.; Clardy, Peter F.; Gallagher, Diana C.; Thompson, B. Taylor

2010-01-01

Background: ARDS may occur after either septic or nonseptic injuries. Sepsis is the major cause of ARDS, but little is known about the differences between sepsis-related and non-sepsis-related ARDS. Methods: A total of 2,786 patients with ARDS-predisposing conditions were enrolled consecutively into a prospective cohort, of which 736 patients developed ARDS. We defined sepsis-related ARDS as ARDS developing in patients with sepsis and non-sepsis-related ARDS as ARDS developing after nonseptic injuries, such as trauma, aspiration, and multiple transfusions. Patients with both septic and nonseptic risks were excluded from analysis. Results: Compared with patients with non-sepsis-related ARDS (n = 62), patients with sepsis-related ARDS (n = 524) were more likely to be women and to have diabetes, less likely to have preceding surgery, and had longer pre-ICU hospital stays and higher APACHE III (Acute Physiology and Chronic Health Evaluation III) scores (median, 78 vs 65, P < .0001). There were no differences in lung injury score, blood pH, Pao2/Fio2 ratio, and Paco2 on ARDS diagnosis. However, patients with sepsis-related ARDS had significantly lower Pao2/Fio2 ratios than patients with non-sepsis-related ARDS patients on ARDS day 3 (P = .018), day 7 (P = .004), and day 14 (P = .004) (repeated-measures analysis, P = .011). Compared with patients with non-sepsis-related ARDS, those with sepsis-related had a higher 60-day mortality (38.2% vs 22.6%; P = .016), a lower successful extubation rate (53.6% vs 72.6%; P = .005), and fewer ICU-free days (P = .0001) and ventilator-free days (P = .003). In multivariate analysis, age, APACHE III score, liver cirrhosis, metastatic cancer, admission serum bilirubin and glucose levels, and treatment with activated protein C were independently associated with 60-day ARDS mortality. After adjustment, sepsis-related ARDS was no longer associated with higher 60-day mortality (hazard ratio, 1.26; 95% CI, 0.71-2.22). Conclusion: Sepsis