Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

PubMed Central

Kasperavičiūtė, Dalia; Catarino, Claudia B.; Matarin, Mar; Leu, Costin; Novy, Jan; Tostevin, Anna; Leal, Bárbara; Hessel, Ellen V. S.; Hallmann, Kerstin; Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Ryten, Mina; Trabzuni, Daniah; Ramasamy, Adaikalavan; Alhusaini, Saud; Doherty, Colin P.; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J.; Zumsteg, Dominik; Duncan, Susan; Kälviäinen, Reetta K.; Eriksson, Kai J.; Kantanen, Anne-Mari; Pandolfo, Massimo; Gruber-Sedlmayr, Ursula; Schlachter, Kurt; Reinthaler, Eva M.; Stogmann, Elisabeth; Zimprich, Fritz; Théâtre, Emilie; Smith, Colin; O’Brien, Terence J.; Meng Tan, K.; Petrovski, Slave; Robbiano, Angela; Paravidino, Roberta; Zara, Federico; Striano, Pasquale; Sperling, Michael R.; Buono, Russell J.; Hakonarson, Hakon; Chaves, João; Costa, Paulo P.; Silva, Berta M.; da Silva, António M.; de Graan, Pierre N. E.; Koeleman, Bobby P. C.; Becker, Albert; Schoch, Susanne; von Lehe, Marec; Reif, Philipp S.; Rosenow, Felix; Becker, Felicitas; Weber, Yvonne; Lerche, Holger; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo M.; Kobow, Katja; Coras, Roland; Blumcke, Ingmar; Scheffer, Ingrid E.; Berkovic, Samuel F.; Weale, Michael E.; Delanty, Norman; Depondt, Chantal; Cavalleri, Gianpiero L.; Kunz, Wolfram S.

2013-01-01

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26–1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures. PMID:24014518

Colony-stimulating factor use and impact on febrile neutropenia among patients with newly diagnosed breast, colorectal, or non-small cell lung cancer who were receiving chemotherapy.

PubMed

McCune, Jeannine S; Sullivan, Sean D; Blough, David K; Clarke, Lauren; McDermott, Cara; Malin, Jennifer; Ramsey, Scott

2012-01-01

To determine the impact of primary prophylactic colony-stimulating factor (CSF) use on febrile neutropenia in a large patient population receiving contemporary chemotherapy regimens to treat breast cancer, colorectal cancer, or non-small cell lung cancer (NSCLC). Retrospective claims analysis. The Surveillance, Epidemiology, and End Results (SEER)-Puget Sound cancer registry and insurance claims records. A total of 2728 patients aged 25 years or older who received a diagnosis of breast cancer (998 patients), colorectal cancer (688 patients), or NSCLC (1042 patients) between January 1, 2002, and December 31, 2005, and received chemotherapy. Initial chemotherapy regimen, CSF use (filgrastim or pegfilgrastim), and febrile neutropenia events were evaluated after the first chemotherapy administration. Subsequently, febrile neutropenia rates in patients receiving primary prophylactic CSF were compared with febrile neutropenia rates in patients receiving CSF in settings other than primary prophylaxis or not at all. The impact of primary prophylactic CSF could not be assessed for patients with colorectal cancer or NSCLC because only 1 and 18 febrile neutropenia events, respectively, occurred in those receiving primary prophylactic CSF. Of the 998 patients with breast cancer, 72 (7.2%) experienced febrile neutropenia, 28 of whom received primary prophylactic CSF. In the patients with breast cancer, we observed that primary prophylactic CSF use was associated with reduced febrile neutropenia rates; however, the analysis may have been confounded by unmeasured factors associated with febrile neutropenia. The impact of primary prophylactic CSFs on febrile neutropenia rates could not be demonstrated. Given the substantive cost of CSFs to pharmacy budgets, there are numerous opportunities for pharmacists to optimize CSF use. Research studies are needed to evaluate if guideline-directed prescribing of primary prophylactic CSFs can improve clinical outcomes. © 2012 Pharmacotherapy Publications, Inc.

Early discontinuation of antibiotic prophylaxis in patients with persistent primary vesicoureteral reflux initially detected during infancy: outcome analysis and risk factors for febrile urinary tract infection.

PubMed

Moriya, Kimihiko; Mitsui, Takahiko; Kitta, Takeya; Nakamura, Michiko; Kanno, Yukiko; Kon, Masafumi; Nishimura, Yoko; Shinohara, Nobuo; Nonomura, Katsuya

2015-02-01

We retrospectively assessed the incidence of and risk factors for febrile urinary tract infection in children during active surveillance after early discontinuation of antibiotic prophylaxis. We retrospectively evaluated 9 females and 61 uncircumcised males diagnosed with primary vesicoureteral reflux before age 1 year who had persistent reflux on followup voiding cystourethrogram and were subsequently followed under active surveillance without continuous antibiotic prophylaxis. Patients with secondary vesicoureteral reflux or associated urological abnormality were excluded. Clinical outcomes, including incidence of febrile urinary tract infection and new scar formation, were evaluated. Risk factors for febrile urinary tract infection were also analyzed. Mean age at stopping continuous antibiotic prophylaxis was 21 months, and mean followup was 61 months. During active surveillance 21 patients had febrile urinary tract infection, and the 5-year infection-free rate under active surveillance was 67.5%. One or 2 foci of minimal new scarring developed in 4 of 16 patients who underwent followup dimercapto-succinic acid scan after febrile urinary tract infection. On multivariate analysis dilated vesicoureteral reflux on followup voiding cystourethrogram was the only significant risk factor for febrile urinary tract infection. This study revealed that about two-thirds of patients with persistent vesicoureteral reflux were free of febrile urinary tract infection during 5 years of active surveillance. Those with dilated vesicoureteral reflux on followup voiding cystourethrogram are at significantly greater risk for febrile urinary tract infection. Accordingly active surveillance, especially in patients with nondilated vesicoureteral reflux on followup voiding cystourethrogram, seems to be a safe option even in children who have not yet been toilet trained. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Quantitative Evaluation of Medial Temporal Lobe Morphology in Children with Febrile Status Epilepticus: Results of the FEBSTAT Study.

PubMed

McClelland, A C; Gomes, W A; Shinnar, S; Hesdorffer, D C; Bagiella, E; Lewis, D V; Bello, J A; Chan, S; MacFall, J; Chen, M; Pellock, J M; Nordli, D R; Frank, L M; Moshé, S L; Shinnar, R C; Sun, S

2016-12-01

The pathogenesis of febrile status epilepticus is poorly understood, but prior studies have suggested an association with temporal lobe abnormalities, including hippocampal malrotation. We used a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus. Brain MR imaging was performed in children presenting with febrile status epilepticus and control subjects as part of the Consequences of Prolonged Febrile Seizures in Childhood study. Medial temporal lobe morphologic parameters were measured manually, including the distance of the hippocampus from the midline, hippocampal height:width ratio, hippocampal angle, collateral sulcus angle, and width of the temporal horn. Temporal lobe morphologic parameters were correlated with the presence of visual hippocampal malrotation; the strongest association was with left temporal horn width (P < .001; adjusted OR, 10.59). Multiple morphologic parameters correlated with febrile status epilepticus, encompassing both the right and left sides. This association was statistically strongest in the right temporal lobe, whereas hippocampal malrotation was almost exclusively left-sided in this cohort. The association between temporal lobe measurements and febrile status epilepticus persisted when the analysis was restricted to cases with visually normal imaging findings without hippocampal malrotation or other visually apparent abnormalities. Several component morphologic features of hippocampal malrotation are independently associated with febrile status epilepticus, even when complete hippocampal malrotation is absent. Unexpectedly, this association predominantly involves the right temporal lobe. These findings suggest that a spectrum of bilateral temporal lobe anomalies are associated with febrile status epilepticus in children. Hippocampal malrotation may represent a visually apparent subset of this spectrum. © 2016 by American Journal of Neuroradiology.

Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan-Induced Febrile Neutropenia

PubMed Central

de Jong, Floris A.; van Schaik, Ron H.; Sparreboom, Alex; van Fessem, Marianne A.; van de Geijn, Fleur E.; van Daele, Paul L.; Verweij, Jaap; Sleijfer, Stefan; Mathijssen, Ron H.

2010-01-01

Objective. Mannose-binding lectin (MBL) is important in the innate immune response. MBL2 gene polymorphisms affect MBL expression, and genotypes yielding low MBL levels have been associated with an elevated risk for infections in hematological cancer patients undergoing chemotherapy. However, these reported associations are inconsistent, and data on patients with solid tumors are lacking. Here, we investigated the effects of MBL2 genotypes on irinotecan-induced febrile neutropenia in patients with solid tumors. Patients and Methods. Irinotecan-treated patients were genotyped for the MBL2 gene. Two promoter (−550 H/L and −221 X/Y) and three exon polymorphisms (52 A/D, 54 A/B, and 57 A/C) were determined, together with known risk factors for irinotecan-induced toxicity. Neutropenia and febrile neutropenia were recorded during the first course. Results. Of the 133 patients, 28% experienced severe neutropenia and 10% experienced febrile neutropenia. No associations were found between exon polymorphisms and febrile neutropenia. However, patients with the H/H promoter genotype, associated with high MBL levels, experienced significantly more febrile neutropenia than patients with the H/L and L/L genotypes (20% versus 13% versus 5%). Moreover, patients with the HYA haplotype encountered significantly more febrile neutropenia than patients without this high MBL-producing haplotype (16% versus 4%). In the subgroup with wild-type exon polymorphisms (A/A), patients with the high MBL promoter phenotype had the highest incidence of febrile neutropenia, regardless of known risk factors. Conclusion. Patients with high MBL2 promoter genotypes and haplotypes seem more at risk for developing febrile neutropenia. If confirmed, these preliminary findings may contribute to more individualized approaches of irinotecan treatment. PMID:20930093

Microorganisms isolated from cultures and infection focus and antibiotic treatments in febrile neutropenic children from Şanlıurfa, Turkey.

PubMed

Özdemir, Z Canan; Koç, Ahmet; Ayçiçek, Ali

2016-01-01

Chemotherapy induced febrile neutropenia predisposes patients to life threatening infections. We aimed to determine the causative microorganisms, infection focus and antibiotic treatment success in febrile neutropenic children with leukemia. A total of 136 febrile neutropenic episodes in 48 leukemic children were reviewed retrospectively from records. Among 136 febrile neutropenic episodes, 68 (50%) episodes were microbiologically documented. Methicillin sensitive coagulase (-) Staphylococcus aureus were the most common isolates from hemoculture (20.5%). The most frequently documented infection focus was mucositis (31.9%). Ceftazidime plus amikacin was the most commonly used antimicrobial treatment for the empirical therapy (52.9%). The overall response rates were 70.5%, 86.9%, and 66.6% of first line, second line and third line therapies, respectively. The spectrum of isolates among febrile neutropenic children in our hematology clinic appears to be gram positive pathogens which are the most common agents. Therefore the, documentation of the flora in each unit could help to decide appropriate empirical therapy which is life saving.

[A pilot study of antibiotic cycling for the treatment of febrile neutropenia patients with hematological diseases].

PubMed

Ikegaya, Satoshi; Iwasaki, Hiromichi; Kinoshita, Keiichi; Urasaki, Yoshimasa; Tsutani, Hiroshi; Ueda, Takanori

2004-03-01

Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times. The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period. There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period. However, the efficacy rate has been rising and febrile duration has been shortening by degrees. Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling. Recently, antibiotic cycling therapy has attracted attention especially in the ICU. However, a clinical study of treatment for febrile neutropenia has not been reported. Our trial suggests that cycling therapy may be useful for febrile neutropenia. However, Some deviation in the patients characteristics of each period may affect the result. It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia.

Bilateral hippocampal atrophy in temporal lobe epilepsy: Effect of depressive symptoms and febrile seizures

PubMed Central

Finegersh, Andrey; Avedissian, Christina; Shamim, Sadat; Dustin, Irene; Thompson, Paul M.; Theodore, William H.

2011-01-01

Summary Purpose Neuroimaging studies suggest a history of febrile seizures, and depression, are associated with hippocampal volume reductions in patients with temporal lobe epilepsy (TLE). Methods We used radial atrophy mapping (RAM), a three-dimensional (3D) surface modeling tool, to measure hippocampal atrophy in 40 patients with unilateral TLE, with or without a history of febrile seizures and symptoms of depression. Multiple linear regression was used to single out the effects of covariates on local atrophy. Key Findings Subjects with a history of febrile seizures (n = 15) had atrophy in regions corresponding to the CA1 and CA3 subfields of the hippocampus contralateral to seizure focus (CHC) compared to those without a history of febrile seizures (n = 25). Subjects with Beck Depression Inventory II (BDI-II) score ≥14 (n = 11) had atrophy in the superoanterior portion of the CHC compared to subjects with BDI-II <14 (n = 29). Significance Contralateral hippocampal atrophy in TLE may be related to febrile seizures or depression. PMID:21269286

The incidence and risk factors of febrile neutropenia in chemotherapy-naïve lung cancer patients receiving etoposide plus platinum.

PubMed

Fujiwara, Takumi; Kenmotsu, Hirotsugu; Naito, Tateaki; Kawamura, Takahisa; Mamesaya, Nobuaki; Kotake, Mie; Kobayashi, Haruki; Omori, Shota; Nakashima, Kazuhisa; Wakuda, Kazushige; Ono, Akira; Taira, Tetsuhiko; Murakami, Haruyasu; Omae, Katsuhiro; Mori, Keita; Endo, Masahiro; Takahashi, Toshiaki

2017-06-01

This study was to determine the incidence and risk factors of febrile neutropenia in chemotherapy-naïve Japanese patients treated systemically with etoposide plus platinum for lung cancer. The study was a retrospective analysis of 244 patients who were monitored for febrile neutropenia through multiple cycles of the combination of etoposide with platinum, and the associations between incidence of febrile neutropenia and patient characteristics were evaluated. Eighty-eight patients were treated with etoposide plus cisplatin and 156 were treated with etoposide plus carboplatin. Of the 244 patients treated, 198 (81.1%) completed 4 cycles for chemotherapy. Febrile neutropenia was observed in 48 of 244 patients (19.7%), including 18 of 88 (20.5%) patients who received etoposide plus cisplatin and 30 of 156 (19.2%) patients who received etoposide plus carboplatin. Grade 3 or 4 of neutropenia was experienced by a total of 208 patients (85.2%); 79 of 88 (89.8%) receiving etoposide plus cisplatin and 129 of 156 (82.7%) receiving etoposide plus carboplatin. Male gender and previous radiotherapy were identified by multivariate analysis as independent risk factors for febrile neutropenia. These results contrast with findings in Western patients and suggest that ethnic differences exist in the incidence of febrile neutropenia in patients receiving etoposide plus platinum chemotherapy. In addition, our results suggest that primary prophylaxis with granulocyte colony-stimulating factor should be considered for patients with these risk factors for febrile neutropenia prior to treatment with etoposide plus platinum.

[Epidemiology of febrile neutropenia in patients with hematological disease-a prospective multicentre survey in China].

PubMed

Yan, C H; Xu, T; Zheng, X Y; Sun, J; Duan, X L; Gu, J L; Zhao, C L; Zhu, J; Wu, Y H; Wu, D P; Hu, J D; Huang, H; Jiang, M; Li, J; Hou, M; Wang, C; Shao, Z H; Liu, T; Hu, Y; Huang, X J

2016-03-01

To investigate the incidence, clinical and microbiological features of febrile, and risk factors during neutropenia periods in patients with hematological diseases. From October 20, 2014 to March 20, 2015, consecutive patients who had hematological diseases and developed neutropenia during hospitalization were enrolled in the prospective, multicenter and observational study. A total of 784 episodes of febrile occurred in 1 139 neutropenic patients with hematological diseases. The cumulative incidence of febrile was 81.9% at 21 days after neutropenia. Multivariate analysis suggested that central venous catheterization (P<0.001, HR=3.407, 95% CI 2.276-4.496), gastrointestinal mucositis (P<0.001, HR=10.548, 95% CI 3.245-28.576), previous exposure to broad-spectrum antibiotics within 90 days (P<0.001, HR=3.582, 95% CI 2.387-5.770) and duration of neutropenia >7 days (P<0.001,HR=4.194, 95% CI 2.572-5.618) were correlated with higher incidence of febrile during neutropenia. With the increase of the risk factors, the incidence of febrile increased gradually (35.4%, 69.2%, 86.1%, 95.6%, P<0.001). Of 784 febrile cases, 253 (32.3%) were unknown origin, 429 (54.7% )of clinical documented infections and 102(13.0%) of microbiological documented infections. The most common sites of infection were pulmonary (49.5%), upper respiratory (16.0%), crissum (9.8%), blood stream (7.7%). The most common pathogens were gram-negative bacteria (44.54%), followed by gram-positive bacteria (37.99% ) and fungi (17.47% ). There was no significant difference in mortality rates between cases with febrile and cases without febrile (9.2% vs 4.8%, P=0.099). Multivariate analysis also suggested that >40 years old (P=0.047, HR=5.000, 95% CI 0.853-28.013), hemodynamic instability (P=0.001, HR=13.185, 95% CI 2.983-54.915), prior colonization or infection by resistant pathogens (P=0.005, HR=28.734, 95% CI 2.921-313.744), blood stream infection (P=0.038, HR=9.715, 95% CI 1.110-81.969) and pulmonary infection (P=0.031, HR=25.905, 95% CI 1.381-507.006) were correlated with higher mortality rate in cases with febrile. Febrile was the common complication during neutropenia periods in patients with hematological disease. There was different distribution of organisms in different sites of infection. Moreove, the duration of neutropenia >7 days, central venous catheterization, gastrointestinal mucositis and previous exposure to broad-spectrum antibiotics within 90 days were the risk factors for the higher incidence of febrile.

Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

ERIC Educational Resources Information Center

Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

2012-01-01

Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

[Febrile neutropenia in cancer patients: management in the emergency room].

PubMed

Rivera-Salgado, Daniel; Valverde-Muñoz, Kathia; Ávila-Agüero, María L

Febrile neutropenia is a life-threatening condition that requires immediate attention, especially in patients with chemotherapy-related neutropenia. Patients with febrile neutropenia have a much greater risk of developing bacterial disease, and fever may be the only indicator of severe bacterial infection. Adequate management of febrile neutropenia emphasizes early recognition of patients, risk stratification, and antibiotic therapy administration during the first 60 minutes of admission to an emergency room. Not all children with febrile neutropenia carry the same risk of morbidity and mortality, so in recent years, efforts have been made to distinguish between high-risk patients where more aggressive hospital management is required. In children classified as low-risk, outpatient management may be considered initially or after 72 hours, whilst high-risk patients should be hospitalized and managed with parenteral antibiotics.

Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: A cross-sectional observational study of 565 consecutive patients

PubMed Central

Snodgrass, Warren T.; Shah, Anjana; Yang, Mary; Kwon, Jeannie; Villanueva, Carlos; Traylor, Janelle; Pritzker, Karen; Nakonezny, Paul A.; Haley, Robert W.; Bush, Nicol Corbin

2013-01-01

Purpose To determine prevalence and risk factors for renal scar in children referred for urologic assessment of febrile UTI and/or VUR. Methods Pre-determined risk factors for renal scar were prospectively recorded in consecutive patients referred for UTI/VUR. Age, gender, VUR grade, and reported number of febrile and non-febrile UTIs were analyzed with logistic regression to determine risk for focal cortical defects on non-acute DMSA. Results Of 565 consecutive children, 24 (4%) had congenital renal dysplasia and 84 (15.5%) had focal defect(s). VUR, especially grades IV–V, recurrent febrile UTI, and older age increased risk. For any age child with the same number of UTIs, VUR increased odds of renal defect 5.4-fold (OR = 5.4, 95% CI = 2.7–10.6, AUC = 0.759). Conclusions Focal DMSA defects were present in 15.5% of 565 consecutive children referred for febrile UTI and/or VUR; 4% had presumed congenital reflux nephropathy without cortical defect. All VUR grades increased risk for these defects, as did recurrent febrile UTIs and older age. However, 43% with grades IV–V VUR and 76% with recurrent UTI had normal DMSA. PMID:23465483

Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: a cross-sectional observational study of 565 consecutive patients.

PubMed

Snodgrass, Warren T; Shah, Anjana; Yang, Mary; Kwon, Jeannie; Villanueva, Carlos; Traylor, Janelle; Pritzker, Karen; Nakonezny, Paul A; Haley, Robert W; Bush, Nicol Corbin

2013-12-01

To determine prevalence and risk factors for renal scar in children referred for urologic assessment of febrile UTI and/or VUR. Pre-determined risk factors for renal scar were prospectively recorded in consecutive patients referred for UTI/VUR. Age, gender, VUR grade, and reported number of febrile and non-febrile UTIs were analyzed with logistic regression to determine risk for focal cortical defects on non-acute DMSA. Of 565 consecutive children, 24 (4%) had congenital renal dysplasia and 84 (15.5%) had focal defect(s). VUR, especially grades IV-V, recurrent febrile UTI, and older age increased risk. For any age child with the same number of UTIs, VUR increased odds of renal defect 5.4-fold (OR = 5.4, 95% CI = 2.7-10.6, AUC = 0.759). Focal DMSA defects were present in 15.5% of 565 consecutive children referred for febrile UTI and/or VUR; 4% had presumed congenital reflux nephropathy without cortical defect. All VUR grades increased risk for these defects, as did recurrent febrile UTIs and older age. However, 43% with grades IV-V VUR and 76% with recurrent UTI had normal DMSA. Published by Elsevier Ltd.

Oral versus intravenous antibiotics in treatment of paediatric febrile neutropenia.

PubMed

Vedi, Aditi; Cohn, Richard

2013-03-01

The purpose of this study is to determine whether, in low-risk febrile neutropenic paediatric populations, oral antibiotics are as effective as intravenous antibiotics in obtaining resolution of the febrile neutropenic episode. A comprehensive literature search of MEDLINE, EMBASE and CENTRAL identified prospective, randomised controlled trials comparing oral antibiotics with intravenous antibiotics in the treatment of febrile neutropenic episodes in low-risk paediatric oncology patients. Outcomes assessed were mortality, rate of treatment failure, length of the febrile neutropenic episode and adverse events. The random effects model was used to calculate risk ratios (RRs) for dichotomous data and mean difference with standard deviation for continuous data. Seven trials were included in the overall analysis, which included 934 episodes of febrile neutropenia in 676 patients aged between 9 months and 20 years. The overall treatment failure rates were not significantly different between oral and intravenous antibiotics (RR: 1.02, 95% confidence interval 0.78-1.32, P= 0.91). In carefully selected low-risk febrile neutropenic children, empiric treatment with oral antibiotics is a safe and effective alternative to intravenous antibiotics as they lower the cost of treatment as well as psychosocial burden on these children and their families. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study

PubMed Central

2013-01-01

Background 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is effective and safe to suppress febrile seizures in children. Methods The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents. Prospect The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy. Trial registration ClinicalTrials.gov identifier: NCT01370044 PMID:23806032

Parental knowledge and perceptions of fever in children and fever management practices: differences between parents of children with and without a history of febrile seizures.

PubMed

Sakai, Rie; Niijima, Shinichi; Marui, Eiji

2009-04-01

The aim of this study was to compare maternal knowledge and perceptions of fever, fever management practices, and information sources of mothers of children with and without a history of febrile seizures. A questionnaire was used to survey mothers of children who visited health departments for a routine 18-month-old well baby check-up. A total of 386 responses were analyzed. More mothers of children with a history of febrile seizures than mothers of children without it stated that high fever caused febrile seizures and antipyretics prevented it. Fewer mothers of children with a history of febrile seizures than mothers in the other group thought that high fever caused brain damage and antipyretics prevented the disease from worsening and warmed the child's body during fever episode. Many mothers in both groups stated that they considered physicians to be their primary information source. Spouse and own parents were named as information sources among mothers of children with a history of febrile seizures, whereas books and the Internet were named in the other group. Mothers of children with a history of febrile seizures demonstrated a higher rate of accuracy in their knowledge of fever than those in the other group. Mothers of children with a history of febrile seizures used personal communication, whereas those in the other group relied on mass communication for health information. Providing accurate information to family members is essential to provide mothers with both accurate information and emotional support.

Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD.

PubMed

Bertelsen, Elin Næs; Larsen, Janne Tidselbak; Petersen, Liselotte; Christensen, Jakob; Dalsgaard, Søren

2016-08-01

Epilepsy, febrile seizures, and attention-deficit/hyperactivity disorder (ADHD) are disorders of the central nervous system and share common risk factors. Our goal was to examine the association in a nationwide cohort study with prospective follow-up and adjustment for selected confounders. We hypothesized that epilepsy and febrile seizures were associated with subsequent ADHD. A population-based cohort of all children born in Denmark from 1990 through 2007 was followed up until 2012. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) for ADHD were estimated by using Cox regression analysis, comparing children with epilepsy and febrile seizure with those without these disorders, adjusted for socioeconomic and perinatal risk factors, as well as family history of neurologic and psychiatric disorders. A total of 906 379 individuals were followed up for 22 years (∼10 million person-years of observation); 21 079 individuals developed ADHD. Children with epilepsy had a fully adjusted IRR of ADHD of 2.72 (95% CI, 2.53-2.91) compared with children without epilepsy. Similarly, in children with febrile seizure, the fully adjusted IRR of ADHD was 1.28 (95% CI, 1.20-1.35). In individuals with both epilepsy and febrile seizure, the fully adjusted IRR of ADHD was 3.22 (95% CI, 2.72-3.83). Our findings indicate a strong association between epilepsy in childhood and, to a lesser extent, febrile seizure and subsequent development of ADHD, even after adjusting for socioeconomic and perinatal risk factors, and family history of epilepsy, febrile seizures, or psychiatric disorders. Copyright © 2016 by the American Academy of Pediatrics.

Febrile Seizures and Behavioural and Cognitive Outcomes in Preschool Children: The Generation R Study

ERIC Educational Resources Information Center

Visser, Annemarie M.; Jaddoe, Vincent W. V.; Ghassabian, Akhgar; Schenk, Jacqueline J.; Verhulst, Frank C.; Hofman, Albert; Tiemeier, Henning; Moll, Henriette A.; Arts, Willem Frans M.

2012-01-01

Aim: General developmental outcome is known to be good in school-aged children who experienced febrile seizures. We examined cognitive and behavioural outcomes in preschool children with febrile seizures, including language and executive functioning outcomes. Method: This work was performed in the Generation R Study, a population-based cohort…

Febrile seizures: a population-based study.

PubMed

Dalbem, Juliane S; Siqueira, Heloise H; Espinosa, Mariano M; Alvarenga, Regina P

2015-01-01

To determine the prevalence of benign febrile seizures of childhood and describe the clinical and epidemiological profile of this population. This was a population-based, cross-sectional study, carried out in the city of Barra do Bugres, MT, Brazil, from August 2012 to August 2013. Data were collected in two phases. In the first phase, a questionnaire that was previously validated in another Brazilian study was used to identify suspected cases of seizures. In the second phase, a neurological evaluation was performed to confirm diagnosis. The prevalence was 6.4/1000 inhabitants (95% CI: 3.8-10.1). There was no difference between genders. Simple febrile seizures were found in 88.8% of cases. A family history of febrile seizures in first-degree relatives and history of epilepsy was present in 33.3% and 11.1% of patients, respectively. The prevalence of febrile seizures in Midwestern Brazil was lower than that found in other Brazilian regions, probably due to the inclusion only of febrile seizures with motor manifestations and differences in socioeconomic factors among the evaluated areas. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Increased interleukin-10 levels correlate with bacteremia and sepsis in febrile neutropenia pediatric oncology patients.

PubMed

Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

2012-03-01

Early diagnosis of bacteremia and sepsis in pediatric oncology patients with febrile neutropenia still remains unresolved task due to lack of sensitive and specific laboratory markers particularly at the beginning of the infectious process. The objective of our study was to assess the potentiality of interleukin-10 (IL-10) to predict or exclude bacteremia or sepsis at the beginning of febrile episode in childhood oncology patients. A total of 36 febrile neutropenic episodes in 24 children were studied. Serum samples were collected after confirmation of febrile neutropenia and analyzed using automated random access analyzer. The sensitivity of IL-10 was 73% and specificity - 92% (cut-off=18pg/ml, area under the curve - 0.87, 95% CI for sensitivity 39-94%, 95% CI for specificity 74-99%) with negative predictive value (NPV) - 83%. IL-10 evaluation might be used as an additional diagnostic tool for clinicians in excluding bacteremia or clinical sepsis in oncology patients with febrile neutropenia because of high NPV and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Serological diagnosis of hantavirus pulmonary syndrome in a febrile patient in Colombia.

PubMed

Mattar, Salim; Garzon, Denisse; Tadeu, Luis; Faccini-Martínez, Alvaro A; Mills, James N

2014-08-01

Hantavirus pulmonary syndrome (HPS) is an often fatal rodent-borne zoonosis caused by any of at least 20 hantavirus genotypes distributed throughout the Americas. Although HPS has been documented in several bordering countries, it has not been reported in Colombia. Here we report seroconversion to a hantavirus in paired samples from a hospitalized patient with symptoms compatible with HPS from Montería, Córdoba Department, north-western Colombia. Tests for regionally endemic agents including Plasmodium, Leptospira, Salmonella, dengue virus, Brucella, Rickettsia, human immunodeficiency virus and hepatitis viruses were negative. Because the patient was enrolled in a clinical trial for hemorrhagic fevers conducted by the University of Córdoba, serum samples were collected on admission and at discharge. Testing using Sin Nombre virus ELISA showed IgG and IgM seroconversion between samples. The eventual finding of this first clinical case of hantavirus infection in Colombia is consistent with the high prevalence of hantavirus antibodies in humans in the region and the likely exposure of the patient to rodents. The clinical presentation was similar to that found in neighbouring Panama. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Community Knowledge and Attitudes and Health Workers' Practices regarding Non-malaria Febrile Illnesses in Eastern Tanzania

PubMed Central

Chipwaza, Beatrice; Mugasa, Joseph P.; Mayumana, Iddy; Amuri, Mbaraka; Makungu, Christina; Gwakisa, Paul S.

2014-01-01

Introduction Although malaria has been the leading cause of fever for many years, with improved control regimes malaria transmission, morbidity and mortality have decreased. Recent studies have increasingly demonstrated the importance of non-malaria fevers, which have significantly improved our understanding of etiologies of febrile illnesses. A number of non-malaria febrile illnesses including Rift Valley Fever, dengue fever, Chikungunya virus infection, leptospirosis, tick-borne relapsing fever and Q-fever have been reported in Tanzania. This study aimed at assessing the awareness of communities and practices of health workers on non-malaria febrile illnesses. Methods Twelve focus group discussions with members of communities and 14 in-depth interviews with health workers were conducted in Kilosa district, Tanzania. Transcripts were coded into different groups using MaxQDA software and analyzed through thematic content analysis. Results The study revealed that the awareness of the study participants on non-malaria febrile illnesses was low and many community members believed that most instances of fever are due to malaria. In addition, the majority had inappropriate beliefs about the possible causes of fever. In most cases, non-malaria febrile illnesses were considered following a negative Malaria Rapid Diagnostic Test (mRDT) result or persistent fevers after completion of anti-malaria dosage. Therefore, in the absence of mRDTs, there is over diagnosis of malaria and under diagnosis of non-malaria illnesses. Shortages of diagnostic facilities for febrile illnesses including mRDTs were repeatedly reported as a major barrier to proper diagnosis and treatment of febrile patients. Conclusion Our results emphasize the need for creating community awareness on other causes of fever apart from malaria. Based on our study, appropriate treatment of febrile patients will require inputs geared towards strengthening of diagnostic facilities, drugs availability and optimal staffing of health facilities. PMID:24852787

Febrile seizures after 2009 influenza A (H1N1) vaccination and infection: a nationwide registry-based study.

PubMed

Bakken, Inger Johanne; Aaberg, Kari Modalsli; Ghaderi, Sara; Gunnes, Nina; Trogstad, Lill; Magnus, Per; Håberg, Siri Eldevik

2015-11-09

During the 2009 influenza A (H1N1) pandemic, a monovalent pandemic strain vaccine containing the oil-in-water adjuvant AS03 (Pandemrix®) was offered to the Norwegian population. The coverage among children reached 54%. Our aim was to estimate the risk of febrile seizure in children after exposure to pandemic influenza vaccination or infection. The study population comprised 226,889 children born 2006-2009 resident in Norway per October 1st, 2009. Febrile seizure episodes were defined by emergency hospital admissions / emergency outpatient hospital care with International Classification of Diseases, Version 10, codes R56.0 or R56.8. The self-controlled case series method was applied to estimate incidence rate ratios (IRRs) in pre-defined risk periods compared to the background period. The total observation window was ± 180 days from exposure day. Among 113,068 vaccinated children, 656 (0.6%) had at least one febrile seizure episode. The IRR of febrile seizures 1-3 days after vaccination was 2.00 (95% confidence interval [CI]: 1.15-3.51). In the period 4-7 days after vaccination, no increased risk was observed. Among the 8172 children diagnosed with pandemic influenza, 84 (1.0%) had at least one febrile seizure episode. The IRR of febrile seizures on the same day as a diagnosis of influenza was 116.70 (95% CI: 62.81-216.90). In the period 1-3 days after a diagnosis of influenza, a tenfold increased risk was observed (IRR 10.12, 95% CI: 3.82 - 26.82). In this large population-based study with precise timing of exposures and outcomes, we found a twofold increased risk of febrile seizures 1-3 days after pandemic influenza vaccination. However, we found that pandemic influenza infection was associated with a much stronger increase in risk of febrile seizures.

Management of chemotherapy-associated febrile neutropenia.

PubMed

Cameron, D

2009-09-01

The development of febrile neutropenia during a course of chemotherapy is not only a life-threatening complication, it can also lead to a decision to reduce chemotherapy intensity in subsequent treatment cycles, thus putting patient outcomes at risk. Although there are strategies available for the primary prevention of febrile neutropenia, these are not widely used in the UK management of breast cancer. It is, therefore, paramount to have a well thought out and rigorously implemented care protocol for febrile neutropenia, involving patients, family/carers and health-care professionals in both primary and secondary care, to ensure early detection and effective management.

Serum and CSF adiponectin, leptin, and interleukin 6 levels as adipocytokines in Egyptian children with febrile seizures: a cross-sectional study.

PubMed

Azab, Seham F; Abdalhady, Mohamed A; Almalky, Mohamed A A; Amin, Ezzat K; Sarhan, Dina T; Elhindawy, Eman M; Allah, Mayy A N; Elhewala, Ahmed A; Salam, Mohamed M A; Hashem, Mustafa I A; Soliman, Attia A; Akeel, Nagwa E; Abdellatif, Sawsan H; Elsamad, Nahla A; Rass, Anwar A; Arafat, Manal S

2016-04-12

A febrile seizure (FS) is the most common convulsive disorder in children. Activation of cytokine network is involved in FS pathogenesis. Adiponectin, leptin and IL-6 are the major adipocytokines secreted by fat cells. To date, only a few studies concerned the association of adipocytokines with febrile seizures. In this study, we tried to investigate serum and CSF levels of adiponectin, leptin, and interleukin-6 (IL-6); as adipocytokines, for the first time in Egyptian children with febrile seizures. This was a prospective cross-sectional study included one hundred patients with febrile seizure, and matched with age, gender, 100 children with febrile illness without seizures (febrile control, FC) and 100 healthy control group (HC). Serum and cerebrospinal fluid (CSF) levels of adiponectin, leptin, and (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) method. Serum adiponectin was significantly higher in children with FS (16.8 ± 3.7 ug/ml) and the FC group (18.3 ± 4.3 ug/ml) compared to the HC group (9.5 ± 2.2 ug/ml); P < 0.05, respectively. Serum leptin was significantly lower in children with FS (0.9 ± 0.3 ng/ml) compared to both the FC group (4.7 ± 1.2 ng/ml) and the HC group (1.8 ± 0.4 ng/ml); P < 0.01, respectively. Children with FS had significantly higher serum IL-6 levels (43.7 ± 11.7 ng/ml) than the FC group (21.9 ± 4.5 ng/ml) and the HC group (6.5 ± 1.8 ng/ml); P < 0.01, respectively. Patients with simple febrile seizures (SFS) had serum and CSF adiponectin levels similar to those with complex febrile seizures (CFS); (P > 0.05). Serum and CSF leptin levels were significantly lower in patients with CFS compared to the SFS group (P < 0.05). Serum and CSF IL-6 levels were significantly higher in patients with CFS compared to the SFS group (P < 0.01). On multivariate logistic regression analysis, the high serum IL-6 levels was the most significant risk factor associated with febrile seizures among studied children (OR: 6.2; 95 % CI: 3.58 -10.57; P = 0.0001). Our data brought a novel observation that some adipocytokines like leptin and IL-6 could be, at least in part, an aetiopathogenetic factor in the manifestation of febrile seizures in susceptible Egyptian children. Moreover, we observed a significant association between high CSF IL-6 levels and susceptibility to complex febrile seizures as did the low CSF leptin levels.

A prospectively validated nomogram for predicting the risk of chemotherapy-induced febrile neutropenia: a multicenter study.

PubMed

Bozcuk, H; Yıldız, M; Artaç, M; Kocer, M; Kaya, Ç; Ulukal, E; Ay, S; Kılıç, M P; Şimşek, E H; Kılıçkaya, P; Uçar, S; Coskun, H S; Savas, B

2015-06-01

There is clinical need to predict risk of febrile neutropenia before a specific cycle of chemotherapy in cancer patients. Data on 3882 chemotherapy cycles in 1089 consecutive patients with lung, breast, and colon cancer from four teaching hospitals were used to construct a predictive model for febrile neutropenia. A final nomogram derived from the multivariate predictive model was prospectively confirmed in a second cohort of 960 consecutive cases and 1444 cycles. The following factors were used to construct the nomogram: previous history of febrile neutropenia, pre-cycle lymphocyte count, type of cancer, cycle of current chemotherapy, and patient age. The predictive model had a concordance index of 0.95 (95 % confidence interval (CI) = 0.91-0.99) in the derivation cohort and 0.85 (95 % CI = 0.80-0.91) in the external validation cohort. A threshold of 15 % for the risk of febrile neutropenia in the derivation cohort was associated with a sensitivity of 0.76 and specificity of 0.98. These figures were 1.00 and 0.49 in the validation cohort if a risk threshold of 50 % was chosen. This nomogram is helpful in the prediction of febrile neutropenia after chemotherapy in patients with lung, breast, and colon cancer. Usage of this nomogram may help decrease the morbidity and mortality associated with febrile neutropenia and deserves further validation.

Febrile Seizures and Behavioural and Cognitive Outcomes in Preschool Children: An Old Issue Revisited

ERIC Educational Resources Information Center

Deonna, Thierry

2012-01-01

The possible deleterious role of febrile seizures on development is an old issue. It took a long time to realize that impaired development or occurrence of chronic epilepsy affected a very small minority of children with febrile seizures. These children either had pre-existing brain damage, specific genetic epileptic conditions, or seizure-induced…

Retrospective study for risk factors for febrile UTI in spinal cord injury patients with routine concomitant intermittent catheterization in outpatient settings.

PubMed

Mukai, S; Shigemura, K; Nomi, M; Sengoku, A; Yamamichi, F; Fujisawa, M; Arakawa, S

2016-01-01

Retrospective study. The objective of this study was to investigate the clinical risk factors for febrile urinary tract infection (UTI) in spinal cord injury-associated neurogenic bladder (NB) patients who perform routine clean intermittent catheterization (CIC). Rehabilitation Hospital, Kobe, Japan. Over a 3-year period, we retrospectively assessed the clinical risk factors for febrile UTI in 259 spinal cord injury patients diagnosed as NB and performing routine CIC with regard to the factors such as gender, the presence of pyuria and bacteriuria, and the categories of the American Spinal Injury Association (ASIA) impairment scale. A total of 67 patients had febrile UTI in the follow-up period, with 57 cases of pyelonephritis, 11 cases of epididymitis and 2 cases of prostatitis, including the patients with plural infectious diseases. The causative bacteria were ranked as follows: Escherichia coli (74 cases), Pseudomonas aeruginosa (17 cases), Enterococcus faecalis (14 cases) and Klebsiella pneumoniae (12 cases). Antibiotic-resistant E. coli were seen, with 10.5% instances of extended-spectrum β-lactamase (ESBL) production and 23.8% of fluoroquinolone resistance. Multivariate analyses of clinical risk factors for febrile UTI showed that gender (male, P=0.0431), and ASIA impairment scale C or more severe (P=0.0266) were significantly associated with febrile UTI occurrence in NB patients with routine CIC. Our data demonstrated gender (male) and ASIA impairment scale C or more severe were significantly associated with febrile UTI occurrence in NB patients using routine CIC. Further prospective studies are necessary to define the full spectrum of possible risk factors for febrile UTI in these patients.

Comparison of the MASCC and CISNE scores for identifying low-risk neutropenic fever patients: analysis of data from three emergency departments of cancer centers in three continents.

PubMed

Ahn, Shin; Rice, Terry W; Yeung, Sai-Ching J; Cooksley, Tim

2018-05-01

Patients with febrile neutropenia are a heterogeneous group with a minority developing serious medical complications. Outpatient management of low-risk febrile neutropenia has been shown to be safe and cost-effective. Scoring systems, such as the Multinational Association for Supportive Care in Cancer (MASCC) score and Clinical Index of Stable Febrile Neutropenia (CISNE), have been developed and validated to identify low-risk patients. We aimed to compare the performance of these two scores in identifying low-risk febrile neutropenic patients. We performed a pooled analysis of patients presenting with febrile neutropenia to three tertiary cancer emergency centers in the USA, UK, and South Korea in 2015. The primary outcome measures were the occurrence of serious complications. Admission to an intensive care unit (ICU) and 30-day mortality were secondary outcomes. The predictive performance of each score was analyzed. Five hundred seventy-one patients presented with febrile neutropenia. With MASCC risk index, 508 (89.1%) were classified as low-risk febrile neutropenia, compared to 60 (10.5%) with CISNE classification. Overall, the MASCC score had a greater discriminatory power in the detection of low-risk patients than the CISNE score (AUC 0.772, 95% CI 0.726-0.819 vs. 0.681, 95% CI 0.626-0.737, p = 0.0024). Both MASCC and CISNE scores have reasonable discriminatory value in predicting patients with low-risk febrile neutropenia. Risk scores should be used in conjunction with clinical judgment for the identification of patients suitable for outpatient management of neutropenic fever. Developing more accurate scores, validated in prospective settings, will be useful in facilitating more patients being managed in an outpatient setting.

Copeptin as a serum biomarker of febrile seizures.

PubMed

Stöcklin, Benjamin; Fouzas, Sotirios; Schillinger, Paula; Cayir, Sevgi; Skendaj, Roswitha; Ramser, Michel; Weber, Peter; Wellmann, Sven

2015-01-01

Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion. This was a prospective emergency-setting cross-sectional study of 161 children between six months and five years of age. Of these, 83 were diagnosed with febrile seizures, 69 had a febrile infection without seizures and nine had epileptic seizures not triggered by infection. Serum copeptin and prolactin levels were measured in addition to standard clinical, neurophysiological, and laboratory assessment. NCT01884766. Circulating copeptin was significantly higher in children with febrile seizures (median [interquartile range] 18.9 pmol/L [8.5-36.6]) compared to febrile controls (5.6 pmol/L [4.1-9.4]; p < 0.001), with no differences between febrile and epileptic seizures (21.4 pmol/L [16.1-46.6]; p = 0.728). In a multivariable regression model, seizures were the major determinant of serum copeptin (beta 0.509; p < 0.001), independently of clinical and baseline laboratory indices. The area under the receiver operating curve for copeptin was 0.824 (95% CI 0.753-0.881), significantly higher compared to prolactin (0.667 [0.585-0.742]; p < 0.001). The diagnostic accuracy of copeptin increased with decreasing time elapsed since the convulsive event (at 120 min: 0.879 [0.806-0.932] and at <60 min: 0.975 [0.913-0.997]). Circulating copeptin has high diagnostic accuracy in febrile seizures and may be a useful adjunct for accurately diagnosing postictal states in the emergency setting.

Comparison of piperacillin tazobactam and cefoperazone sulbactam monotherapy in treatment of febrile neutropenia.

PubMed

Karaman, Serap; Vural, Sema; Yildirmak, Yildiz; Emecen, Merve; Erdem, Ela; Kebudi, Rejin

2012-04-01

Monotherapy has tended to replace the combination therapy in emprical treatment of febrile neutropenia. There is no reported trial which compares the efficacy of cefoperazone-sulbactam (CS) and piperacillin-tazobactam (PIP/TAZO) monotherapies in the treatment of febrile neutropenia. In this prospective randomized study, we aimed to compare the safety and efficacy of CS versus PIP/TAZO as empirical monotherapies in febrile neutropenic children with cancer. The study included febrile, neutropenic children hospitalized at our center for cancer. They were randomly selected to receive CS 100 mg/kg/day or PIP/TAZO 360 mg/kg/day. Duration of fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between the two groups. Resolution of fever without antibiotic change was defined as success and resolution of fever with antibiotic change or death of a patient was defined as failure. Modification was defined as changing the empirical antimicrobial agent during a febrile episode. One hundred and two febrile neutropenic episodes were documented in 55 patients with a median age of 4 years. In 50 episodes CS and in 52 episodes PIP/TAZO was used. Duration of fever and neutropenia, neutrophil count, age, sex, and primary disease were not different between two groups. Success rates in the CS and PIP/TAZO groups were respectively 56 and 62% (P > 0.05). Modification rate between two groups showed no significant difference (P > 0.05). No serious adverse effect occurred in either of the groups. CS and PIP/TAZO monotherapy are both safe and effective in the initial treatment of febrile neutropenia in children with cancer. Copyright © 2011 Wiley Periodicals, Inc.

Reducing Uncertainty for Acute Febrile Illness in Resource-Limited Settings: The Current Diagnostic Landscape

PubMed Central

Robinson, Matthew L.; Manabe, Yukari C.

2017-01-01

Diagnosing the cause of acute febrile illness in resource-limited settings is important—to give the correct antimicrobials to patients who need them, to prevent unnecessary antimicrobial use, to detect emerging infectious diseases early, and to guide vaccine deployment. A variety of approaches are yielding more rapid and accurate tests that can detect more pathogens in a wider variety of settings. After decades of slow progress in diagnostics for acute febrile illness in resource-limited settings, a wave of converging advancements will enable clinicians in resource-limited settings to reduce uncertainty for the diagnosis of acute febrile illness. PMID:28719277

Incidental Detection of Dent-2 Disease in an Infant with "Febrile Proteinuria".

PubMed

Salihu, Shpetim; Tosheska, Katerina; Cekovska, Svetlana; Tasic, Velibor

2018-05-17

Febrile proteinuria is functional proteinuria and is seen as a transitory phenomenon during acute febrile illness, mainly viral infections. It is a benign phenomenon and clears promptly with resolution of the infection. In this report, we present a patient who was thought to have febrile proteinuria. Persistence of significant proteinuria after resolution of the infection prompted biochemical and genetic work-up which lead to the diagnosis of Dent-2 disease. We recommend the use of sodium dodecyl sulphate electropheresis (SDS-PAGE) for the detection of low molecular weight proteinuria. ©2018The Author(s). Published by S. Karger AG, Basel.

The effect of low ambient temperature on the febrile responses of rats to semi-purified human endogenous pyrogen.

PubMed

Stitt, J T; Shimada, S G

1985-01-01

The febrile responses of Sprague-Dawley rats to semi-purified human endogenous pyrogen were studied at a thermoneutral ambient temperature (26 degrees C) and in the cold (3 degrees C). It was found that while rats developed typical monophasic febrile responses at thermoneutrality, febrile responses were absent in the cold-exposed rats. Experiments were conducted to determine whether this lack of febrile responses in cold-exposed rats was due to an inability of these animals to generate or retain heat in the cold. Thermogenesis and vasoconstriction were stimulated in cold-exposed rats by selectively cooling the hypothalamus, using chronically implanted thermodes. It was shown that, using this stimulus, metabolic rate could be increased by more than 50 percent and body temperature could be driven up at a rate of 5 degrees C/hour in rats exposed to the cold. Therefore, it was concluded that the lack of febrile responses of cold-exposed rats to pyrogen is in no way due to a physical or physiological inability to retain heat. Instead, it appears that in some manner cold exposure suppresses the sensitivity or responsiveness of the rat to pyrogenic stimuli.

[Clinical significance of peak body temperature, white blood cell count, and C-reactive protein level in febrile episodes among geriatric inpatients].

PubMed

Ikematsu, H; Nabeshima, A; Yamaga, S; Yamaji, K; Kakuda, K; Ueno, K; Hayashi, J; Shirai, T; Hara, H; Kashiwagi, S

1997-06-01

To investigate the clinical implication of peak body temperature, peripheral blood white blood cell (WBC) count, and serum C-reactive protein (CRP) level in febrile symptoms among geriatric hospitalized patients, they were analyzed in 968 febrile episodes obtained from 433 hospitalized patients in the referred hospital. Episodes of one day duration were most frequent (41.6%). WBC count was elevated over 8000/microliters in 475 episodes (49.1%) and CRP exceeded 1.0 mg/dl in 770 episodes (79.5%). Frequency of WBC elevation decreased and frequency of CRP elevation increased according to the time course. The mean value of CRP increased significantly according to the time course. The frequency of WBC count increase and CRP elevation and their averages correlated to the peak body temperature. The peak body temperature displayed the most striking correlation to the length of febrile episodes among three clinical indicators, peak body temperature, WBC count, and CRP level. These results indicate that the elevation of WBC count and/or CRP level is frequent in geriatric patients with febrile symptoms. Peak body temperature may serve as a clinical indicator of the severy of the febrile disease occurring in geriatric patients.

[Dengue infection: A common cause of febrile syndrome in patients from Quibdó, Chocó, Colombia].

PubMed

Restrepo, Berta Nelly; Piedrahita, Leidy Diana; Agudelo, Ivony Yireth; Marín, Katherine; Ramírez, Ruth

2015-01-01

Quibdó, a municipality in Chocó, has poor public services and weather and social conditions that favor dengue transmission. However, there are few studies about this problem in this district. To determine the frequency of dengue infection in patients with acute febrile syndrome and to compare clinical features among dengue infected patients with other febrile diseases. A cross-sectional study was conducted from January, 2008, to March, 2010. The study population comprised patients with febrile syndrome of seven or fewer days of evolution, recruited from hospitals in the town. Dengue diagnosis was made in serum samples by detection of IgM antibodies, NS1 antigen, reverse transcription polymerase chain reaction, and virus isolation. Clinical and laboratory information from the patients was obtained. During the study period, 469 patients with acute febrile syndrome were recruited, of whom 98.3% were Afro-descendant. Dengue fever was found in 28.4% of the cases. Four dengue serotypes were identified with DENV-1 predominance. The ages ranged from zero to 76 years. From all patients, 70.7% of cases were classified as dengue without warning signs. Nausea, vomiting, abdominal pain, cough, nasal congestion and sore throat were significantly more frequent in patients with another febrile disease. Active surveillance of the acute febrile syndrome allowed for the detection of undiagnosed cases of dengue; the observed frequency of this infection suggests that the study area has a high risk of dengue infection.

Febrile neutropaenia in cancer patients.

PubMed

Walwyn, M; Nicholson, A; Lee, M G; Wharfe, G; Frankson, M A

2010-03-01

Febrile neutropaenia is a common complication of chemotherapy in cancer patients. Empirical antibiotic regimes are based on the epidemiological characteristics of bacterial isolates globally and locally. This study retrospectively reviewed all cases of febrile neutropaenia in patients with confirmed cancer admitted at the University Hospital of the West Indies in the four-year period between, January 1, 2003 and December 31, 2006 and who received chemotherapy. Cases were identified from blood culture records and hospital charts which were reviewed to determine the aetiological agents causing bacteraemia, their antimicrobial susceptibilities and clinicalfeatures. These cases were compared with non-neutropaenic cancer patients admitted with fever. A total of 197 febrile episodes in cancer patients were reviewed. Thirty-seven per cent had febrile neutropaenia while 62% were non-neutropaenic. Acute myeloid leukaemia was the most common haematological malignancy and the most common solid tumour was breast cancer. Twenty-six per cent of patients had a positive blood culture. In febrile neutropaenic patients, Escherichia coli was the most common organism isolated followed by coagulase-negative staphylococci while in non-neutropaenic patients, coagulase-negative staphylococci was most common. Acinetobacter infections was prominent in non-neutropaenic patients but absent in neutropaenic patients. More than one organism was cultured in 9 neutropaenic and 18 non-neutropaenic patients. Mortality was 10.8% in neutropaenic and 24.4% in non-neutropaenic patients. Gram-negative organisms are the predominant isolates in febrile neutropaenic episodes in this cohort of patients. Non-neutropaenic patients had an increased mortality with an increase in Acinetobacter infections and multiple isolates.

Sistemas Correctores de Campo Para EL Telescopio Ritchey-Chretien UNAM212

NASA Astrophysics Data System (ADS)

Cobos, F. J.; Galan, M. J.

1987-05-01

El telescopio UNAM2l2 fue inaugurado hace siete años y concebido para trabajar en las razones focales: f/7.5, F/13.5, F/27 y F/98. El diseño Ritchey-Chretién corresponde a la razón focal F/7.5 y el foco primario (F/2.286) no se consideró como utilizable para fotografía directa. En el Instituto de Astronomía de la UNAM, se diseñó y construyó un sistema corrector de campo para la razón focal F/7.5, que actualmente está en funcionamiento. Dentro de un programa de colaboración en diseflo y evaluación de sistemas ópticos, entre el Instituto de Astrofísica de Canarias y el Instituto de Astronomía de la UNAM, decidimos intentar el diseño de una correctora de campo para el foco primario del tȩlescopio UNAM212 bajo la consideración de que no son insalvables los problemas que implicaría su instalación y de que es muy posible que, en un futuro relativamente cercano, podamom tener un detector bidimenmional tipo Mepsicrón cuya área sensible haga tentadora la idea de construir la cámara directa para foco primario

G-CSF in solid tumor chemotherapy: a tailored regimen reduces febrile neutropenia, treatment delays and direct costs.

PubMed

Tsavaris, Nicolas; Kosmas, Christos; Gouveris, Panagiotis; Vadiak, Maria; Dimitrakopoulos, Antonis; Karadima, Dimitra; Pagouni, Efterpi; Panagiotakopoulos, George; Tzima, Evanthia; Ispoglou, Sevasti; Sakelariou, Dimitris; Koufos, Christos

2004-02-01

Current guidelines do not recommend G-CSF for patients with risk factors for neutropenia. One-hundred patients undergoing chemotherapy were randomized to treatment with G-CSF at 5 Kg/kg for established febrile neutropenia (ANC <1000/microl) (Group A) or G-CSF at 263 Kg/day if ANC was 1500/microl or less on the day of the expected nadir, with the duration of treatment determined by the severity of neutropenia (Group B). The number of doses of G-CSF was similar in the two groups. There were 34 cases of febrile neutropenia in Group A, but none in Group B (p=0.0001). Hospital admission for febrile neutropenia, antibiotic use and delays in chemotherapy were all significantly more common in Group A. Total direct costs were estimated to be 66, 646 for Group A and 47, 119 for Group B. Tailoring treatment does not increase G-CSF use, but significantly reduces febrile neutropenia and treatment delays and lowers direct costs.

Serological evidence of arboviral infection and self-reported febrile illness among U.S. troops deployed to Al Asad, Iraq.

PubMed

Riddle, M S; Althoff, J M; Earhart, K; Monteville, M R; Yingst, S L; Mohareb, E W; Putnam, S D; Sanders, J W

2008-05-01

Understanding the epidemiology of current health threats to deployed U.S. troops is important for medical assessment and planning. As part of a 2004 study among U.S. military personnel deployed to Al Asad Air Base, in the western Anbar Province of Iraq, over 500 subjects were enrolled, provided a blood specimen, and completed a questionnaire regarding history of febrile illness during this deployment (average approximately 4 months in country). This mid-deployment serum was compared to pre-deployment samples (collected approximately 3 months prior to deployment) and evaluated for seroconversion to a select panel of regional arboviral pathogens. At least one episode of febrile illness was reported in 84/504 (17%) of the troops surveyed. Seroconversion was documented in nine (2%) of deployed forces tested, with no association to febrile illness. Self-reported febrile illness was uncommon although often debilitating, and the risk of illness due to arbovirus infections was relatively low.

Shivering in Febrile Children: Frequency and Usefulness in Predicting Serious Bacterial Infections - A Prospective Case-Control Study.

PubMed

Erell, Yair; Youngster, Ilan; Abu-Kishk, Ibrahim; Kozer, Eran

2017-11-01

A prospective case-control study was conducted in a pediatric emergency department to describe the proportion of febrile children experiencing shivering and its clinical significance. Shivering was reported in 186 of 645 febrile children (28.8%). The rate of serious bacterial infection was similar in 86 children with shivering and 86 matched controls. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update

PubMed Central

Villafuerte-Gutierrez, Paola; Villalon, Lucia; Losa, Juan E.; Henriquez-Camacho, Cesar

2014-01-01

Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis. PMID:25525436

Factors Associated with Hospital Length of Stay among Cancer Patients with Febrile Neutropenia

PubMed Central

Rosa, Regis G.; Goldani, Luciano Z.

2014-01-01

Purpose This study sought to evaluate factors associated with hospital length of stay in cancer patients with febrile neutropenia. Methods A prospective cohort study was performed at a single tertiary referral hospital in southern Brazil from October 2009 to August 2011. All adult cancer patients with febrile neutropenia admitted to the hematology ward were evaluated. Stepwise random-effects negative binomial regression was performed to identify risk factors for prolonged length of hospital stay. Results In total, 307 cases of febrile neutropenia were evaluated. The overall median length of hospital stay was 16 days (interquartile range 18 days). According to multiple negative binomial regression analysis, hematologic neoplasms (P = 0.003), high-dose chemotherapy regimens (P<0.001), duration of neutropenia (P<0.001), and bloodstream infection involving Gram-negative multi-drug-resistant bacteria (P = 0.003) were positively associated with prolonged hospital length of stay in patients with febrile neutropenia. The condition index showed no evidence of multi-collinearity effect among the independent variables. Conclusions Hematologic neoplasms, high-dose chemotherapy regimens, prolonged periods of neutropenia, and bloodstream infection with Gram-negative multi-drug-resistant bacteria are predictors of prolonged length hospital of stay among adult cancer patients with febrile neutropenia. PMID:25285790

The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia.

PubMed

Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

2013-04-01

Prediction of bacteremia/sepsis in childhood oncology patients with febrile neutropenia still remains a challenge for the medical community due to the lack of reliable biomarkers, especially at the beginning of infectious process. The objective of this study was to evaluate diagnostic value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, HLA-G) and procalcitonin (PCT) in the identification of infectious process at the beginning of a febrile episode in pediatric oncology patients. A total of 62 episodes of febrile neutropenia in 37 childhood oncology patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to recommendations of manufacturers. Patients were classified into bacteremia/sepsis and fever of unknown origin groups. Median of PCT and sIL-2R were considerably higher in bacteremia/sepsis group compared to fever of unknown origin group, whereas median of sHLA-G and presepsin levels between investigated groups did not differ sufficiently. PCT and sIL-2R determination might be used as an additional diagnostic tool for the detection of bacteremia/sepsis in childhood oncology patients with febrile neutropenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microbial translocation contribute to febrile episodes in adults with chemotherapy-induced neutropenia.

PubMed

Wong, Michelle; Barqasho, Babilonia; Ohrmalm, Lars; Tolfvenstam, Thomas; Nowak, Piotr

2013-01-01

In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).

Febrile status epilepticus due to respiratory syncytial virus infection.

PubMed

Uda, Kazuhiro; Kitazawa, Katsuhiko

2017-08-01

Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae. © 2017 Japan Pediatric Society.

Exposure to traffic noise and air pollution and risk for febrile seizure: a cohort study.

PubMed

Hjortebjerg, Dorrit; Nybo Andersen, Anne-Marie; Ketzel, Matthias; Raaschou-Nielsen, Ole; Sørensen, Mette

2018-03-25

Objectives Exposure to traffic noise and air pollution is suspected to increase susceptibility to viral infections - the main triggering factor for febrile seizures. No studies have examined these two exposures in relation to febrile seizures. We aimed to investigate whether exposure to road traffic noise and air pollution are associated with risk of febrile seizures in childhood. Methods From our study base of 51 465 singletons from a national birth cohort, we identified 2175 cases with febrile seizures using a nationwide registry. Residential address history from conception to six years of age were found in national registers, and road traffic noise (L den ) and air pollution (NO 2 ) were modeled for all addresses. Analyses were done using Cox proportional hazard model with adjustment for potential confounders, including mutual exposure adjustment. Results An interquartile range (IQR) increase in childhood exposure to road traffic noise and air pollution was associated with an 11% [incidence rate ratio (IRR) 1.11, 95% confidence interval (CI) 1.04-1.19) and 5% (IRR 1.05, 95% CI 1.02-1.07) higher risk for febrile seizures, respectively, after adjustment for potential confounders. Weaker tendencies were seen for pregnancy exposure. In models with mutual exposure adjustment, the estimates were slightly lower, with IRR of 1.08 (95% CI 1.00-1.16) and 1.03 (95% CI 0.99-1.06) per IQR increase in childhood exposure to road traffic noise and air pollution, respectively. Conclusions This study suggests that residential exposure to road traffic noise and air pollution is associated with higher risk for febrile seizures.

IL-10 combined with procalcitonin improves early prediction of complications of febrile neutropenia in hematological patients.

PubMed

Vänskä, Matti; Koivula, Irma; Jantunen, Esa; Hämäläinen, Sari; Purhonen, Anna-Kaisa; Pulkki, Kari; Juutilainen, Auni

2012-12-01

Early diagnosis of complicated course in febrile neutropenia is cumbersome due to the non-specificity of clinical and laboratory signs of severe infection. This prospective study included 100 adult hematological patients with febrile neutropenia after intensive chemotherapy at the onset of fever (d0) and for 3 days (d1-d3) thereafter. The study aim was to find early predictors for complicated course of febrile neutropenia, defined as bacteremia or septic shock. Interleukin 6 (IL-6), interleukin 10 (IL-10), procalcitonin (PCT) and C-reactive protein (CRP) all predicted complicated course of febrile neutropenia on d0, but only PCT was predictive throughout the study period. For IL-10 on d0-1 with cut-off 37 ng/L, sensitivity was 0.71, specificity 0.82, positive predictive value 0.52 and negative predictive value 0.92. For PCT on d0-1 with cut-off 0.13 μg/L, the respective measures were 0.95, 0.53, 0.36, and 0.98. For the combination of IL-10 and PCT on d0-1 with the same cut-offs, specificity improved to 0.85 and positive predictive value to 0.56. In conclusion, the present study confirms the high negative predictive value of PCT and provides new evidence for IL-10 as an early predictor for complicated course of febrile neutropenia in hematological patients. Combining IL-10 with PCT improves the early prediction for complicated course of febrile neutropenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Abstract Interface Specifications for the A-7E Device Interface Module.

DTIC Science & Technology

1980-11-20

Undesired events +GSINSAGE+ pl:time;O !+SINS attitude age +! %SINS not enabled% p2 :time:O !+SINS position age +! p3:time:O !+SINS velocity age +! +G SINS...attitude age +! The elapsed time since new valid attitude data was provided by the SINS hardware. !+SINS attitude valid+! True iff SINS attitude data is valid...horizontal plane. !+SINS position age +! The elapsed time since new valid position data was provided by the SINS hardware. !+SINS position valid+! True iff

Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection.

PubMed

Alexander, Siobhan E; Arlen, Angela M; Storm, Douglas W; Kieran, Kathleen; Cooper, Christopher S

2015-04-01

Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Assessment of the levels of serum Hsp 70 and ghrelin in children with simple febrile convulsions.

PubMed

Kilic, Mehmet; Gündüzalp, Mehmet; Taskin, Erdal; Aydin, Süleyman; Serin, Hepsen M

2016-04-01

In this study we aimed to evaluate the serum levels of Heat-shock protein (Hsp) 70 and acylated and desacylated ghrelin in patients suffering from a simple febrile convulsion. This cross-sectional study included patients who were diagnosed with a simple febrile convulsion, afebrile tonic-clonic epileptic seizure and upper respiratory tract infection when admitted to our hospital. All patients were aged between six months and 60 months. Patients enrolled in this study were divided into five groups. Group I: patients with a simple febrile convulsion and body temperature of 38º C to 39° C; group II: patients with a simple febrile convulsion and body temperature of 39.1° C to 41° C; group III: patients with primary generalised tonic-clonic seizure and normal body temperature; group IV: patients with upper respiratory infection without convulsion and a body temperature of 38° C to 39° C; and group V: patients with upper respiratory infection without convulsion and a body temperature of 39.1° C to 41° C. The control group included healthy children who were followed up in the healthy children polyclinic. Serum levels of Hsp70 and acylated and des-acylated ghrelin were studied from the blood samples collected from the patients and control group. Serum levels of Hsp70 were higher in the febrile convulsion (groups I, II) and epileptic convulsion and infection (groups IV, V) groups than in the controls (P<0.0001). Moreover, serum levels of acylated and desacylated ghrelin were higher in the simple febrile convulsion (groups I and II) and epileptic convulsion and infection (groups IV and V) groups than in the control (P<0.05). We demonstrated that serum levels of Hsp70 and acylated and desacylated ghrelin increased in patients with a simple febrile convulsion.

Urine interleukin-6, interleukin-8 and transforming growth factor β1 in infants with urinary tract infection and asymptomatic bacteriuria

PubMed Central

Krzemień, Grażyna; Turczyn, Agnieszka; Pańczyk-Tomaszewska, Małgorzata

2016-01-01

Introduction Urinary tract infection (UTI) occurs in 1.1% of girls and 1.4% of boys during the first year of life. Asymptomatic bacteriuria (ABU) is usually detected incidentally in 0.9% of girls and 2.5% of boys at this age. The aim of the study was to assess the usefulness of measurement of pro-inflammatory urine interleukin (IL)-6 and IL-8 concentrations and anti-inflammatory transforming growth factor β1 (TGF-β1) level in infants with febrile UTI, non-febrile UTI and ABU. Material and methods A total of 35 children, mean age 6.14 ±3.47 months, were divided into three groups: group I – febrile UTI (n = 13), group II – non-febrile UTI (n = 13) and group III – ABU (n = 9). At the time of enrollment urine IL-6, IL-8, TGF-β1 and serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) were measured. Renal ultrasound was performed in all children, 99mTc-dimercaptosuccinic acid scintigraphy (DMSA) and voiding cystourethrography in children with UTI. Results Urine concentrations of IL-6 and IL-8 were significantly higher in febrile UTI compared to those with non-febrile UTI and ABU (p < 0.5, p < 0.01) and positively correlated with CRP, ESR and WBC (p < 0.01). Urine levels of TGF-β1 were significantly higher in children with febrile UTI compared to those with ABU (p < 0.05) and positively correlated with WBC (p < 0.01). Inflammatory changes in the DMSA scan were detected in 66.6% of children with UTI. No significant difference in frequency of an abnormal DMSA scan compared to a normal scan was found in groups with febrile and non-febrile UTI. No relations between urine cytokines, systemic inflammatory markers and changes in DMSA scan were observed. The cutoff value for detection of inflammatory changes in the DMSA scan for IL-8 was 120 pg/mg creatinine (Cr) and 40 pg/mg Cr for TGF-β1. Based on this value, the sensitivity for IL-8 was 58.3%, specificity 100% and for TGF-β1 66.7% and 83.7%, respectively. Conclusions We found significant differences in children with febrile UTI and ABU regarding urine IL-6, IL-8 and TGF-β1 levels. Urine cytokines and systemic inflammatory markers do not differentiate between upper and lower UTI in infants. PMID:27833443

Annual Progress Summary Report for Grant N00014-89-J-3073 (Massachusetts General Hospital)

DTIC Science & Technology

1992-11-15

release of thromboxane and the subsequent pulmonary vasoconstriction and hypertension as well as the febrile response and leukopenia; 2) in-vitro...this mixture as measured by a decreased febrile response with a single temperature peak and a briefer leukopenia. However there was no reduc- tion of the...release and physiologically important acute pulmonary vasoconstriction and hypertension, as well as the sys- temic effects of a biphasic febrile response

Disparities between malaria infection and treatment rates: Evidence from a cross-sectional analysis of households in Uganda.

PubMed

Saran, Indrani; Cohen, Jessica

2017-01-01

In Sub-Saharan Africa, both under-treatment and over-treatment of malaria are common since illnesses are often diagnosed and treated on the basis of symptoms. We investigate whether malaria treatment rates among febrile individuals correspond to observed patterns of malaria infection by age and by local prevalence. We use data on treatment of febrile illnesses from a household survey that was conducted between March and May 2012 in 92 villages in six districts in Eastern Uganda. All household members were also tested for malaria using a rapid diagnostic test. We show that both the age of the febrile individual and the village prevalence rate are strongly associated with the odds that a febrile patient was infected with malaria, but not with the odds of ACT treatment. Compared to individuals who were aged 15 or above, febrile individuals aged 5-14 had 3.21 times the odds of testing positive for malaria (95% CI: [2.36 4.37], P<0·001), and febrile individuals who were under age 5 had 2.66 times the odds of testing positive for malaria (95% CI: [1.99 3.56], P<0·001). However, ACT treatment rates for febrile illnesses were not significantly higher for either children ages 5-14 (Unadjusted OR: 1.19, 95% CI: [0.88 1.62], P = 0.255) or children under the age of 5 (Unadjusted OR: 1.24, 95% CI: [0.92 1.68], P = 0·154). A one standard deviation increase in the village malaria prevalence rate was associated with a 2.03 times higher odds that a febrile individual under the age of five tested positive for malaria (95% CI: [1.63 2.54], p<0·001), but was not significantly associated with the odds of ACT treatment (Un-adjusted OR: 0.83, 95% CI: [0.66 1.05], P = 0·113). We present some evidence that this discrepancy may be because caregivers do not suspect a higher likelihood of malaria infection, conditional on fever, in young children or in high-prevalence villages. Our findings suggest that households have significant mis-perceptions about malaria likelihood that may contribute to the under-treatment of malaria. Policies are needed to encourage caregivers to seek immediate diagnostic testing and treatment for febrile illnesses, particularly among young children.

Prediction of Cortical Defect Using C-Reactive Protein and Urine Sodium to Potassium Ratio in Infants with Febrile Urinary Tract Infection

PubMed Central

Jung, Su Jin

2016-01-01

Purpose We investigated whether C-reactive protein (CRP) levels, urine protein-creatinine ratio (uProt/Cr), and urine electrolytes can be useful for discriminating acute pyelonephritis (APN) from other febrile illnesses or the presence of a cortical defect on 99mTc dimercaptosuccinic acid (DMSA) scanning (true APN) from its absence in infants with febrile urinary tract infection (UTI). Materials and Methods We examined 150 infants experiencing their first febrile UTI and 100 controls with other febrile illnesses consecutively admitted to our hospital from January 2010 to December 2012. Blood (CRP, electrolytes, Cr) and urine tests [uProt/Cr, electrolytes, and sodium-potassium ratio (uNa/K)] were performed upon admission. All infants with UTI underwent DMSA scans during admission. All data were compared between infants with UTI and controls and between infants with or without a cortical defect on DMSA scans. Using multiple logistic regression analysis, the ability of the parameters to predict true APN was analyzed. Results CRP levels and uProt/Cr were significantly higher in infants with true APN than in controls. uNa levels and uNa/K were significantly lower in infants with true APN than in controls. CRP levels and uNa/K were relevant factors for predicting true APN. The method using CRP levels, u-Prot/Cr, u-Na levels, and uNa/K had a sensitivity of 94%, specificity of 65%, positive predictive value of 60%, and negative predictive value of 95% for predicting true APN. Conclusion We conclude that these parameters are useful for discriminating APN from other febrile illnesses or discriminating true APN in infants with febrile UTI. PMID:26632389

Dipstick screening for urinary tract infection in febrile infants.

PubMed

Glissmeyer, Eric W; Korgenski, E Kent; Wilkes, Jacob; Schunk, Jeff E; Sheng, Xiaoming; Blaschke, Anne J; Byington, Carrie L

2014-05-01

This study compares the performance of urine dipstick alone with urine microscopy and with both tests combined as a screen for urinary tract infection (UTI) in febrile infants aged 1 to 90 days. We queried the Intermountain Healthcare data warehouse to identify febrile infants with urine dipstick, microscopy, and culture performed between 2004 and 2011. UTI was defined as >50 000 colony-forming units per milliliter of a urinary pathogen. We compared the performance of urine dipstick with unstained microscopy or both tests combined ("combined urinalysis") to identify UTI in infants aged 1 to 90 days. Of 13 030 febrile infants identified, 6394 (49%) had all tests performed and were included in the analysis. Of these, 770 (12%) had UTI. Urine culture results were positive within 24 hours in 83% of UTIs. The negative predictive value (NPV) was >98% for all tests. The combined urinalysis NPV was 99.2% (95% confidence interval: 99.1%-99.3%) and was significantly greater than the dipstick NPV of 98.7% (98.6%-98.8%). The dipstick positive predictive value was significantly greater than combined urinalysis (66.8% [66.2%-67.4%] vs 51.2% [50.6%-51.8%]). These data suggest 8 febrile infants would be predicted to have a false-positive combined urinalysis for every 1 infant with UTI initially missed by dipstick screening. Urine dipstick testing compares favorably with both microscopy and combined urinalysis in febrile infants aged 1 to 90 days. The urine dipstick test may be an adequate stand-alone screen for UTI in febrile infants while awaiting urine culture results. Copyright © 2014 by the American Academy of Pediatrics.

Predictors of chemoradiation related febrile neutropenia prophylaxis in older adults - Experience from a limited resource setting.

PubMed

Gangopadhyay, Aparna

2018-01-01

To identify risk factors that lower efficacy of antibiotic prophylaxis of febrile neutropenia among older patients on chemoradiation. Audit of institutional data showed that older adults are at higher risk of febrile neutropenia during chemoradiation. In limited resource settings widespread use of Granulocyte-Colony Stimulating Factor (G-CSF) is not economically feasible and antibiotics are used commonly. Despite compliance with antibiotics, prophylaxis is inadequate in many patients owing to patient and tumor related factors. Data from records of 219 older patients receiving antibiotic prophylaxis during chemoradiation were studied. Baseline assessment data and predisposing factors for febrile neutropenia were recorded. All patients received prophylactic fluoroquinolones. Incidence of febrile neutropenia and association with predisposing factors at baseline was analyzed by multiple logistic regression. 38.4% developed febrile neutropenia despite compliance. Multiple logistic regression revealed geriatric assessment (G8) score and tumor stage to be significant predictors of febrile neutropenia while on antibiotics ( p  < 0.0001). Odds ratios for two significant predictors G8 score and tumor stage, respectively, were 2.9 (95% CI 1.8036-4.6815) and 2.7 (95% CI 1.7501-4.1318). Correlation between these two significant predictors was found to be low in our cohort (Spearman's coefficient of rank correlation (rho) - 0.431, p  < 0.0001). G8 score and tumor burden are significant predictors of efficacy of antibiotic prophylaxis among older adults receiving chemoradiation. In older patients having poor G8 scores and advanced tumors, antibiotic prophylaxis is unsuitable. Interestingly, co-morbidities and poor performance status did not impact efficacy of antibiotic prophylaxis among our elderly patients.

Antibiotic Rotation for Febrile Neutropenic Patients with Hematological Malignancies: Clinical Significance of Antibiotic Heterogeneity

PubMed Central

Chong, Yong; Shimoda, Shinji; Yakushiji, Hiroko; Ito, Yoshikiyo; Miyamoto, Toshihiro; Kamimura, Tomohiko; Shimono, Nobuyuki; Akashi, Koichi

2013-01-01

Background Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance. Methods This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis. Results In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods. Conclusions We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia. PMID:23372683

Efficacy of granulocyte colony stimulating factor as a secondary prophylaxis along with full-dose chemotherapy following a prior cycle of febrile neutropenia.

PubMed

Gupta, Seema; Singh, Pankaj K; Bhatt, Madan L B; Pant, Mohan C; Gupta, Rajeev; Negi, Mahendra P S

2010-10-01

Secondary prophylaxis with recombinant human granulocyte colony stimulating factor (G-CSF) is recommended where patients have experienced febrile neutropenia in an earlier chemotherapy cycle and for whom the maintenance of chemotherapy dose intensity is important; or where febrile neutropenia has not occurred but prolonged neutropenia is causing excessive dose delay or reduction, where maintenance of dose intensity is important. The objective of this study was to determine the efficacy and feasibility of G-CSF as secondary prophylaxis when used along with full dose moderately myelotoxic chemotherapy following a prior cycle with febrile-neutropenia. Fifty-two patients aged 22-75 years with febrile neutropenia that required intravenous antibiotics following moderately myelotoxic chemotherapy were included. These patients received the next cycle of the same chemotherapy regime without dose modification but with support of filgrastim 24 h after completion of chemotherapy (300 μg/day/subcutaneously (s.c.) for weight < 60 kg, 480 μg/day/s.c. for weight > 60 kg, for at least 10 consecutive days), patients in whom neutropenia was associated with a life-threatening infection and those who developed prolonged myelosuppression were excluded. The use of the hematopoietic growth factor G-CSF was shown to shorten the neutrophil recovery time, resulting in significant reduction of incidence of febrile neutropenia, hospitalization and use of broad spectrum antibiotics. There was no drug related death or adverse events associated with either cycle. In conclusion, recombinant human G-CSF is effective and relatively safe as a secondary prophylaxis with full dose chemotherapy in patients who develop febrile neutropenia following prior cycles of moderately myelotoxic chemotherapy.

[Strategies of treatment for febrile neutropenia].

PubMed

Terui, Yasuhito

2013-06-01

The guideline on febrile neutropenia(FN)was published by the Japanese Society of Medical Oncology(JSMO)in 2012. Based on this guideline, the treatment strategy for febrile neutropenia that is discussed in this paper includes empiric treatment strategies, methicillin-resistant Staphylococcus aureus antibiotics in the initial treatment, treatment for severe FN, treatment for outpatients, duration of FN treatment, treatment after recovery from fever associated with neutropenia, and empiric treatment with anti-fungal drugs in patients with prolonged FN.

Oropouche fever epidemic in Northern Brazil: epidemiology and molecular characterization of isolates.

PubMed

Vasconcelos, Helena B; Azevedo, Raimunda S S; Casseb, Samir M; Nunes-Neto, Joaquim P; Chiang, Jannifer O; Cantuária, Patrick C; Segura, Maria N O; Martins, Lívia C; Monteiro, Hamilton A O; Rodrigues, Sueli G; Nunes, Márcio R T; Vasconcelos, Pedro F C

2009-02-01

Oropouche fever virus is an important arbovirus associated with febrile disease that re-emerged in 2006 in several municipalities of Pará State, Bragantina region, Amazon, Brazil, 26 years after the last epidemic. To investigate an Oropouche fever outbreak in this region. A serologic survey and prospective study of acute febrile cases were performed in Magalhães Barata (urban and rural areas) and Maracanã (rural area) municipalities. Serology (IgM-ELISA and hemagglutination-inhibition [HI]), virus isolation, RT-PCR and real-time-PCR were used to confirm Oropouche virus (OROV) as responsible for the febrile outbreaks. Real-time-PCR showed high titers of OROV in acute-phase serum samples from febrile patients. From 113 of 119 acutely febrile patients with paired serum samples, OROV infections was confirmed by serologic conversion (n=76) or high titers (n=37) for both HI and IgM-ELISA. Patients had a febrile disease characterized by headache, chills, dizziness, photophobia, myalgia, nausea, and vomiting. Females and children under 15 years of age were most affected. Nucleotide sequencing of six OROV isolates identified that genotype II was associated with the human disease epidemic. Oropouche fever, which has re-emerged in the Bragantina region in eastern Amazon 26 years after the last epidemic, is caused by genotype II, a lineage previously found only in Peru and western Brazil.

Febrile neutropenic infection occurred in cancer patients undergoing autologous peripheral blood stem cell transplantation.

PubMed

Zhang, W-X; Zhao, Q-Y; Huang, H-Q

2015-03-01

The objective of this study was to investigate the incidence, risk factors, and clinical and prognostic characteristics of febrile infection that occurred during the neutropenic period in cancer patients who underwent autologous peripheral blood stem cell transplantation (APBSCT). Clinical data of all the APBSCT cases from 2007 to 2009 in Sun Yat-sen University Cancer Center were collected and retrospectively analyzed. Eighty-nine APBSCT subjects were investigated. Neutropenia usually occurred on the 4th day (range, 0-15) after transplantation and lasted 6 (range, 3-27) days. Febrile neutropenia occurred in 78.7% patients and lasted around 3 (range, 1-20) days and no infection-related deaths were observed. For febrile episodes, 12 patients (17.1%) were diagnosed as having microbiologically documented infections (MDI). Initial empirical antimicrobial therapy was given to all cases of post-APBSCT febrile neutropenia, of which 44 cases (62.9%) were effective. Febrile neutropenia occurred in 25/34 (73.5%) patients who were given antifungal drugs for prophylaxis. Neutropenic infection is still the major complication in APBSCT patients and duration of neutropenia is one of the major risk factors. Prophylactic administration of antifungal drugs seems to be invalid to reduce post-APBSCT infection. Sufficient doses of broad-spectrum antibiotics at the early stage lead to better results of initial antimicrobial treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

LH750 hematology analyzers to identify malaria and dengue and distinguish them from other febrile illnesses.

PubMed

Sharma, P; Bhargava, M; Sukhachev, D; Datta, S; Wattal, C

2014-02-01

Tropical febrile illnesses such as malaria and dengue are challenging to differentiate clinically. Automated cellular indices from hematology analyzers may afford a preliminary rapid distinction. Blood count and VCS parameters from 114 malaria patients, 105 dengue patients, and 105 febrile controls without dengue or malaria were analyzed. Statistical discriminant functions were generated, and their diagnostic performances were assessed by ROC curve analysis. Three statistical functions were generated: (i) malaria-vs.-controls factor incorporating platelet count and standard deviations of lymphocyte volume and conductivity that identified malaria with 90.4% sensitivity, 88.6% specificity; (ii) dengue-vs.-controls factor incorporating platelet count, lymphocyte percentage and standard deviation of lymphocyte conductivity that identified dengue with 81.0% sensitivity and 77.1% specificity; and (iii) febrile-controls-vs.-malaria/dengue factor incorporating mean corpuscular hemoglobin concentration, neutrophil percentage, mean lymphocyte and monocyte volumes, and standard deviation of monocyte volume that distinguished malaria and dengue from other febrile illnesses with 85.1% sensitivity and 91.4% specificity. Leukocyte abnormalities quantitated by automated analyzers successfully identified malaria and dengue and distinguished them from other fevers. These economic discriminant functions can be rapidly calculated by analyzer software programs to generate electronic flags to trigger-specific testing. They could potentially transform diagnostic approaches to tropical febrile illnesses in cost-constrained settings. © 2013 John Wiley & Sons Ltd.

IL-8 predicts pediatric oncology patients with febrile neutropenia at low risk for bacteremia.

PubMed

Cost, Carrye R; Stegner, Martha M; Leonard, David; Leavey, Patrick

2013-04-01

Despite a low bacteremia rate, pediatric oncology patients are frequently admitted for febrile neutropenia. A pediatric risk prediction model with high sensitivity to identify patients at low risk for bacteremia is not available. We performed a single-institution prospective cohort study of pediatric oncology patients with febrile neutropenia to create a risk prediction model using clinical factors, respiratory viral infection, and cytokine expression. Pediatric oncology patients with febrile neutropenia were enrolled between March 30, 2010 and April 1, 2011 and managed per institutional protocol. Blood samples for C-reactive protein and cytokine expression and nasopharyngeal swabs for respiratory viral testing were obtained. Medical records were reviewed for clinical data. Statistical analysis utilized mixed multiple logistic regression modeling. During the 12-month period, 195 febrile neutropenia episodes were enrolled. There were 24 (12%) episodes of bacteremia. Univariate analysis revealed several factors predictive for bacteremia, and interleukin (IL)-8 was the most predictive variable in the multivariate stepwise logistic regression. Low serum IL-8 predicted patients at low risk for bacteremia with a sensitivity of 0.9 and negative predictive value of 0.98. IL-8 is a highly sensitive predictor for patients at low risk for bacteremia. IL-8 should be utilized in a multi-institution prospective trial to assign risk stratification to pediatric patients admitted with febrile neutropenia.

Clinical factors predicting bacteremia in low-risk febrile neutropenia after anti-cancer chemotherapy.

PubMed

Ha, Young Eun; Song, Jae-Hoon; Kang, Won Ki; Peck, Kyong Ran; Chung, Doo Ryeon; Kang, Cheol-In; Joung, Mi-Kyong; Joo, Eun-Jeong; Shon, Kyung Mok

2011-11-01

Bacteremia is an important clinical condition in febrile neutropenia that can cause clinical failure of antimicrobial therapy. The purpose of this study was to investigate the clinical factors predictive of bacteremia in low-risk febrile neutropenia at initial patient evaluation. We performed a retrospective cohort study in a university hospital in Seoul, Korea, between May 1995 and May 2007. Patients who met the criteria of low-risk febrile neutropenia at the time of visit to emergency department after anti-cancer chemotherapy were included in the analysis. During the study period, 102 episodes of bacteremia were documented among the 993 episodes of low-risk febrile neutropenia. Single gram-negative bacteremia was most frequent. In multivariate regression analysis, initial body temperature ≥39°C, initial hypotension, presence of clinical sites of infection, presence of central venous catheter, initial absolute neutrophil count <50/mm(3), and the CRP ≥10 mg/dL were statistically significant predictors for bacteremia. A scoring system using these variables was derived and the likelihood of bacteremia was well correlated with the score points with AUC under ROC curve of 0.785. Patients with low score points had low rate of bacteremia, thus, would be candidates for outpatient-based or oral antibiotic therapy. We identified major clinical factors that can predict bacteremia in low-risk febrile neutropenia.

Parental perspectives on inpatient versus outpatient management of pediatric febrile neutropenia.

PubMed

Diorio, Caroline; Martino, Julia; Boydell, Katherine Mary; Ethier, Marie-Chantal; Mayo, Chris; Wing, Richard; Teuffel, Oliver; Sung, Lillian; Tomlinson, Deborah

2011-01-01

To describe parent preference for treatment of febrile neutropenia and the key drivers of parental decision making, structured face-to-face interviews were used to elicit parent preferences for inpatient versus outpatient management of pediatric febrile neutropenia. Parents were presented with 4 different scenarios and asked to indicate which treatment option they preferred and to describe reasons for this preference during the face-to-face interview. Comments were recorded in writing by research assistants. A consensus approach to thematic analysis was used to identify themes from the written comments of the research assistants. A total of 155 parents participated in the study. Of these, 80 (51.6%) parents identified hospital-based intravenous treatment as the most preferred treatment scenario for febrile neutropenia. The major themes identified included convenience/disruptiveness, physical health, emotional well-being, and modifiers of parental decision making. Most parents preferred hospital-based treatment for febrile neutropenia. An understanding of issues that influence parental decision making may assist health care workers in planning program implementation and further support families in their decision-making process.

GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy.

PubMed

Koyama, Ryuta; Tao, Kentaro; Sasaki, Takuya; Ichikawa, Junya; Miyamoto, Daisuke; Muramatsu, Rieko; Matsuki, Norio; Ikegaya, Yuji

2012-08-01

Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ectopia that persists into adulthood. Febrile seizures induced an upregulation of GABA(A) receptors (GABA(A)-Rs) in neonatally generated granule cells, and hyperactivation of excitatory GABA(A)-Rs caused a reversal in the direction of granule cell migration. This abnormal migration was prevented by RNAi-mediated knockdown of the Na(+)K(+)2Cl(-) co-transporter (NKCC1), which regulates the excitatory action of GABA. NKCC1 inhibition with bumetanide after febrile seizures rescued the granule cell ectopia, susceptibility to limbic seizures and development of epilepsy. Thus, this work identifies a previously unknown pathogenic role of excitatory GABA(A)-R signaling and highlights NKCC1 as a potential therapeutic target for preventing granule cell ectopia and the development of epilepsy after febrile seizures.

Bacterial lung sepsis in patients with febrile neutropenia.

PubMed

Lanoix, Jean-Philippe; Schmit, Jean-Luc; Douadi, Youcef

2012-05-01

This review provides an update on microbiological and therapeutic data in febrile neutropenic patients in general and those with bacterial lung sepsis in particular. Although the Infectious Diseases Society of America updated its guidelines on febrile neutropenia in 2010, changing epidemiological factors and the spread of new drug resistance constitutes challenges for initial treatment of this condition. Lung sepsis stands out because of the frequent absence of microbiological identification. We review the use of newly available, novel, broad-spectrum antibiotics (linezolid, tigecycline, daptomycin, etc.) in this indication. Although the incidence of Gram-negative infections in neutropenic fever is leveling off, there is a worrying increase in resistance. New drugs are available but not well studied in febrile neutropenia; daptomycin and tigecycline should not be used in suspected lung sepsis in these patients. New diagnostic tools (such as the procalcitonin assay and the LightCycler SeptiFast assay, Roche Molecular Systems) appear to be unhelpful in febrile neutropenia, although more data on fungal sepsis are required. There are no specific features of the treatment of pneumonia or septic shock in neutropenic fever, but both conditions increase the mortality rate.

Atypical febrile seizures, mesial temporal lobe epilepsy, and dual pathology.

PubMed

Sanon, Nathalie T; Desgent, Sébastien; Carmant, Lionel

2012-01-01

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE.

Pleiotropic roles of Clostridium difficile sin locus

PubMed Central

Ou, Junjun; Dupuy, Bruno

2018-01-01

Clostridium difficile is the primary cause of nosocomial diarrhea and pseudomembranous colitis. It produces dormant spores, which serve as an infectious vehicle responsible for transmission of the disease and persistence of the organism in the environment. In Bacillus subtilis, the sin locus coding SinR (113 aa) and SinI (57 aa) is responsible for sporulation inhibition. In B. subtilis, SinR mainly acts as a repressor of its target genes to control sporulation, biofilm formation, and autolysis. SinI is an inhibitor of SinR, so their interaction determines whether SinR can inhibit its target gene expression. The C. difficile genome carries two sinR homologs in the operon that we named sinR and sinR’, coding for SinR (112 aa) and SinR’ (105 aa), respectively. In this study, we constructed and characterized sin locus mutants in two different C. difficile strains R20291 and JIR8094, to decipher the locus’s role in C. difficile physiology. Transcriptome analysis of the sinRR’ mutants revealed their pleiotropic roles in controlling several pathways including sporulation, toxin production, and motility in C. difficile. Through various genetic and biochemical experiments, we have shown that SinR can regulate transcription of key regulators in these pathways, which includes sigD, spo0A, and codY. We have found that SinR’ acts as an antagonist to SinR by blocking its repressor activity. Using a hamster model, we have also demonstrated that the sin locus is needed for successful C. difficile infection. This study reveals the sin locus as a central link that connects the gene regulatory networks of sporulation, toxin production, and motility; three key pathways that are important for C. difficile pathogenesis. PMID:29529083

Dengue and Other Common Causes of Acute Febrile Illness in Asia: An Active Surveillance Study in Children

PubMed Central

Capeding, Maria Rosario; Chua, Mary Noreen; Hadinegoro, Sri Rezeki; Hussain, Ismail I. H. M.; Nallusamy, Revathy; Pitisuttithum, Punnee; Rusmil, Kusnandi; Thisyakorn, Usa; Thomas, Stephen J.; Huu Tran, Ngoc; Wirawan, Dewa Nyoman; Yoon, In-Kyu; Bouckenooghe, Alain; Hutagalung, Yanee; Laot, Thelma; Wartel, Tram Anh

2013-01-01

Background Common causes of acute febrile illness in tropical countries have similar symptoms, which often mimic those of dengue. Accurate clinical diagnosis can be difficult without laboratory confirmation and disease burden is generally under-reported. Accurate, population-based, laboratory-confirmed incidence data on dengue and other causes of acute fever in dengue-endemic Asian countries are needed. Methods and principal findings This prospective, multicenter, active fever surveillance, cohort study was conducted in selected centers in Indonesia, Malaysia, Philippines, Thailand and Vietnam to determine the incidence density of acute febrile episodes (≥38°C for ≥2 days) in 1,500 healthy children aged 2–14 years, followed for a mean 237 days. Causes of fever were assessed by testing acute and convalescent sera from febrile participants for dengue, chikungunya, hepatitis A, influenza A, leptospirosis, rickettsia, and Salmonella Typhi. Overall, 289 participants had acute fever, an incidence density of 33.6 per 100 person-years (95% CI: 30.0; 37.8); 57% were IgM-positive for at least one of these diseases. The most common causes of fever by IgM ELISA were chikungunya (in 35.0% of in febrile participants) and S. Typhi (in 29.4%). The overall incidence density of dengue per 100 person-years was 3.4 by nonstructural protein 1 (NS1) antigen positivity (95% CI: 2.4; 4.8) and 7.3 (95% CI: 5.7; 9.2) by serology. Dengue was diagnosed in 11.4% (95% CI: 8.0; 15.7) and 23.9% (95% CI: 19.1; 29.2) of febrile participants by NS1 positivity and serology, respectively. Of the febrile episodes not clinically diagnosed as dengue, 5.3% were dengue-positive by NS1 antigen testing and 16.0% were dengue-positive by serology. Conclusions During the study period, the most common identified causes of pediatric acute febrile illness among the seven tested for were chikungunya, S. Typhi and dengue. Not all dengue cases were clinically diagnosed; laboratory confirmation is essential to refine disease burden estimates. PMID:23936565

Diagnostic value of sTREM-1, IL-8, PCT, and CRP in febrile neutropenia after autologous stem cell transplantation.

PubMed

Michel, C S; Teschner, D; Wagner, E M; Theobald, M; Radsak, Markus P

2017-12-01

Infections and infectious complications are the major cause of morbidity and mortality in febrile neutropenic patients after autologous stem cell transplantation. Laboratory biomarkers are helpful for early identification of critically ill patients and optimal therapy management. Several studies in adult non-neutropenic patients proposed sTREM-1 as a superior biomarker for identification of septic patients as well as a predictor for survival in these patients compared with procalcitonin (PCT), C-reactive protein (CRP), or interleukin-8 (IL-8). Here, to assess the utility of PCT, CRP, IL-8, and sTREM-1 in febrile neutropenia, 44 patients presenting with febrile neutropenia after autologous stem cell transplantation were recruited in a single-center prospective pilot study. We analyzed PCT and CRP as well as IL-8 and sTREM-1 levels pre- and post-transplantation at defined time points. In 20 of 44 patients, concentration of sTREM-1 was under the detection level at appearance of febrile neutropenia. Mean levels of PCT, IL-8, and CRP were significantly increased in infections of critically ill patients who by dysfunction or failure of one or more organs/system depend on survival from advanced instruments of monitoring and therapy. However, all tested biomarkers could not distinguish between presence and absence of bloodstream infection. The combination of the biomarkers PCT and IL-8 achieved a high sensitivity of 90% and specificity of 74% for the identification of serious complications in febrile neutropenia, whereas the combination of CRP and PCT or IL-8 achieved a high sensitivity of 100%, but with the addition of a low specificity of 47or 41%. In conclusion, we found that the measurement of sTREM-1 concentration at presentation of febrile neutropenia is not useful to identify bacterial bloodstream infections and critically ill patients. PCT and IL-8 are useful biomarkers for the early identification of critically ill patients, compared to CRP and sTREM-1 in febrile neutropenia. PCT or IL-8 in combination with clinical parameters should be considered in routine measurement to identify critically ill patients as early as possible.

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

PubMed

Lote, H; Sharp, A; Redana, S; Papadimitraki, E; Capelan, M; Ring, A

2016-09-01

Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower rates of febrile neutropenia than in other groups and may indicate relative under-dosing of chemotherapy. This supports international guidelines that state that obese patients should not be dose capped. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Atypical Febrile Seizures, Mesial Temporal Lobe Epilepsy, and Dual Pathology

PubMed Central

Sanon, Nathalie T.; Desgent, Sébastien; Carmant, Lionel

2012-01-01

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE. PMID:22957226

Febrile neutropenia and refeeding syndrome.

PubMed

Jahn, H K; Barraclough, S; Currell, S; Tighe, M P

2016-12-01

We describe the management of a 4-year-old child with acute lymphoblastic leukaemia (ALL) who presented with febrile neutropenia, Cryptosporidium and subsequently developed refeeding syndrome. Febrile neutropenia is common and can be life-threatening and we highlight the identification of well low-risk neutropenic children with resolved febrile illnesses suitable for early discharge. We also discuss the potential management strategies for Cryptosporidium Refeeding syndrome is not common, but should be considered as a cause of acute inpatient deterioration and is a significant risk, with potential morbidity, in children who have undergone a period of catabolism. This article reviews the current literature and provides useful guidance on these issues. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Impact of Middle East respiratory syndrome outbreak on the use of emergency medical resources in febrile patients.

PubMed

Jeong, Hyunho; Jeong, Sikyoung; Oh, Juseok; Woo, Seon Hee; So, Byung Hak; Wee, Jeong Hee; Kim, Ji Hoon; Im, Ji Yong; Choi, Seung Pill; Park, Kyoungnam; Cho, Byul Nim Hee; Hong, Sungyoup

2017-06-01

Outbreaks of transmissible respiratory infection are suspected to have significant effects on the health of pediatric and geriatric patients. The objective was to assess the impact of the Middle East respiratory syndrome (MERS) outbreak on the use of emergency resources. An ecologic analysis of emergency department (ED) records between September and December 2015, was performed. Data was obtained from the National Emergency Department Information System database for Korea. All demographic and diagnostic data from patients presenting with febrile symptoms as a main complaint were collected. The data were compared to the equivalent period in the three years preceding the MERS outbreak in Korea. Following the MERS outbreak, there was an increase in overall ED visits by febrile patients and the proportion of visits by febrile patients, relative to total ED attendances. This effect was more prominent in the children under five years. The duration of the chief complaint before ED arrival and the length of ED stay were significantly increased among younger pediatric patients. Decreased body temperature on arrival was observed in younger pediatric patients. MERS outbreak appears to have had a significant effects on ED use by febrile patients. The use of emergency care services by pediatric patients makes them more vulnerable to an outbreak of a transmissable disease. An effective strategy to control emergency center visits by non-urgent febrile patients and provide proper medical services is urgently needed.

Evidence on the use of paracetamol in febrile children.

PubMed Central

Russell, Fiona M.; Shann, Frank; Curtis, Nigel; Mulholland, Kim

2003-01-01

Antipyretics, including acetaminophen (paracetamol), are prescribed commonly in children with pyrexia, despite minimal evidence of a clinical benefit. A literature review was performed by searching Medline and the Cochrane databases for research papers on the efficacy of paracetamol in febrile illnesses in children and adverse outcomes related to the use of paracetamol. No studies showed any clear benefit for the use of paracetamol in therapeutic doses in febrile children with viral or bacterial infections or with malaria. Some studies suggested that fever may have a beneficial role in infection, although no definitive prospective studies in children have been done to prove this. The use of paracetamol in therapeutic doses generally is safe, although hepatotoxicity has occurred with recommended dosages in children. In developing countries where malnutrition is common, data on the safety of paracetamol are lacking. The cost of paracetamol for poor families is substantial. No evidence shows that it is beneficial to treat febrile children with paracetamol. Treatment should be given only to children who are in obvious discomfort and those with conditions known to be painful. The role of paracetamol in children with severe malaria or sepsis and in malnourished, febrile children needs to be clarified. PMID:12856055

Risk factors for febrile neutropenia during chemotherapy for HIV-related lymphoma.

PubMed

Park, Jinyong; Kim, Tae Min; Hwang, Jeong-Hwan; Kim, Nak-Hyun; Choe, Pyoeng Gyun; Song, Kyoung-ho; Kim, Eu Suk; Park, Sang-Won; Kim, Hong Bin; Kim, Nam Joong; Park, Wan Beom; Oh, Myoung-don

2012-12-01

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38℃; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma.

Risk Factors for Febrile Neutropenia during Chemotherapy for HIV-Related Lymphoma

PubMed Central

Park, Jinyong; Kim, Tae Min; Hwang, Jeong-Hwan; Kim, Nak-Hyun; Choe, Pyoeng Gyun; Song, Kyoung-ho; Kim, Eu Suk; Park, Sang-Won; Kim, Hong Bin; Kim, Nam Joong; Oh, Myoung-don

2012-01-01

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38℃; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma. PMID:23255844

Predictive factors for poor prognosis febrile neutropenia.

PubMed

Ahn, Shin; Lee, Yoon-Seon

2012-07-01

Most patients with chemotherapy-induced febrile neutropenia recover rapidly without serious complications. However, it still remains a life-threatening treatment-related toxicity, and is associated with dose reductions and delays of chemotherapeutic agents that may compromise treatment outcomes. Recent developments of risk stratification enabled early discharge with oral antibiotics for low-risk patients. However, even in low-risk patients, medical complications including bacteremia could happen. The authors reviewed recent literature to provide an update on research regarding predictive factors for poor prognosis in patients with febrile neutropenia. Various prognostic factors have been suggested with controversies. Hematological parameters, prophylactic measurements and patient-specific risk factors showed inconsistent results. MASCC risk-index score, which was originally developed to identify low-risk patients, in turn showed that the lower the MASCC score, the poorer the prognosis of febrile neutropenia, with very low levels (<15), the rate of complications was high. Patients with severe sepsis and septic shock commonly had procalcitonin concentration above 2.0 ng/ml, and this level should be considered at high risk of poor prognosis. Lower MASCC score and higher procalcitonin concentration can predict poor outcomes in febrile neutropenia. More research is required with regard to the other factors showing controversies.

Advances in management of low-risk febrile neutropenia.

PubMed

Teuffel, Oliver; Sung, Lillian

2012-02-01

To describe and discuss the most recent advances in the management of low-risk febrile neutropenia in children with cancer. Several risk stratification tools for children with febrile neutropenia have been developed, although none of these tools have been directly compared and few have been validated in independent populations. However, there is good evidence that, for pediatric patients with febrile neutropenia at low risk for severe infection, outpatient management is a well tolerated and efficacious alternative to inpatient care. Moreover, major progress has been made in obtaining and understanding perceived quality of life and preferences for outpatient management in pediatric cancer patients. Many parents prefer inpatient management although child quality of life is, in general, anticipated to be higher with outpatient intravenous therapy. Finally, outpatient strategies are more cost-effective as compared with traditional management in hospital. Outpatient management is a well tolerated and cost-effective strategy for low-risk febrile neutropenia in children with cancer, although parental preferences are highly variable for outpatient versus inpatient management. Future research should examine the effectiveness of outpatient strategies through conduct of large cohort studies. Other future work could focus on development of decision aids and other tools to facilitate ambulatory approaches.

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.

Dual Regulation of Bacillus subtilis kinB Gene Encoding a Sporulation Trigger by SinR through Transcription Repression and Positive Stringent Transcription Control.

PubMed

Fujita, Yasutaro; Ogura, Mitsuo; Nii, Satomi; Hirooka, Kazutake

2017-01-01

It is known that transcription of kinB encoding a trigger for Bacillus subtilis sporulation is under repression by SinR, a master repressor of biofilm formation, and under positive stringent transcription control depending on the adenine species at the transcription initiation nucleotide (nt). Deletion and base substitution analyses of the kinB promoter (P kinB ) region using lacZ fusions indicated that either a 5-nt deletion (Δ5, nt -61/-57, +1 is the transcription initiation nt) or the substitution of G at nt -45 with A (G-45A) relieved kinB repression. Thus, we found a pair of SinR-binding consensus sequences (GTTCTYT; Y is T or C) in an inverted orientation (SinR-1) between nt -57/-42, which is most likely a SinR-binding site for kinB repression. This relief from SinR repression likely requires SinI, an antagonist of SinR. Surprisingly, we found that SinR is essential for positive stringent transcription control of P kinB . Electrophoretic mobility shift assay (EMSA) analysis indicated that SinR bound not only to SinR-1 but also to SinR-2 (nt -29/-8) consisting of another pair of SinR consensus sequences in a tandem repeat arrangement; the two sequences partially overlap the '-35' and '-10' regions of P kinB . Introduction of base substitutions (T-27C C-26T) in the upstream consensus sequence of SinR-2 affected positive stringent transcription control of P kinB , suggesting that SinR binding to SinR-2 likely causes this positive control. EMSA also implied that RNA polymerase and SinR are possibly bound together to SinR-2 to form a transcription initiation complex for kinB transcription. Thus, it was suggested in this work that derepression of kinB from SinR repression by SinI induced by Spo0A∼P and occurrence of SinR-dependent positive stringent transcription control of kinB might induce effective sporulation cooperatively, implying an intimate interplay by stringent response, sporulation, and biofilm formation.

Cerebrospinal fluid acid-base status and lactate and pyruvate concentrations after short (less than 30 minutes) first febrile convulsions in children.

PubMed Central

Simpson, H; Habel, A H; George, E L

1977-01-01

Twenty-nine infants and children with short (less than 30 minutes) first febrile convulsions were studied between 3 and 22 hours after convulsive episodes. Arterial and CSF acid-base variables, lactate and pyruvate concentrations, and lactate/pyruvate ratios were measured. Biochemical signs of cerebral hypoxia were found in only 2 patients, one of whom had short, repeated convulsions. Our findings indicate that hypoxic damage is unlikely to result from a short-duration febrile convulsion. PMID:23077

When to perform urine cultures in respiratory syncytial virus-positive febrile older infants?

PubMed

Kaluarachchi, Dinushan; Kaldas, Virginia; Erickson, Evelyn; Nunez, Randolph; Mendez, Magda

2014-09-01

Respiratory syncytial virus (RSV) infections are associated with clinically significant rate of urinary tract infections (UTIs) in young infants. Previous research investigating RSV infections and UTIs has been performed mainly in infants younger than 2 to 3 months and has not focused on the risk of UTI in infants 3 to 12 months. This study aimed to assess the rate of UTIs in febrile RSV-positive older infants admitted as inpatients and identify predictors of UTI in febrile RSV-positive older infants. This is a retrospective comparative study of febrile RSV-positive infants 0 to 12 months of age admitted to the inpatient pediatric unit of Lincoln Medical and Mental Health Center, Bronx, from September through April 2006 to 2012. Infants 3 to 12 months were considered the cases, and infants 0 to 3 months were the comparative group. The rate of UTIs between the 2 groups was compared. Univariate tests and multiple logistic regression were used to identify demographic/clinical factors associated with UTI in febrile RSV-positive older infants. A total of 414 RSV-positive febrile infants were enrolled including 297 infants 3 to 12 months of age. The rate of UTI in older infants was 6.1% compared with 6.8% in infants younger than 3 months. Positive urinalysis finding was an independent predictor of UTI (P = 0.003) in older infants. All 11 boys with UTI were uncircumcised, and none of the 51 circumcised boys had UTI. Demographic (race, sex, and age) and clinical factors (temperature, white blood cell count, and absolute neutrophil count) were not associated with UTI. Febrile older infants who are RSV positive have a clinically significant rate of UTIs. It seems prudent to examine the urine of these older infants. Positive urinalysis finding was a predictive factor of UTI. Circumcised boys are at a decreased risk of UTI, compared with uncircumcised boys.

Distal Ureteral Diameter Ratio is Predictive of Breakthrough Febrile Urinary Tract Infection.

PubMed

Arlen, Angela M; Leong, Traci; Guidos, P Joseph; Alexander, Siobhan E; Cooper, Christopher S

2017-12-01

Distal ureteral diameter ratio is an objective measure that is prognostic of spontaneous resolution of vesicoureteral reflux. Along with likelihood of resolution, improved identification of children at risk for recurrent febrile urinary tract infections may impact management decisions. We evaluated the usefulness of ureteral diameter ratio as a predictive factor for breakthrough febrile urinary tract infections. Children with primary vesicoureteral reflux and detailed voiding cystourethrogram were identified. Ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 and L3 vertebral bodies. Demographics, vesicoureteral reflux grade, laterality, presence/absence of bladder-bowel dysfunction, and ureteral diameter ratio were tested in univariate and multivariable analyses. Primary outcome was breakthrough febrile urinary tract infections. We analyzed 112 girls and 28 boys with a mean ± SD age of 2.5 ± 2.3 years at diagnosis. Vesicoureteral reflux was grade 1 to 2 in 64 patients (45.7%), grade 3 in 50 (35.7%), grade 4 in 16 (11.4%) and grade 5 in 10 (7.2%). Mean ± SD followup was 3.2 ± 2.7 years. A total of 40 children (28.6%) experienced breakthrough febrile urinary tract infections. Ureteral diameter ratio was significantly greater in children with (0.36) vs without (0.25) breakthrough febrile infections (p = 0.004). Controlling for vesicoureteral reflux grade, every 0.1 U increase in ureteral diameter ratio resulted in 1.7 times increased odds of breakthrough infection (95% CI 1.24 to 2.26, p <0.0001). Children with increased distal ureteral diameter ratio are at greater risk for breakthrough febrile urinary tract infections independent of reflux grade. Ureteral diameter ratio provides valuable prognostic information about risk of recurrent pyelonephritis and may assist with clinical decision-making. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Quest for certainty regarding early discharge in paediatric low-risk febrile neutropenia: a multicentre qualitative focus group discussion study involving patients, parents and healthcare professionals in the UK

PubMed Central

Phillips, Bob; Stewart, Lesley A; Atkin, Karl

2018-01-01

Objectives A systematic review of paediatric low-risk febrile neutropenia found that outpatient care is safe, with low rates of treatment failure. However, this review, and a subsequent meta-ethnography, suggested that early discharge of these patients may not be acceptable to key stakeholders. This study aimed to explore experiences and perceptions of patients, parents and healthcare professionals involved in paediatric febrile neutropenia care in the UK. Setting Three different centres within the UK, purposively selected from a national survey on the basis of differences in their service structure and febrile neutropenia management. Participants Thirty-two participants were included in eight focus group discussions. Primary outcomes Experiences and perceptions of paediatric febrile neutropenia care, including possible future reductions in therapy. Results Participants described a quest for certainty, in which they attempted to balance the uncertainty involved in understanding, expressing and negotiating risk with the illusion of certainty provided by strict protocols. Participants assessed risk using both formal and informal stratification tools, overlaid with emotional reactions to risk and experiences of risk within other situations. The benefits of certainty provided by protocols were counterbalanced by frustration at their strict constraints. The perceived benefits and harms of previous inpatient care informed participants’ appraisals of future treatment strategies. Conclusions This study highlighted the previously underestimated harms of admission for febrile neutropenia and the paternalistic nature of decision making, along with the frustrations and challenges for all parties involved in febrile neutropenia care. It demonstrates how the same statistics, generated by systematic reviews, can be used by key stakeholders to interpret risk differently, and how families in particular can view the harms of therapeutic options as different from the outcomes used within the literature. It justifies a reassessment of current treatment strategies for these children and further exploration of the potential to introduce shared decision making. PMID:29764879

Quaternary re-arrangement analysed by spectral enhancement: the interaction of a sporulation repressor with its antagonist.

PubMed

Scott, D J; Leejeerajumnean, S; Brannigan, J A; Lewis, R J; Wilkinson, A J; Hoggett, J G

1999-11-12

The protein/protein interaction between SinI and SinR has been studied by analytical ultracentrifugation and gel electrophoresis in an attempt to understand how these proteins contribute to developmental control of sporulation in Bacillus subtilis. SinR was found to be tetrameric, while SinI was found to exist as monomers and dimers in a rapidly reversible equilibrium. Labelling of SinR by incorporating the tryptophan analogue 7-azatryptophan (7AW) into the protein in place of tryptophan shifts the UV absorbance spectrum, thus allowing selective monitoring of 7AWSinR at 315 nm using the UV absorption optics of the analytical ultracentrifuge. Selective monitoring of SinR in mixtures of SinR and SinI enables the binding and stoichiometry of the interaction to be investigated quantitatively and unambiguously. We demonstrate that the oligomeric forms of SinR and SinI re-arrange to form a tight 1:1 SinR:SinI complex, with no stable intermediate species. A fragment of SinR, SinR(1-69), which contains only the DNA-binding domain, was found to be monomeric, showing that the protein appears not to oligomerise in a similar manner to the Cro repressor, a protein with which it shares a marked structural similarity. Copyright 1999 Academic Press.

A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots

PubMed Central

Bejon, Philip; Williams, Thomas N; Nyundo, Christopher; Hay, Simon I; Benz, David; Gething, Peter W; Otiende, Mark; Peshu, Judy; Bashraheil, Mahfudh; Greenhouse, Bryan; Bousema, Teun; Bauni, Evasius; Marsh, Kevin; Smith, David L; Borrmann, Steffen

2014-01-01

Malaria transmission is spatially heterogeneous. This reduces the efficacy of control strategies, but focusing control strategies on clusters or ‘hotspots’ of transmission may be highly effective. Among 1500 homesteads in coastal Kenya we calculated (a) the fraction of febrile children with positive malaria smears per homestead, and (b) the mean age of children with malaria per homestead. These two measures were inversely correlated, indicating that children in homesteads at higher transmission acquire immunity more rapidly. This inverse correlation increased gradually with increasing spatial scale of analysis, and hotspots of febrile malaria were identified at every scale. We found hotspots within hotspots, down to the level of an individual homestead. Febrile malaria hotspots were temporally unstable, but 4 km radius hotspots could be targeted for 1 month following 1 month periods of surveillance. DOI: http://dx.doi.org/10.7554/eLife.02130.001 PMID:24843017

Guaroa Virus Infection among Humans in Bolivia and Peru

PubMed Central

Aguilar, Patricia V.; Morrison, Amy C.; Rocha, Claudio; Watts, Douglas M.; Beingolea, Luis; Suarez, Victor; Vargas, Jorge; Cruz, Cristhopher; Guevara, Carolina; Montgomery, Joel M.; Tesh, Robert B.; Kochel, Tadeusz J.

2010-01-01

Guaroa virus (GROV) was first isolated from humans in Colombia in 1959. Subsequent isolates of the virus have been recovered from febrile patients and mosquitoes in Brazil, Colombia, and Panama; however, association of the virus with human disease has been unclear. As part of a study on the etiology of febrile illnesses in Peru and Bolivia, 14 GROV strains were isolated from patients with febrile illnesses, and 3 additional cases were confirmed by IgM seroconversion. The prevalence rate of GROV antibodies among Iquitos residents was 13%; the highest rates were among persons with occupations such as woodcutters, fisherman, and oil-field workers. Genetic characterization of representative GROV isolates indicated that strains from Peru and Bolivia form a monophyletic group that can be distinguished from strains isolated earlier in Brazil and Colombia. This study confirms GROV as a cause of febrile illness in tropical regions of Central and South America. PMID:20810845

A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots.

PubMed

Bejon, Philip; Williams, Thomas N; Nyundo, Christopher; Hay, Simon I; Benz, David; Gething, Peter W; Otiende, Mark; Peshu, Judy; Bashraheil, Mahfudh; Greenhouse, Bryan; Bousema, Teun; Bauni, Evasius; Marsh, Kevin; Smith, David L; Borrmann, Steffen

2014-04-24

Malaria transmission is spatially heterogeneous. This reduces the efficacy of control strategies, but focusing control strategies on clusters or 'hotspots' of transmission may be highly effective. Among 1500 homesteads in coastal Kenya we calculated (a) the fraction of febrile children with positive malaria smears per homestead, and (b) the mean age of children with malaria per homestead. These two measures were inversely correlated, indicating that children in homesteads at higher transmission acquire immunity more rapidly. This inverse correlation increased gradually with increasing spatial scale of analysis, and hotspots of febrile malaria were identified at every scale. We found hotspots within hotspots, down to the level of an individual homestead. Febrile malaria hotspots were temporally unstable, but 4 km radius hotspots could be targeted for 1 month following 1 month periods of surveillance.DOI: http://dx.doi.org/10.7554/eLife.02130.001. Copyright © 2014, Bejon et al.

Advances in the treatment of neutropenia.

PubMed

Dale, David C

2009-09-01

The present review updates treatment of neutropenia from articles published from January 2008 through April 2009. Chemotherapy-induced neutropenia occurs most commonly in the first cycle of treatment. Older patients, patients with multiple comorbidities, and those receiving more myelotoxic drugs are prone to develop neutropenia and its complications. Current guidelines recommend the prophylactic use of the myeloid growth factors for the first cycle of chemotherapy for patients with more than a 20% risk of febrile neutropenia. Meta analysis from randomized trials shows that granulocyte colony-stimulating factor prophylaxis is associated with patients receiving more intensive chemotherapy, having better survival, but also having a higher risk of secondary acute myeloid leukemia. Antibiotics are standard treatment of febrile neutropenia and are increasingly used for prophylaxis in 'low-risk' patients. The myeloid growth factor granulocyte colony-stimulating factor has radically changed our approach to the prevention of febrile neutropenia. Antibiotics remain the mainstay of treatment of febrile neutropenia.

Fever detection from free-text clinical records for biosurveillance.

PubMed

Chapman, Wendy W; Dowling, John N; Wagner, Michael M

2004-04-01

Automatic detection of cases of febrile illness may have potential for early detection of outbreaks of infectious disease either by identification of anomalous numbers of febrile illness or in concert with other information in diagnosing specific syndromes, such as febrile respiratory syndrome. At most institutions, febrile information is contained only in free-text clinical records. We compared the sensitivity and specificity of three fever detection algorithms for detecting fever from free-text. Keyword CC and CoCo classified patients based on triage chief complaints; Keyword HP classified patients based on dictated emergency department reports. Keyword HP was the most sensitive (sensitivity 0.98, specificity 0.89), and Keyword CC was the most specific (sensitivity 0.61, specificity 1.0). Because chief complaints are available sooner than emergency department reports, we suggest a combined application that classifies patients based on their chief complaint followed by classification based on their emergency department report, once the report becomes available.

Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B.

PubMed

Sun, Yuelian; Christensen, Jakob; Hviid, Anders; Li, Jiong; Vedsted, Peter; Olsen, Jørn; Vestergaard, Mogens

2012-02-22

Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. A population-based cohort study of 378,834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort. Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study. A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100,000 person-days), 32 children after the second (1.3 per 100,000 person-days), and 201 children after the third (8.5 per 100,000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100,000 person-days), 12 children after the second (5.7 per 100,000 person-days), and 27 children after the third (13.1 per 100,000 person-days) vaccinations. The relative incidences from the SCCS study design were similar to the cohort study design. Within 7 years of follow-up, 131 unvaccinated children and 2117 vaccinated children were diagnosed with epilepsy, 813 diagnosed between 3 and 15 months (2.4 per 1000 person-years) and 1304 diagnosed later in life (1.3 per 1000 person-years). After vaccination, children had a lower risk of epilepsy between 3 and 15 months (HR, 0.63; 95% CI, 0.50-0.79) and a similar risk for epilepsy later in life (HR, 1.01; 95% CI, 0.66-1.56) vs unvaccinated children. DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy.

Therapeutic burst-suppression coma in pediatric febrile refractory status epilepticus.

PubMed

Lin, Jainn-Jim; Chou, Cheng-Che; Lan, Shih-Yun; Hsiao, Hsiang-Ju; Wang, Yu; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Lin, Kuang-Lin

2017-09-01

Evidence for the beneficial effect of therapeutic burst-suppression coma in pediatric patients with febrile refractory status epilepticus is limited, and the clinical outcomes of this treatment strategy are largely unknown. Therefore, the aim of this study was to explore the outcomes of therapeutic burst-suppression coma in a series of children with febrile refractory status epilepticus. We retrospectively reviewed consecutive pediatric patients with febrile refractory status epilepticus admitted to our pediatric intensive care unit between January 2000 and December 2013. The clinical characteristics were analyzed. Thirty-five patients (23 boys; age range: 1-18years) were enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of the patients received the continuous administration of intravenous antiepileptic drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved therapeutic burst-suppression coma. All of the patients received mechanical ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%) patients died within 1month. The neurologically functional outcomes at 6months were good in six (27.3%) of the 22 survivors, of whom two returned to clinical baseline. The patients with therapeutic burst-suppression coma were significantly associated with hemodynamic support than the patients with electrographic seizures control (p=0.03), and had a trend of higher 1-month mortality rate, worse 6months outcomes, and a longer duration of hospitalization. Our results suggest that therapeutic burst-suppression coma to treat febrile refractory status epilepticus may lead to an increased risk of hemodynamic instability and a trend of worse outcomes. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Beliefs and expectations of Canadian parents who bring febrile children for medical care.

PubMed

Enarson, Mark C; Ali, Samina; Vandermeer, Ben; Wright, Robert B; Klassen, Terry P; Spiers, Judith A

2012-10-01

The purpose of this survey was to study the beliefs, expectations, and satisfaction of Canadian parents regarding fever and the treatment of their febrile children. A survey was developed exploring caregiver beliefs and treatment strategies, as well as expectations and satisfaction with medical care. Some items were modeled after previous studies to allow comparison. Caregivers with febrile children were recruited from 2005 to 2007 at 3 urgent care centers and emergency departments in Edmonton, Canada: a pediatric emergency department (n = 376), an urban urgent care center (n = 227), and a suburban urgent care clinic (n = 173). High and rapidly rising temperature, as well as physical symptoms associated with fever, caused concern in most parents surveyed. Seventy-four percent of parents felt that the elevated temperature from fever was dangerous and 90.3% always try to treat it. Forty degrees Celsius was the most commonly sited threshold for danger. Identifying the cause (80.6%) and seriousness (87.4%) of fever were the most com-mon stressors identified. Caregivers expected to receive information about the child's illness and appropriate treatment. The parents most often wanted information about febrile seizures and the potential dangers of febrile illness. Only 16.7% of caregivers expected anti-biotics. Nearly 92% of subjects were usually satisfied with medical care. Fever phobia continues to be a significant issue for Canadian parents. As a result, they treat fever aggressively and often seek medical attention. Good communication is important for medical staff caring for febrile children and typically leads to satisfied parents.

Influence of sex and age on febrile responses to peripheral and central administration of pyrogens in the rabbit

PubMed Central

Lipton, J. M.; Ticknor, C. B.

1979-01-01

1. Intravenous injections of leucocytic pyrogen in doses of 15, 30 and 60 μl./kg caused febrile reactions in male rabbits that were related to age of the animal: rabbits under 2 yr of age developed fevers that were related to dose of pyrogen, while rabbits 2-3 yr old showed large febrile responses which were not dose-related. 2. Female rabbits of comparable ages generally showed smaller febrile reactions to I.V. leucocytic pyrogen, and still older females (3-5 yr) developed fever only after the largest dose. 3. Dose-related febrile responses to 2·5, 5 and 10 μl. leucocytic pyrogen given intracerebroventricularly (I.C.V.) were greater in male rabbits 1-3 yr old than in females of comparable age. Female rabbits 3-5 yr old showed dose-related fevers that were smaller than those of younger animals of both sexes. 4. There were no major differences in response to 125, 250 and 500 ng PGE2, given I.C.V., between male and female rabbits under 2 yr of age. Females 2-3 yr of age had greater responses to PGE2 than males of comparable age whilst the oldest females showed smaller responses. 5. It is concluded that the febrile response of the rabbit to peripheral and central leucocytic pyrogen varies with both age and sex. Differences in sensitivity of central fever controls to endogenous pyrogen in animals of different ages and sexes may account for the different responses to peripheral pyrogen. PMID:521933

Influence of sex and age on febrile responses to peripheral and central administration of pyrogens in the rabbit.

PubMed

Lipton, J M; Ticknor, C B

1979-10-01

1. Intravenous injections of leucocytic pyrogen in doses of 15, 30 and 60 mul./kg caused febrile reactions in male rabbits that were related to age of the animal: rabbits under 2 yr of age developed fevers that were related to dose of pyrogen, while rabbits 2-3 yr old showed large febrile responses which were not dose-related.2. Female rabbits of comparable ages generally showed smaller febrile reactions to I.V. leucocytic pyrogen, and still older females (3-5 yr) developed fever only after the largest dose.3. Dose-related febrile responses to 2.5, 5 and 10 mul. leucocytic pyrogen given intracerebroventricularly (I.C.V.) were greater in male rabbits 1-3 yr old than in females of comparable age. Female rabbits 3-5 yr old showed dose-related fevers that were smaller than those of younger animals of both sexes.4. There were no major differences in response to 125, 250 and 500 ng PGE(2), given I.C.V., between male and female rabbits under 2 yr of age. Females 2-3 yr of age had greater responses to PGE(2) than males of comparable age whilst the oldest females showed smaller responses.5. It is concluded that the febrile response of the rabbit to peripheral and central leucocytic pyrogen varies with both age and sex. Differences in sensitivity of central fever controls to endogenous pyrogen in animals of different ages and sexes may account for the different responses to peripheral pyrogen.

Diagnostic Value of PCR Analysis of Bacteria and Fungi from Blood in Empiric-Therapy-Resistant Febrile Neutropenia ▿

PubMed Central

Nakamura, Akiko; Sugimoto, Yuka; Ohishi, Kohshi; Sugawara, Yumiko; Fujieda, Atsushi; Monma, Fumihiko; Suzuki, Kei; Masuya, Masahiro; Nakase, Kazunori; Matsushima, Yoshiko; Wada, Hideo; Katayama, Naoyuki; Nobori, Tsutomu

2010-01-01

This study aimed to assess the clinical utility of PCR for the analysis of bacteria and fungi from blood for the management of febrile neutropenic patients with hematologic malignancies. Using a PCR system able to detect a broad range of bacteria and fungi, we conducted a prospective pilot study of periodic analyses of blood from patients following intensive chemotherapy. When fever occurred, it was treated with empirical antibiotic therapy, basically without knowledge of the PCR results. In 23 febrile episodes during the neutropenic period, bacteria were detected by PCR in 11 cases, while the same species were identified by blood culture in 3 cases. In 10 out of 11 PCR-positive cases, fever could be managed by empirical therapy. In the empirical-therapy-resistant case, the identification of Stenotrophomonas maltophilia by PCR led to improvement of fever. No fungi were detected by PCR in febrile cases, while Aspergillus fumigatus was detected in one afebrile patient, several days before a clinical diagnosis was made. In subsequent sporadic PCR analyses in 15 cases of febrile neutropenia, bacteria were detected by both PCR and blood culture in 7 cases and by PCR alone in 6. Fungi were not detected. While fever was improved by empirical therapy in 12 out of the 13 PCR-positive cases, the identification of Pseudomonas aeruginosa by PCR in one therapy-resistant case contributed to the successful treatment of persistent fever. Our results indicate that PCR analysis of bacteria from blood provides essential information for managing empirical-therapy-resistant febrile neutropenia. PMID:20392911

Etiology of Severe Febrile Illness in Low- and Middle-Income Countries: A Systematic Review

PubMed Central

Prasad, Namrata; Murdoch, David R.; Reyburn, Hugh; Crump, John A.

2015-01-01

Background With apparent declines in malaria worldwide during the last decade and more widespread use of malaria rapid diagnostic tests, healthcare workers in low-resource areas face a growing proportion of febrile patients without malaria. We sought to describe current knowledge and identify information gaps of the etiology severe febrile illness in low-and middle-income countries. Methods and Findings We conducted a systematic review of studies conducted in low-and-middle income countries 1980–2013 that prospectively assessed consecutive febrile patients admitted to hospital using rigorous laboratory-based case definitions. We found 45 eligible studies describing 54,578 patients; 9,771 (17.9%) had a positive result for ≥1 pathogen meeting diagnostic criteria. There were no eligible studies identified from Southern and Middle Africa, Eastern Asia, Oceania, Latin American and Caribbean regions, and the European region. The median (range) number of diagnostic tests meeting our confirmed laboratory case definitions was 2 (1 to 11) per study. Of diagnostic tests, 5,052 (10.3%) of 49,143 had confirmed bacterial or fungal bloodstream infection; 709 (3.8%) of 18,142 had bacterial zoonosis; 3,488 (28.5%) of 12,245 had malaria; and 1,804 (17.4%) of 10,389 had a viral infection. Conclusions We demonstrate a wide range of pathogens associated with severe febrile illness and highlight the substantial information gaps regarding the geographic distribution and role of common pathogens. High quality severe febrile illness etiology research that is comprehensive with respect to pathogens and geographically representative is needed. PMID:26126200

Sin3b interacts with Myc and decreases Myc levels.

PubMed

Garcia-Sanz, Pablo; Quintanilla, Andrea; Lafita, M Carmen; Moreno-Bueno, Gema; García-Gutierrez, Lucia; Tabor, Vedrana; Varela, Ignacio; Shiio, Yuzuru; Larsson, Lars-Gunnar; Portillo, Francisco; Leon, Javier

2014-08-08

Myc expression is deregulated in many human cancers. A yeast two-hybrid screen has revealed that the transcriptional repressor Sin3b interacts with Myc protein. Endogenous Myc and Sin3b co-localize and interact in the nuclei of human and rat cells, as assessed by co-immunoprecipitation, immunofluorescence, and proximity ligation assay. The interaction is Max-independent. A conserved Myc region (amino acids 186-203) is required for the interaction with Sin3 proteins. Histone deacetylase 1 is recruited to Myc-Sin3b complexes, and its deacetylase activity is required for the effects of Sin3b on Myc. Myc and Sin3a/b co-occupied many sites on the chromatin of human leukemia cells, although the presence of Sin3 was not associated with gene down-regulation. In leukemia cells and fibroblasts, Sin3b silencing led to Myc up-regulation, whereas Sin3b overexpression induced Myc deacetylation and degradation. An analysis of Sin3b expression in breast tumors revealed an association between low Sin3b expression and disease progression. The data suggest that Sin3b decreases Myc protein levels upon Myc deacetylation. As Sin3b is also required for transcriptional repression by Mxd-Max complexes, our results suggest that, at least in some cell types, Sin3b limits Myc activity through two complementary activities: Mxd-dependent gene repression and reduction of Myc levels. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Febrile events including convulsions following the administration of four brands of 2010 and 2011 inactivated seasonal influenza vaccine in NZ infants and children: the importance of routine active safety surveillance.

PubMed

Petousis-Harris, Helen; Poole, Tracey; Turner, Nikki; Reynolds, Gary

2012-07-13

To evaluate and compare rates of febrile events, including febrile convulsion, following immunisation with four brands of inactivated 2010 and 2011 influenza vaccine in NZ infants and children. Retrospective telephone surveys of parents of infants and children who received at least one dose of the vaccines of interest. 184 NZ General Practices who received the vaccines of interest. Recipients of 4088 doses of trivalent inactivated vaccines Fluvax(®), Vaxigrip(®), Influvac(®) and Fluarix(®) and/or monovalent Celvapan. Vaccinees were identified via the electronic Practice Management System and contacted consecutively. Primary outcome was febrile convulsive seizure. Secondary outcomes were presence of fever plus other organ system specific symptoms. The parental response rate was 99%. Of 4088 doses given, 865 were Fluvax(®), 2571 Vaxigrip(®), 204 Influvac(®), 438 Fluarix(®) and 10 Celvapan. Three febrile convulsions followed Fluvax(®), a rate of 35 per 10,000 doses. No convulsions occurred following any dose of the other vaccines. There were nine febrile events that included rigors, all following Fluvax(®). Fever occurred significantly more frequently following administration of Fluvax(®) compared with the other brands of vaccines (p<0.0001) and Fluvax recipients were more likely to seek medical attention. Influvac(®) also had higher rates of febrile reactions (OR 0.54, 0.36-0.81) than the other two brands Vaxigrip(®) (OR 0.21, 0.16-0.27) and Fluarix(®) (OR 0.10, 0.05-0.20). After multivariable analysis vaccine, European ethnicity and second dose of vaccine were significantly associated with reporting of fever within 24h of vaccination. Influenza vaccines have different rates of reactogenicity in children which varies between ethnic groups. High rates of febrile convulsions and reactions in children receiving Fluvax(®) and to a lesser extent the higher fever rates in those receiving Influvac(®) compared with the other two brands of influenza vaccines in this study suggests that reactogenicity profiles need to be considered prior to national policy advice each season. The risk-benefit profile in children might not be equally favourable for all licensed paediatric influenza vaccines. More attention needs to be given to comparative research for all trivalent seasonal vaccines, and with all strain changes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger.

PubMed

Mahajan, Prashant; Kuppermann, Nathan; Mejias, Asuncion; Suarez, Nicolas; Chaussabel, Damien; Casper, T Charles; Smith, Bennett; Alpern, Elizabeth R; Anders, Jennifer; Atabaki, Shireen M; Bennett, Jonathan E; Blumberg, Stephen; Bonsu, Bema; Borgialli, Dominic; Brayer, Anne; Browne, Lorin; Cohen, Daniel M; Crain, Ellen F; Cruz, Andrea T; Dayan, Peter S; Gattu, Rajender; Greenberg, Richard; Hoyle, John D; Jaffe, David M; Levine, Deborah A; Lillis, Kathleen; Linakis, James G; Muenzer, Jared; Nigrovic, Lise E; Powell, Elizabeth C; Rogers, Alexander J; Roosevelt, Genie; Ruddy, Richard M; Saunders, Mary; Tunik, Michael G; Tzimenatos, Leah; Vitale, Melissa; Dean, J Michael; Ramilo, Octavio

Young febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns ("RNA biosignatures") in response to infections may provide an alternative diagnostic approach. To assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections. Prospective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature >38° C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type. RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections. Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores. Of 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections-including 32 with bacteremia and 15 with urinary tract infections-and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94% (95% CI, 70%-100%) sensitivity and 95% (95% CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43). In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with vs without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice.

Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger

PubMed Central

Mahajan, Prashant; Kuppermann, Nathan; Mejias, Asuncion; Suarez, Nicolas; Chaussabel, Damien; Casper, T. Charles; Smith, Bennett; Alpern, Elizabeth R.; Anders, Jennifer; Atabaki, Shireen M.; Bennett, Jonathan E.; Blumberg, Stephen; Bonsu, Bema; Borgialli, Dominic; Brayer, Anne; Browne, Lorin; Cohen, Daniel M.; Crain, Ellen F.; Cruz, Andrea T.; Dayan, Peter S.; Gattu, Rajender; Greenberg, Richard; Hoyle, John D.; Jaffe, David M.; Levine, Deborah A.; Lillis, Kathleen; Linakis, James G.; Muenzer, Jared; Nigrovic, Lise E.; Powell, Elizabeth C.; Rogers, Alexander J.; Roosevelt, Genie; Ruddy, Richard M.; Saunders, Mary; Tunik, Michael G.; Tzimenatos, Leah; Vitale, Melissa; Dean, J. Michael; Ramilo, Octavio

2016-01-01

IMPORTANCE Young febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns (“RNA biosignatures”) in response to infections may provide an alternative diagnostic approach. OBJECTIVE To assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections. DESIGN, SETTING, AND PARTICIPANTS Prospective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature >38° C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type. EXPOSURE RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections. MAIN OUTCOMES AND MEASURES Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores. RESULTS Of 1883 febrile infants (median age, 37 days; 55.7%boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections—including 32 with bacteremia and 15 with urinary tract infections—and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87%(95%CI, 73%-95%) sensitivity and 89% (95%CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94%(95%CI, 70%-100%) sensitivity and 95%(95%CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95%CI, 0.30–0.43). CONCLUSIONS AND RELEVANCE In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with vs without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice. PMID:27552618

Prevalence of HHV-6 in cerebrospinal fluid of children younger than 2 years of age with febrile convulsion.

PubMed

Mamishi, Setareh; Kamrani, Laura; Mohammadpour, Masoud; Yavarian, Jila

2014-04-01

Febrile convulsion is a common disorder in children. Viral infections such as human herpes virus 6 (HHV-6) which results in roseola infantum may contribute to developing seizure. The objective of this study was to determine the prevalence of HHV-6 by detecting DNA in cerebrospinal fluid (CSF) of children with febrile convulsion and without any rash of roseola infantum. In this descriptive cross-sectional study, CSF of 100 children younger than 2 years of age with febrile convulsion was evaluated for detecting HHV-6 DNA by PCR. All of them were referred to emergency ward in Pediatric Medical Center from March 2010 to March 2011. General information, clinical manifestations, laboratory tests and outcomes were collected in the questionnaires. One hundred children including 59 males and 41 females were evaluated. HHV-6 was detected from CSF in six patients (6%) by PCR. Mean age was 8 months old. All children were younger than 12 months old. The most common primary manifestation was fever alone. None of them had rash. Majority of cases occurred in winter. All patients recovered without any encephalitis. These findings showed that primary infection with HHV-6 is frequently associated with febrile convulsion in infants which may be at risk for subsequent development of epilepsy.

Urinary Biomarkers for Screening for Renal Scarring in Children with Febrile Urinary Tract Infection: Pilot Study.

PubMed

Kitao, Tetsuya; Kimata, Takahisa; Yamanouchi, Sohsaku; Kato, Shogo; Tsuji, Shoji; Kaneko, Kazunari

2015-09-01

Recurrent febrile urinary tract infections during infancy cause renal scarring, which is characterized by progressive focal interstitial fibrosis and may lead to renal failure. Renal scarring can be diagnosed through scintigraphy, although it seems impractical to perform renal scintigraphy for all infants with febrile urinary tract infections. Therefore, it is important to search for a biomarker to identify the presence of renal scarring. We hypothesized that urinary biomarkers of nephropathy may increase in infants with renal scarring following febrile urinary tract infections. A total of 49 infants who underwent renal scintigraphy for febrile urinary tract infections were enrolled in the study. Several measurements were performed using urine samples, including total proteins, beta2-microglobulins, N-acetyl-β-D-glucosaminidase, neutrophil gelatinase associated lipocalin, liver-type fatty acid binding protein and angiotensinogen. Values were corrected by creatinine and compared between patients with and without renal scarring. Among urinary biomarkers only angiotensinogen in patients with scarring (median 14.6 μg/gm creatinine) demonstrated significantly higher levels than in patients without scarring (3.6 μg/gm creatinine, p <0.001). Urinary angiotensinogen may be useful for diagnosing the presence of renal scarring. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Delayed treatment of the first febrile urinary tract infection in early childhood increased the risk of renal scarring.

PubMed

Karavanaki, Kyriaki A; Soldatou, Alexandra; Koufadaki, Athina Maria; Tsentidis, Charalampos; Haliotis, Fotis A; Stefanidis, Constantinos J

2017-01-01

This study evaluated the controversial relationship between the duration of fever before treatment initiation (FBT) for a febrile urinary tract infection (UTI), with renal scarring based on dimercaptosuccinic acid scintigraphy (DMSA) findings. The inpatient records of 148 children under two years of age with a first episode of febrile UTI were analysed. Acute and repeat DMSA findings, and clinical and laboratory parameters were evaluated. Acute DMSA showed that 76 of the 148 children with a febrile UTI had renal lesions: 20 were mild, and 56 were moderate or severe. Repeat DMSA showed renal scarring in 34 patients. The only factors associated with the development of renal scars in the repeat DMSA were FBT of more than 72 hours, the presence and severity of vesicoureteral reflux and increased procalcitonin levels and absolute neutrophil counts. Multiple regression analysis showed that an FBT above 72 hours was the only significant factor that predicted renal scars. Delay in treatment initiation of 72 hours or more was a risk factor for permanent renal scars after the first episode of febrile UTI. Other associated factors were increased procalcitonin and absolute neutrophil count on admission and the presence and severity of vesicouretal reflux. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Risk factors for urinary tract infection in children with urinary urgency.

PubMed

Gondim, Rhaiana; Azevedo, Roberta; Braga, Ana Aparecida Nascimento Martinelli; Veiga, Maria Luiza; Barroso, Ubirajara

2018-01-01

To identify which independent variable would be strong predictor of febrile urinary tract infection (UTI) in children and adolescents with overactive bladder. A search was made of the institute's database for all patients diagnosed with overactive bladder over the preceding four years. Children and adolescents under 18 years of age with overactive bladder and no neurological or anatomical alterations of the lower urinary tract were included in the study. The independent variables were: sex, age, ethnicity (Brazilians of African descendence/others), the presence of urinary urgency, daytime incontinence, enuresis, frequent urination, infrequent voiding (≤3 voids/day), nocturia, holding maneuvers, straining to void, intermittent urinary flow, constipation and encopresis. An analysis was conducted to identify patients with febrile UTI and subsequently determine predictors of this condition. Univariate and multivariate analyses were performed. Overall, 326 patients (214 girls/112 boys) were evaluated. The mean age of the patients was 7.7±3.19 years (± standard deviation). The incidence of febrile UTI was 39.2%. Being female and infrequent voiding were factors significantly associated with febrile UTI, both in the univariate and multivariate analyses. These results show that being female and infrequent voiding constituted significant risk factors for a diagnosis of febrile UTI in these children. Copyright® by the International Brazilian Journal of Urology.

Serologic surveillance for West Nile virus and other flaviviruses in febrile patients, encephalitic patients, and asymptomatic blood donors in northern Mexico.

PubMed

Rodríguez, María de Lourdes Garza; Rodriguez, Diana R Rodríguez; Blitvich, Bradley J; López, Miguel A Reyes; Fernández-Salas, Ildefonso; Jimenez, Javier Ramos; Farfán-Ale, José A; Tamez, Rogelio Cazares; Longoria, César Martinez; Aguilar, Maria I Tavitas; Rivas-Estilla, Ana Maria

2010-03-01

A clinical and serological investigation was performed to determine the presence of West Nile virus (WNV) among febrile and encephalitic patients in northern Mexico. In addition, asymptomatic blood donors were serologically assayed for WNV to determine the seroprevalence of WNV in the general population. The study cohort consisted of 1432 individuals (588 febrile patients, 44 encephalitic patients, and 800 asymptomatic blood donors). All subjects were negative for WNV IgM. Sixty subjects were reactive for dengue virus (DENV) IgM (16 blood donors and 44 febrile patients). A subset (n = 425) of individuals was also screened by ELISA for flavivirus IgG. The prevalence of flavivirus IgG in febrile patients, encephalitic patients, and blood donors ranged from 40% to 59%. A subset (n = 147) of sera reactive for flavivirus IgG was further tested by plaque reduction neutralization test. Six individuals with no history of travel during the preceding 12 months were seropositive for WNV. Another 65 individuals were seropositive for DENV1 and 24 were seropositive for DENV2. The high prevalence of dengue antibodies in northern Mexico appears to limit the incidence of WNV infection in this region. Article Summary Line: Antibodies to WNV, DENV-1, and DENV-2 were identified in humans in northern Mexico.

Fever without localizing signs in children: a review in the post-Hib and postpneumococcal era.

PubMed

Chancey, R J; Jhaveri, R

2009-10-01

Fever without localizing signs in young infants and children has been a common problem for pediatric practitioners for decades. Prior to the introduction of vaccines against common childhood invasive pathogens, including Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae, extensive diagnostic workup of febrile infants and children was warranted to avoid missing serious bacterial infections. At that time, occult bacteremia occurred at a rate of 5.7%. Evaluation of febrile children was based on high and low risk criteria established by Dagan et al. and applied further in suggested clinical practice guidelines in 1993. After the introduction of effective Hib and PCV7 vaccines, the rate of serious bacterial infections has dramatically fallen, with occult bacteremia rates now 0-0.74%. Changes in the administration of intrapartum antibiotics to women at risk for transmitting Group B Streptococcus to neonates has significantly reduced the rates of early onset GBS disease in infants. Although the risk of serious infections is extremely low, management and evaluation of febrile children has remained essentially unchanged. This review summarizes the historical context of the management of the febrile child, discusses the developments that have been cause for re-evaluation and provides recommendations for management of the febrile child in this current era.

Frequency and Clinical Features of Dengue Infection in a Schoolchildren Cohort from Medellin, Colombia

PubMed Central

Restrepo, Berta Nelly; Piedrahita, Leidy Diana; Agudelo, Ivony Yireth; Parra-Henao, Gabriel; Osorio, Jorge E.

2012-01-01

To determine the incidence of dengue infection, we established active surveillance of febrile episodes in a cohort of schoolchildren from three schools in Medellin, Colombia. We followed a cohort of 2,379 schoolchildren in 2010 and followed 1,840 of these children the following year. During the follow-up time, 264 schoolchildren displayed 297 febrile episodes; of these, 23 episodes (7.7%) were caused by acute dengue infection. All four dengue serotypes were found, and all of the cases were mild. The most common symptoms in the dengue cases compared with those in other febrile illness were asthenia (96% versus 87%), anorexia (78% versus 57%), rhinorrhea (65.2% versus 58%), abdominal pain (56.5% versus 47.8%), arthralgia (43% versus 33%), and positive tourniquet test (13% versus 3%). This difference was not statistically significant. Pulse was elevated, and systolic arterial pressure was lower in dengue cases compared with other febrile illness (P < 0.05). Mosquito indexes were determined in 8 children's houses and in the schools. Aedes aegypti adults were found in both households and in schools, whereas Aedes aegypti larvae were found only in schools. These results showed an elevated dengue frequency in children, with symptoms similar to those of other febrile illness and transmission risk in households and schools. PMID:23304167

Febrile neutropaenia and chemotherapy discontinuation in women aged 70 years or older receiving adjuvant chemotherapy for early breast cancer.

PubMed

Adjogatse, D; Thanopoulou, E; Okines, A; Thillai, K; Tasker, F; Johnston, S R D; Harper-Wynne, C; Torrisi, E; Ring, A

2014-11-01

Low rates of adjuvant chemotherapy use are frequently reported in older women with early breast cancer. One of the reasons for this may be the risk of febrile neutropaenia or the perception that older patients will probably not complete the chemotherapy course prescribed. There are no data regarding these adverse outcomes in routine clinical practice. We identified 128 patients aged 70 years or over who received neoadjuvant or adjuvant chemotherapy for early breast cancer in seven UK cancer centres between 2006 and 2012. Data were collected regarding standard clinical and pathological variables and treatment toxicity and outcomes. Twenty-four patients (19%) had an episode of febrile neutropaenia. Overall, 27 patients (21%) did not complete their planned therapy. Chemotherapy discontinuation was more common in those patients with an episode of febrile neutropaenia (46% versus 16%, P = 0.004). Thirty patients (23%) were admitted with chemotherapy-related complications. There were no treatment-related deaths. The rates of febrile neutropaenia and treatment discontinuation are high in women aged 70 years or over receiving adjuvant chemotherapy for breast cancer. Close attention should be paid to the choice or regimen and the use of supportive therapies in this patient population. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Temperature management in haematology patients with febrile neutropenia: a practice survey.

PubMed

Weinkove, Robert; Clay, Jennifer; Wood, Catherine

2013-04-19

To assess the attitudes of clinicians to temperature management in haematology patients with febrile neutropenia. An online scenario-based survey was circulated to consultant members of the New Zealand branch of the Haematology Society of Australia and New Zealand, to haematology advanced trainees, and to nursing representatives at each haematology department in New Zealand. Eighty-eight responses were obtained, from 34 doctors and 54 nurses. Most respondents would advise a neutropenic patient to take paracetamol as needed for pain. Median temperature intervention threshold for an asymptomatic patient with febrile neutropenia was higher for doctors than for nurses (38.5 versus 38.0 degrees Celcius), despite considerable heterogeneity. Both groups indicated they would intervene at a median 38.0 degrees Celcius for a patient with rigors. Paracetamol was the preferred first-line cooling measure, with physical methods second-line, and pethidine third-line. All respondents favoured oral over intravenous or rectal paracetamol. Most believed a clinical trial of antipyretic treatment for febrile neutropenia was warranted, and indicated willingness to enrol their patients in such a study. This survey documents clinicians' preferred temperature intervention thresholds and methods for haematology patients with neutropenic fever, and shows considerable variation in practice. Most respondents supported a trial of antipyretic management in febrile neutropenia.

Epigenetic activation of SIN1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial–mesenchymal transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Zhongwu; Wang, Yaqin; Wang, Yuemei

Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is an essential component of mTORC2. Previous studies have shown that SIN1 is a key regulator of Akt pathway which plays an important role in various pathological conditions including cancer. While its effects and mechanisms on the progression of NSCLC remain unknown. In this study, we report that SIN1 is able to promote the growth and migration of NSCLC cells both in vitro and in vivo. Overexpression of SIN1 promoted A549 and H1299 cells proliferation by both MTT and colony formation assays. Consistently, knockdown of SIN1 inhibited the proliferation of these cells. In transwell assay,more » overexpression of SIN1 increased the migration of A549 and H1299 cells, while SIN1 knockdown reduced their migration. In a tumor xenograft model, overexpression of SIN1 promoted tumor growth of A549 cells in vivo, while SIN1 knockdown suppresses the tumor growth. We also found a mechanistic link between SIN1 and H3K4me3, H3K4me3 is involved in SIN1 upregulation. Moreover, SIN1 can significantly promote the in vitro migration and invasion of NSCLC cells via induction epithelial mesenchymal transition (EMT) process, which subsequently leads to transcriptional downregulation of epithelial marker E-cadherin and upregulation of mesenchymal markers N-cadherin and Vimentin expression. Together, our results reveal that SIN1 plays an important role in NSCLC and SIN1 is a potential biomarker and a promising target in the treatment of NSCLC.« less

Extended versus Bolus Infusion of Broad Spectrum β-Lactams for Febrile Neutropenia: an Unblinded Randomized Trial.

PubMed

Ram, Ron; Halavy, Yael; Amit, Odelia; Paran, Yael; Katchman, Eugene; Yachini, Bruria; Kor, Svetlana; Avivi, Irit; Ben-Ami, Ronen

2018-03-28

Febrile neutropenia may be a sign of severe infection, and is associated with significant morbidity and mortality in high-risk patients with hematologic malignancies. Extended infusion of β-lactam antibiotics is associated with greater clinical response than is bolus infusion in non-neutropenic critically ill patients, but data are lacking for febrile neutropenic patients. We designed a single-center, non-blinded randomized trial comparing extended infusion (4 hours) and bolus infusion (30 minutes) of piperacillin-tazobactam or ceftazidime in high-risk patients with febrile neutropenia. The primary end-point was overall response on day 4, defined as the combination of resolution of fever, sterile blood cultures, resolution of clinical signs and symptoms, and no need for a change in the antibiotic regimen. Outcome was adjudicated by investigators blinded to treatment allocation. Of 123 enrolled patients, 105 had febrile neutropenia and were included in the intention-to-treat analysis: 47 in the extended infusion arm and 58 in the bolus infusion arm. Overall response occurred in 35 (74.4%) patients treated with extended infusion and 32 (55.1%) patients treated with bolus infusion (P=0.044). The superiority of extended infusion compared with bolus infusion was greatest for patients with clinically documented infections (overall response, 68.4% [13/19] versus 35.7% [10/28]; P=0.039), and specifically for those with pneumonia (80% [4/5] versus 0% [0/8]; P=0.007). Extended infusion of β-lactams is associated with superior treatment outcomes as compared with bolus infusion for high-risk patients with febrile neutropenia. The benefit of extended β-lactam infusion may be greatest for patients with pulmonary infections.

Managing the Sick Child in the Era of Declining Malaria Transmission: Development of ALMANACH, an Electronic Algorithm for Appropriate Use of Antimicrobials.

PubMed

Rambaud-Althaus, Clotilde; Shao, Amani Flexson; Kahama-Maro, Judith; Genton, Blaise; d'Acremont, Valérie

2015-01-01

To review the available knowledge on epidemiology and diagnoses of acute infections in children aged 2 to 59 months in primary care setting and develop an electronic algorithm for the Integrated Management of Childhood Illness to reach optimal clinical outcome and rational use of medicines. A structured literature review in Medline, Embase and the Cochrane Database of Systematic Review (CDRS) looked for available estimations of diseases prevalence in outpatients aged 2-59 months, and for available evidence on i) accuracy of clinical predictors, and ii) performance of point-of-care tests for targeted diseases. A new algorithm for the management of childhood illness (ALMANACH) was designed based on evidence retrieved and results of a study on etiologies of fever in Tanzanian children outpatients. The major changes in ALMANACH compared to IMCI (2008 version) are the following: i) assessment of 10 danger signs, ii) classification of non-severe children into febrile and non-febrile illness, the latter receiving no antibiotics, iii) classification of pneumonia based on a respiratory rate threshold of 50 assessed twice for febrile children 12-59 months; iv) malaria rapid diagnostic test performed for all febrile children. In the absence of identified source of fever at the end of the assessment, v) urine dipstick performed for febrile children <2 years to consider urinary tract infection, vi) classification of 'possible typhoid' for febrile children >2 years with abdominal tenderness; and lastly vii) classification of 'likely viral infection' in case of negative results. This smartphone-run algorithm based on new evidence and two point-of-care tests should improve the quality of care of <5 year children and lead to more rational use of antimicrobials.

Female Sex Hormones Influence the Febrile Response Induced by Lipopolysaccharide, Cytokines and Prostaglandins but not by Interleukin-1β in Rats.

PubMed

Brito, H O; Radulski, D R; Wilhelms, D B; Stojakovic, A; Brito, L M O; Engblom, D; Franco, C R C; Zampronio, A R

2016-10-01

There are differences in the immune response, and particularly fever, between males and females. In the present study, we investigated how the febrile responses induced by lipopolysaccharide (LPS) and different endogenous pyrogens were affected by female gonadal hormones. The febrile response to i.p. injection of LPS (50 μg/kg) was 40% lower in female rats compared to male or ovariectomised (OVX) female rats. Accordingly, oestrogen replacement in OVX animals reduced LPS-induced fever. Treatment with the prostaglandin synthesis inhibitor indomethacin (2 mg/kg, i.p. 30 min before) reduced the febrile response induced by LPS in both OVX (88%) and sham-operated (71%) rats. In line with the enhanced fever in OVX rats, there was increased expression of cyclooxygenase-2 (COX-2) in the hypothalamus and elevated levels of prostaglandin E 2 (PGE 2 ). In addition, OVX rats were hyper-responsive to PGE 2 injected i.c.v. By contrast to the enhanced fever in response to LPS and PGE 2 , the febrile response induced by i.c.v. injection of interleukin (IL)-1β was unaffected by ovariectomy, whereas the responses induced by tumour necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-1α were completely abrogated. These results suggest that the mediators involved in the febrile response in females are similar to males, although the reduction of female hormones may decrease the responsiveness of some mediators such as TNF-α and MIP-1α. Compensatory mechanisms may be activated in females after ovariectomy such as an augmented synthesis of COX-2 and PGE 2 . © 2016 British Society for Neuroendocrinology.

Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures.

PubMed

Awad, Patricia N; Sanon, Nathalie T; Chattopadhyaya, Bidisha; Carriço, Josianne Nunes; Ouardouz, Mohamed; Gagné, Jonathan; Duss, Sandra; Wolf, Daniele; Desgent, Sébastien; Cancedda, Laura; Carmant, Lionel; Di Cristo, Graziella

2016-07-01

Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

Sickness behavior in feverish children is independent of the severity of fever. An observational, multicenter study.

PubMed

Corrard, François; Copin, Christian; Wollner, Alain; Elbez, Annie; Derkx, Véronique; Bechet, Stéphane; Levy, Corinne; Boucherat, Michel; Cohen, Robert

2017-01-01

Behavioral changes in a febrile child are usually considered to stem from the fever. We studied sickness behavior (SB) in terms of its clinical components and its relation to fever. This observational, multicenter study included children aged 6 months to 3 years who were either febrile (fever ≥12 hours, ≥ 39°C and ≥38°C at inclusion) or non-febrile and well. The child had to have been awake for the 2 hours preceding the consultation and cared for by the parent who brought him/her to the doctor. SB was evaluated according to 6 parameters over this 2-hour period: time spent playing, distance covered, time spent seeking comfort, time spent whining or crying, time spent in a state of irritation or of anger, most distorted facial expression. Two parameters were assessed for the 24-hour period preceding the consultation: time spent sleeping and appetite. The parent reported the degree of change in these parameters compared with the usual situation, using rating scales. 200 febrile children (most with nonspecific upper respiratory infections) and 200 non-febrile children were included. The mean values of the 8 parameters differed significantly (p<0.001) between the 2 groups and were independent of the height of fever at inclusion in the febrile children. In the study conditions, paracetamol failed to improve SB when the child was still feverish. The 8 parameters suggested that SB and fever are two independent manifestations that are activated simultaneously during an infection. This independence is in harmony with recommendations to treat the discomfort of SB and not the fever.

Fever in trauma patients: evaluation of risk factors, including traumatic brain injury.

PubMed

Bengualid, Victoria; Talari, Goutham; Rubin, David; Albaeni, Aiham; Ciubotaru, Ronald L; Berger, Judith

2015-03-01

The role of fever in trauma patients remains unclear. Fever occurs as a response to release of cytokines and prostaglandins by white blood cells. Many factors, including trauma, can trigger release of these factors. To determine whether (1) fever in the first 48 hours is related to a favorable outcome in trauma patients and (2) fever is more common in patients with head trauma. Retrospective study of trauma patients admitted to the intensive care unit for at least 2 days. Data were analyzed by using multivariate analysis. Of 162 patients studied, 40% had fever during the first 48 hours. Febrile patients had higher mortality rates than did afebrile patients. When adjusted for severity of injuries, fever did not correlate with mortality. Neither the incidence of fever in the first 48 hours after admission to the intensive care unit nor the number of days febrile in the unit differed between patients with and patients without head trauma (traumatic brain injury). About 70% of febrile patients did not have a source found for their fever. Febrile patients without an identified source of infection had lower peak white blood cell counts, lower maximum body temperature, and higher minimum platelet counts than did febrile patients who had an infectious source identified. The most common infection was pneumonia. No relationship was found between the presence of fever during the first 48 hours and mortality. Patients with traumatic brain injury did not have a higher incidence of fever than did patients without traumatic brain injury. About 30% of febrile patients had an identifiable source of infection. Further studies are needed to understand the origin and role of fever in trauma patients. ©2015 American Association of Critical-Care Nurses.

Managing the Sick Child in the Era of Declining Malaria Transmission: Development of ALMANACH, an Electronic Algorithm for Appropriate Use of Antimicrobials

PubMed Central

Rambaud-Althaus, Clotilde; Shao, Amani Flexson; Genton, Blaise; d’Acremont, Valérie

2015-01-01

Objective To review the available knowledge on epidemiology and diagnoses of acute infections in children aged 2 to 59 months in primary care setting and develop an electronic algorithm for the Integrated Management of Childhood Illness to reach optimal clinical outcome and rational use of medicines. Methods A structured literature review in Medline, Embase and the Cochrane Database of Systematic Review (CDRS) looked for available estimations of diseases prevalence in outpatients aged 2-59 months, and for available evidence on i) accuracy of clinical predictors, and ii) performance of point-of-care tests for targeted diseases. A new algorithm for the management of childhood illness (ALMANACH) was designed based on evidence retrieved and results of a study on etiologies of fever in Tanzanian children outpatients. Findings The major changes in ALMANACH compared to IMCI (2008 version) are the following: i) assessment of 10 danger signs, ii) classification of non-severe children into febrile and non-febrile illness, the latter receiving no antibiotics, iii) classification of pneumonia based on a respiratory rate threshold of 50 assessed twice for febrile children 12-59 months; iv) malaria rapid diagnostic test performed for all febrile children. In the absence of identified source of fever at the end of the assessment, v) urine dipstick performed for febrile children <2years to consider urinary tract infection, vi) classification of ‘possible typhoid’ for febrile children >2 years with abdominal tenderness; and lastly vii) classification of ‘likely viral infection’ in case of negative results. Conclusion This smartphone-run algorithm based on new evidence and two point-of-care tests should improve the quality of care of <5 year children and lead to more rational use of antimicrobials. PMID:26161753

Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy

PubMed Central

Kasai, Mari; Fukuda, Takeshi; Ichimura, Tomoyuki; Yasui, Tomoyo; Sumi, Toshiyuki

2015-01-01

Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24–84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1–12 days) and 3.4 days (range 1–9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (P<0.0001), less than five previous chemotherapy cycles (P=0.02), disseminated disease (P=0.03), platinum-based regimens (P<0.0001), taxane-containing regimens (P<0.0001), and combined therapy (P<0.0001). Febrile neutropenia was associated with poor performance status (P<0.0001), no previous chemotherapy (P<0.05), disseminated disease (P<0.0001), and distant metastatic disease (P=0.03). Neither chemotherapy-induced neutropenia nor febrile neutropenia was associated with bone marrow metastases or previous radiotherapy. By identifying risk factors for febrile neutropenia, such as performance status, no previous chemotherapy, disseminated disease, and distant metastatic disease, the safe management of chemotherapy-induced neutropenia may be possible in patients with gynecologic malignancy. PMID:26267078

Causative Pathogens of Febrile Neutropaenia in Children Treated for Acute Lymphoblastic Leukaemia.

PubMed

Lam, Joyce Cm; Chai, Jie Yang; Wong, Yi Ling; Tan, Natalie Wh; Ha, Christina Tt; Chan, Mei Yoke; Tan, Ah Moy

2015-11-01

Treatment of acute lymphoblastic leukaemia (ALL) using intensive chemotherapy has resulted in high cure rates but also substantial morbidity. Infective complications represent a significant proportion of treatment-related toxicity. The objective of this study was to describe the microbiological aetiology and clinical outcome of episodes of chemotherapy-induced febrile neutropaenia in a cohort of children treated for ALL at our institution. Patients with ALL were treated with either the HKSGALL93 or the Malaysia-Singapore (Ma-Spore) 2003 chemotherapy protocols. The records of 197 patients who completed the intensive phase of treatment, defined as the period of treatment from induction, central nervous system (CNS)-directed therapy to reinduction from June 2000 to January 2010 were retrospectively reviewed. There were a total of 587 episodes of febrile neutropaenia in 197 patients, translating to an overall rate of 2.98 episodes per patient. A causative pathogen was isolated in 22.7% of episodes. An equal proportion of Gram-positive bacteria (36.4%) and Gram-negative bacteria (36.4%) were most frequently isolated followed by viral pathogens (17.4%), fungal pathogens (8.4%) and other bacteria (1.2%). Fungal organisms accounted for a higher proportion of clinically severe episodes of febrile neutropaenia requiring admission to the high-dependency or intensive care unit (23.1%). The overall mortality rate from all episodes was 1.5%. Febrile neutropaenia continues to be of concern in ALL patients undergoing intensive chemotherapy. The majority of episodes will not have an identifiable causative organism. Gram-positive bacteria and Gram-negative bacteria were the most common causative pathogens identified. With appropriate antimicrobial therapy and supportive management, the overall risk of mortality from febrile neutropaenia is extremely low.

Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy.

PubMed

Hashiguchi, Yasunori; Kasai, Mari; Fukuda, Takeshi; Ichimura, Tomoyuki; Yasui, Tomoyo; Sumi, Toshiyuki

2015-11-01

Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24-84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1-12 days) and 3.4 days (range 1-9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (P<0.0001), less than five previous chemotherapy cycles (P=0.02), disseminated disease (P=0.03), platinum-based regimens (P<0.0001), taxane-containing regimens (P<0.0001), and combined therapy (P<0.0001). Febrile neutropenia was associated with poor performance status (P<0.0001), no previous chemotherapy (P<0.05), disseminated disease (P<0.0001), and distant metastatic disease (P=0.03). Neither chemotherapy-induced neutropenia nor febrile neutropenia was associated with bone marrow metastases or previous radiotherapy. By identifying risk factors for febrile neutropenia, such as performance status, no previous chemotherapy, disseminated disease, and distant metastatic disease, the safe management of chemotherapy-induced neutropenia may be possible in patients with gynecologic malignancy.

Implementation of an evidence-based order set to impact initial antibiotic time intervals in adult febrile neutropenia.

PubMed

Best, Janie T; Frith, Karen; Anderson, Faye; Rapp, Carla Gene; Rioux, Lisa; Ciccarello, Christina

2011-11-01

To evaluate the impact of the implementation of a standardized order set on the time interval in initiation of antibiotic therapy for adult patients with cancer and febrile neutropenia. Practice change. The oncology unit of an urban hospital in the south-eastern United States. Adult patients with cancer and febrile neutropenia admitted six months prior to (n = 30) or during the three months following (n = 23) implementation of the order set. Literature regarding febrile neutropenia, use of order sets, and change process was reviewed. In addition, a retrospective and concurrent chart review was conducted for adult patients admitted with febrile neutropenia. Time intervals were analyzed using SPSS® software, version 18. Initial antibiotic times, order-set use, and length of stay. An overall reduction in time intervals for initiation of antibiotic therapy was observed for presentation (t = 2.25; degrees of freedom [df] = 37; p = 0.031) and order (t = 2.67; df = 40.17; p = 0.012) to antibiotic administration, with an order-set usage of 31% in the inpatient unit and 71% in the emergency department. Findings in the presence of low order-set usage suggest that staff education and placement of the order-set antibiotics in unit-based medication dispensing machines helped reduce time intervals for initial antibiotic therapy. The use of an evidence-based approach to nursing care is essential to achieving the best outcomes for patients with febrile neutropenia. Incorporation of current evidence into an order set to guide clinical practice and comprehensive nurse, pharmacy, and physician education are needed for the successful implementation of evidence-based practice changes.

[Febrile neutropenia at the emergency department of a cancer hospital].

PubMed

Debey, C; Meert, A-P; Berghmans, T; Thomas, J M; Sculier, J P

2011-01-01

Febrile neutropenia is an important cause of fever in the cancer patient. When he/she is undergoing chemotherapy, the priority is to exclude that complication because it requires rapid administration of empiric broad-spectrum antibiotics. We have studied the rate and characteristics of febrile neutropenia in cancer patients consulting in a emergency department. We have conducted a retrospective study in the emergency department of a cancer hospital over the year 2008. Every patient with cancer and fever > or = 38 degrees C was included. Over 2.130 consultations, 408 were selected (313 patients) including 21.6% (88) for febrile neutropenia. A focal symptom or physical sign was present in the majority of the cases. 88% were assessed as low risk for severe complications and about half of them received oral antibiotics. There were only a few patients with a nude fever for which it was difficult to make a hypothetical diagnosis in order to administer a probabilistic treatment. The majority of the consultations lead to hospital admission. Over the 80 hospitalisations, 6 deaths occurred. There was no death among the patients who remained ambulatory. In conclusion, our study shows that febrile neutropenia is frequent in ambulatory cancer patients presenting with fever and that in the majority of the cases, it is associated with a low risk. In such a situation, ambulatory management is more and more often considered or, at least, a rapid discharge after a short admission in case of low risk febrile neutropenia. In that context, the role of the general practioner has to be emphasised and to facilitate the outpatient management, we propose an algorithm that requires validation.

Identification of sinensetin metabolites in rat urine by an isotope-labeling method and ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Wei, Guor-Jien; Sheen, Jenn-Feng; Lu, Wen-Chien; Hwang, Lucy Sun; Ho, Chi-Tang; Lin, Ching-I

2013-05-29

Sinensetin (SIN), one of the major polymethoxyflavones (PMFs) contained mainly in the citrus peels, has been reported to possess various bioactivities, including antifungal, antimutagenic, anticancer, and anti-inflammatory activities. Although the biotransformation of SIN in fungi and insects has been reported, the information about the metabolism of SIN in mammals is still unclear. In this study, formation of SIN metabolites in rats was investigated. Four isotope-labeled SINs ([4'-D3]SIN, [3'-D3]SIN, [5-D3]SIN, and [6-D3]SIN) were synthesized and administered to rat. The urine samples were collected and main metabolites were monitored by ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry. The administered compound and four SIN metabolites were detected in rat urine. These metabolites were identified as 4'-hydroxy-5,6,7,3'-tetramethoxyflavone, 5-hydroxy-6,7,3',4'-tetramethoxyflavone, 6-hydroxy-5,7,3',4'-tetramethoxyflavone, and 7-hydroxy-5,6,3',4'-tetramethoxyflavone sulfate.

Managing fever and febrile symptoms in HIV: evidence-based approaches.

PubMed

Holtzclaw, Barbara J

2013-01-01

Fever remains a common symptom for persons living with HIV (PLWH) despite improving overall health and survival rates. Elevated body temperatures are among the classic symptoms of primary HIV infection and are later harbingers of opportunistic infections. Therapeutic agents, including antiretrovirals, antifungals, interleukins, interferon, and blood products, can produce fever. While research shows that fever holds immunological benefits, and outdated practices to cool febrile patients create distress and energy expenditure from shivering, "fever phobia" persists. This article discusses the evolution of understanding about fever and HIV infection, its influence on caregivers and PLWH, and the existing evidence surrounding (a) physiological threats and benefits of the febrile response for PLWH, (b) goals underpinning assessment and management of fever and related febrile symptoms, and (c) development and testing of fever-management interventions. This evidence is summarized with rationale for the need to educate both public and professionals about the complexities of fever. Copyright © 2013 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis

PubMed Central

Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

2006-01-01

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2–0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the Ih current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes. PMID:16819552

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

PubMed

Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

2006-07-01

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced febrile neutropenia in patients with hematological malignancies.

PubMed

Shinohara, Akihito; Yoshiki, Yumiko; Masamoto, Yosuke; Hangaishi, Akira; Nannya, Yasuhito; Kurokawa, Mineo

2013-04-01

Recent studies have shown the prophylactic efficacy of fluoroquinolones against infections in patients with chemotherapy-induced neutropenia. However, little is known about the differences between fluoroquinolones, and there are some concerns about the emergence of resistant bacteria. In this retrospective study, we compared the prophylactic efficacy of moxifloxacin (MFLX) and tosufloxacin (TFLX) for chemotherapy-induced febrile neutropenia. The cumulative incidences of febrile neutropenia were 74.7% (59 of 79) in the MFLX group and 81.1% (219 of 270) in the TFLX group (log-rank test p = 0.044). Subgroup analysis revealed a more prominent prophylactic advantage of MFLX in patients with acute myeloid leukemia (AML) or long duration of neutropenia (p = 0.013 and 0.008, respectively). There were no significant differences in the incidences of adverse events and fluoroquinolone resistant bacteria in both groups. This study indicates that prophylaxis with MFLX is more beneficial to reduce febrile neutropenia episodes than TFLX, especially in patients with high-risk disease.

Observation of patients with vesicoureteral reflux off antibiotic prophylaxis: physician bias on patient selection and risk factors for recurrent febrile urinary tract infection.

PubMed

Drzewiecki, Beth A; Thomas, John C; Pope, John C; Adams, Mark C; Brock, John W; Tanaka, Stacy T

2012-10-01

Observation off continuous antibiotic prophylaxis is an option for vesicoureteral reflux. We evaluated the characteristics of patients observed off continuous antibiotic prophylaxis and risk factors for febrile urinary tract infection. We identified children 1 to 18 years old with primary vesicoureteral reflux between January 1, 2010 and December 31, 2010. We excluded patients with prior surgical correction from analysis. We recorded age, gender, race/ethnicity, primary language, insurance carrier, age at vesicoureteral reflux diagnosis, initial presentation and vesicoureteral reflux severity. We quantified bladder and bowel dysfunction with a validated questionnaire if toilet trained. We compared patients off vs on continuous antibiotic prophylaxis with the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. We used a univariate Cox proportional hazards model to assess predictors of febrile urinary tract infection during observation off continuous antibiotic prophylaxis. Of 529 eligible patients 224 were observed off continuous antibiotic prophylaxis. Patients off continuous antibiotic prophylaxis tended to be older (p <0.001), to be older at diagnosis (p <0.001), to have an initial presentation other than febrile urinary tract infection (p = 0.05), to have nondilating vesicoureteral reflux on most recent cystogram (p <0.001) and to have lower bladder/bowel dysfunction scores if toilet trained (p <0.001). Of the patients off continuous antibiotic prophylaxis a febrile urinary tract infection developed in 19 (8.5%). Risk factors associated with febrile urinary tract infection included initial presentation of multiple febrile urinary tract infections (p = 0.03), older age at diagnosis (p = 0.03) and older age starting observation off continuous antibiotic prophylaxis (p = 0.0003). Criteria to select patients with vesicoureteral reflux for observation off continuous antibiotic prophylaxis remain poorly defined in the literature. Observation will fail in a subset of patients with vesicoureteral reflux. Physician biases regarding patient selection for observation off continuous antibiotic prophylaxis should be considered when interpreting studies that evaluate treatment strategies. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Evaluation of febrile children with petechial rashes: is there consensus among pediatricians?

PubMed

Nelson, D G; Leake, J; Bradley, J; Kuppermann, N

1998-12-01

The evaluation of febrile children with petechial rashes evokes controversy. Although many of these children have viral infections, on occasion such patients may be infected with Neisseria meningitidis. To investigate differences in practice trends for the evaluation and management of non-toxic-appearing febrile children with petechial rashes among pediatric specialty groups. We surveyed 833 pediatricians in 4 specialties [community (CGP) and academic (AGP) general pediatrics, emergency medicine (EM) and infectious diseases] regarding 4 hypothetical non-toxic-appearing febrile children ages 1, 2, 5 and 7 years. The patients differed with regard to clinical appearance, distribution of petechiae and complete blood count results. We compared specialty group responses, adjusting for practice setting, population size and years in practice using multiple logistic regression analysis. The survey was completed and returned by 416 (50%) pediatricians. There was substantial variation in the evaluation of the 2 younger febrile children without clear sources for their petechiae. For the 1-year-old the overall blood culture (BCx) rate was 82%, with the EM group (91%) more often requesting BCx than either the CGP (76%) or AGP (73%, P=0.001) groups. The overall hospital admission rate was 31%, with CGP less often requesting admission than infectious disease pediatricians (22% vs. 40%, P=0.007). In the regression analysis the only significant difference between groups was in BCx rate between the EM and AGP groups. For the 2-year-old the overall rate of BCx was 95%, lumbar puncture was 41% and admission was 44%, with no significant differences among groups. For the scenarios involving the 2 older febrile children with sources for their petechiae, the majority of respondents chose neither lumbar puncture nor admission. There was disagreement regarding BCx, both within and between groups, although most of the between group differences did not persist in the regression analysis. There are substantial differences among pediatricians in the evaluation of young non-toxic-appearing febrile children with petechial rashes. Although there are some differences between pediatric subspecialties, most of these differences do not persist after adjusting for practice setting, population size and physician experience.

Venezuelan equine encephalitis and Oropouche virus infections among Peruvian army troops in the Amazon region of Peru.

PubMed

Watts, D M; Lavera, V; Callahan, J; Rossi, C; Oberste, M S; Roehrig, J T; Cropp, C B; Karabatsos, N; Smith, J F; Gubler, D J; Wooster, M T; Nelson, W M; Hayes, C G

1997-06-01

An outbreak of a febrile illness characterized by headache, ocular pain, myalgia, and arthralgia occurred during June 1994 among Peruvian army troops in Northern Peru. On June 14-16, 1994, clinical data and blood samples were obtained from eight soldiers with a febrile illness, and from 26 others who had a history of febrile illness during the past three months. A follow-up blood sample was obtained 107 days later from four of the febrile and seven of the afebrile soldiers. Serum samples were tested for dengue (DEN), Oropouche (ORO), and Venezuelan equine encephalitis (VEE) IgM and IgG antibodies by an enzyme-linked immunosorbent assay (ELISA). Virus isolation was performed by inoculation of newborn mice and Vero cell cultures. Viral isolates were identified by immunofluorescence, ELISA, and nucleotide sequencing. A VEE virus infection was confirmed in three of the eight febrile soldiers, two by virus isolation, and one by serology. Antigenic analysis indicated that one of the virus isolates was similar to VEE subtype I, variety ID, viruses previously isolated in Colombia and Venezuela. Nucleotide sequence data showed that both viral isolates were identical to one another and closely related to VEE ID viruses previously isolated in Peru, Colombia, and Venezuela. Serologic results showed that two of 26 afebrile soldiers had IgM antibody to VEE and four had IgG antibody to VEE; two febrile soldiers had IgG antibody in their first serum samples. Oropouche-specific IgM antibody was detected in one of the eight febrile and five of the afebrile soldiers, and 18 of the 34 soldiers had low titers of ORO IgG antibody titers, which did not meet the diagnostic criteria for confirmed cases. All soldiers were negative for DEN IgM antibody, and 10 had flavivirus IgG antibody that reacted with DEN antigens. These data indicated that VEE ID virus was one of the causes of illness among Peruvians soldiers and that this was the first association of this VEE subtype with human disease in Peru.

RNA transcriptional biosignature analysis for identifying febrile infants with serious bacterial infections in the emergency department: a feasibility study.

PubMed

Mahajan, Prashant; Kuppermann, Nathan; Suarez, Nicolas; Mejias, Asuncion; Casper, Charlie; Dean, J Michael; Ramilo, Octavio

2015-01-01

To develop the infrastructure and demonstrate the feasibility of conducting microarray-based RNA transcriptional profile analyses for the diagnosis of serious bacterial infections in febrile infants 60 days and younger in a multicenter pediatric emergency research network. We designed a prospective multicenter cohort study with the aim of enrolling more than 4000 febrile infants 60 days and younger. To ensure success of conducting complex genomic studies in emergency department (ED) settings, we established an infrastructure within the Pediatric Emergency Care Applied Research Network, including 21 sites, to evaluate RNA transcriptional profiles in young febrile infants. We developed a comprehensive manual of operations and trained site investigators to obtain and process blood samples for RNA extraction and genomic analyses. We created standard operating procedures for blood sample collection, processing, storage, shipping, and analyses. We planned to prospectively identify, enroll, and collect 1 mL blood samples for genomic analyses from eligible patients to identify logistical issues with study procedures. Finally, we planned to batch blood samples and determined RNA quantity and quality at the central microarray laboratory and organized data analysis with the Pediatric Emergency Care Applied Research Network data coordinating center. Below we report on establishment of the infrastructure and the feasibility success in the first year based on the enrollment of a limited number of patients. We successfully established the infrastructure at 21 EDs. Over the first 5 months we enrolled 79% (74 of 94) of eligible febrile infants. We were able to obtain and ship 1 mL of blood from 74% (55 of 74) of enrolled participants, with at least 1 sample per participating ED. The 55 samples were shipped and evaluated at the microarray laboratory, and 95% (52 of 55) of blood samples were of adequate quality and contained sufficient RNA for expression analysis. It is possible to create a robust infrastructure to conduct genomic studies in young febrile infants in the context of a multicenter pediatric ED research setting. The sufficient quantity and high quality of RNA obtained suggests that whole blood transcriptional profile analysis for the diagnostic evaluation of young febrile infants can be successfully performed in this setting.

Risk factors for febrile urinary tract infection in children with prenatal hydronephrosis: a prospective study.

PubMed

Braga, Luis H; Farrokhyar, Forough; D'Cruz, Jennifer; Pemberton, Julia; Lorenzo, Armando J

2015-05-01

We prospectively investigated the impact of risk factors for febrile urinary tract infection in infants with postnatally confirmed prenatal hydronephrosis. Patients seen for prenatal hydronephrosis from 2010 to 2013 were prospectively followed. Those with ectopic ureters and ureteroceles, posterior urethral valves and neuropathic bladders were excluded. The primary outcome was febrile catheter specimen urinary tract infection. We performed univariate analysis of 7 a priori risk factors, including age, hydronephrosis grade (low-I or II vs high-III or IV), type (isolated hydronephrosis vs hydroureteronephrosis), continuous antibiotic prophylaxis, vesicoureteral reflux grade, gender and circumcision status. Time to febrile urinary tract infection curves analyzed by Cox proportional regression were generated to adjust for confounders. We collected data on 334 patients, of whom 78% were male. A febrile urinary tract infection developed in 65 patients (19%) at a median of 4 months (range 1 to 31). High grade hydronephrosis was present in 192 infants (57%). Continuous antibiotic prophylaxis was prescribed in 96 cases (29%). Of patients on continuous antibiotic prophylaxis 69% had high grade hydronephrosis. Vesicoureteral reflux was identified in 57 of 238 patients in whom voiding cystourethrogram was done. Reflux was grade I to III in 14 cases and grade IV or V in 43. Two-thirds of the patients with reflux were on continuous antibiotic prophylaxis. Circumcision was performed in 95 males (36%). Cox proportional regression identified female gender (HR 3.3, p = 0.02), uncircumcised males (HR 3.2, p = 0.02), hydroureteronephrosis (HR 10.9, p <0.01), vesicoureteral reflux (HR 20.8, p <0.01) and lack of continuous antibiotic prophylaxis (HR 5.2, p <0.01) as risk factors for febrile urinary tract infection. Subgroup analysis excluding vesicoureteral reflux showed that high grade prenatal hydronephrosis was also a significant risk factor (HR 3.0, p = 0.04). After patients with vesicoureteral reflux were excluded from the study, females and uncircumcised males with high grade hydroureteronephrosis had significantly higher febrile urinary tract infection rates. Therefore, those patients may benefit from continuous antibiotic prophylaxis. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Fever as an initial manifestation of spondyloarthritis: A retrospective study.

PubMed

Byun, Se Jin; Bae, William Han; Jung, Seung Min; Lee, Sang-Won; Park, Yong-Beom; Song, Jason Jungsik

2017-01-01

We aimed to evaluate a wide spectrum of clinical features of adult patients with spondyloarthritis (SpA) whose initial manifestation was fever, using the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. We retrospectively collected the electronic medical records of hospitalized SpA patients who initially presented to the Severance Hospital (Seoul, Korea) with fever from January 2010 to May 2016. As a control group, we also recruited one-hundred consecutive patients who were diagnosed with SpA in our outpatient clinic. Clinical features and laboratory findings were compared in two patient groups. There were 26 patients who had fever as initial presentation of SpA (reactive arthritis 50%, undifferentiated SpA 26.9%, ankylosing spondylitis 15.4%, enteropathic arthritis 3.8%, psoriatic arthritis 3.8%). Peripheral SpA was more common in febrile SpA patients than in control SpA patients (65.4% vs 24.0%, p<0.001). Febrile SpA patients were less frequently HLA-B27 positive than control SpA patients (52.2% vs 77.0%, p<0.05). At baseline, systemic inflammatory markers were significantly higher in the febrile SpA patients (white blood cell count, 11.57 vs 7.81 cells/μL, p<0.001; erythrocyte sedimentation rate, 69.2 vs 41.0 mm/h, p<0.001; C-reactive protein, 109.6 vs 15.3 mg/L, p<0.001). The proportion of patients treated with systemic steroids was significantly higher in febrile SpA patients (57.7% vs. 11.0%, p<0.001). The proportion of patients who visited rheumatology specialty was significantly lower in febrile SpA patients than in control SpA patients (7.7% vs 59.0%, p<0.001). Various subgroups of SpA can be presented with fever as an initial manifestation. Febrile SpA patients demonstrated higher systemic inflammation and a lower chance to visit rheumatology in early stage. When evaluating febrile patients with any clinical features of SpA, clinicians are advised to consider performing SpA-focused evaluation including HLA-B27 or a simple sacroiliac joint radiograph.

Febrile Infection-Related Epilepsy Syndrome (FIRES): An Overview of Treatment and Recent Patents.

PubMed

Hon, Kam Lun E Lun; Leung, Alexander K C; Torres, Alcy R

2018-05-08

New-onset refractory status epilepticus (NORSE) refers to a clinical presentation in a patient without active epilepsy or other existing relevant neurological disorder, with new onset of refractory status epilepticus in the absence of a clear acute or active structural, metabolic, or toxic cause. Febrile infection-related epilepsy syndrome (FIRES) is a subset of NORSE that requires a febrile infection between 24 hours and 2 weeks prior to the onset of refractory status epilepticus, with or without fever at the onset of status epilepticus, and with no restriction to the age of the patient. The literature on FIRES is scarce. This article reviews the pathophysiology, clinical features, and various treatment modalities in the treatment of FIRES. A Medline/Pubmed search was conducted using Clinical Queries with the key terms "febrile infection-related epilepsy syndrome", "FIRES", "new-onset refractory status epilepticus" and "NORSE". The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term "FIRES", "NORSE" and "febrile epilepsy syndrome" from www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com. FIRES almost invariably begins with a mild nonspecific febrile illness in an otherwise healthy individual. Twenty four hours to two weeks later, seizures begin and quickly become very frequent and worsen, becoming status epilepticus. Seizures can be simple motor, complex partial or secondary generalized. The exact etiology is no known. It is possible that the syndrome is caused by an inflammatory or autoimmune mechanism. Seizures in FIRES are notoriously very difficult to treat. Treatment modalities include, among others, various antiepileptic drugs, ketogenic diet, intravenous corticosteroids, intravenous immunoglobulin, and burst-suppression coma. Outcome is poor; most children are left with significant cognitive disability and refractory epilepsy. Recent patents for the management of FIRES are discussed. FIRES is a rare epilepsy syndrome of unclear etiology in which children, usually of school age, suddenly develop very frequent seizures after a mild febrile illness. Seizures in FIRES are typically recalcitrant and difficult to treat. The prognosis is poor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Geometric and electronic structures of silicon-sodium binary clusters. I. Ionization energy of SinNam

NASA Astrophysics Data System (ADS)

Kishi, Reiko; Iwata, Suehiro; Nakajima, Atsushi; Kaya, Koji

1997-08-01

Sodium doped silicon clusters (SinNam; 1⩽n⩽14, 1⩽m⩽5) produced by two types of laser vaporization were studied. The adsorption of Na atoms on the Sin clusters leads the substantial lowering of the ionization energy, Ei, of SinNam clusters. Their reactivity toward NO molecules was measured with a fast flow reactor, and the anticorrelation between the Eis and the reactivity was clearly observed; species having low Ei exhibit high reactivity and vice versa. Moreover, the clear parallelism between the Eis of SinNa and the EAs of Sin is found. This is consistent with the fact that the structure of SinNa clusters keeps the frame of the corresponding Sin cluster unchanged and that the electronic structure of SinNa is similar to that of the corresponding negative ion Sin-. In addition to the experimental studies, the geometries, adsorption energies, and vertical ionization energies of SinNa (n=1-7) were investigated with ab initio MO calculations including electron correlation; The Møller-Plesset perturbation theory was used and the configuration interaction (CI) calculation was carried out, particularly for a diatomic molecule, SiNa.

Specific requirement of the chromatin modifier mSin3B in cell cycle exit and cellular differentiation

PubMed Central

David, Gregory; Grandinetti, Kathryn B.; Finnerty, Patricia M.; Simpson, Natalie; Chu, Gerald C.; DePinho, Ronald A.

2008-01-01

The Sin3-histone deacetylase (HDAC) corepressor complex is conserved from yeast to humans. Mammals possess two highly related Sin3 proteins, mSin3A and mSin3B, which serve as scaffolds tethering HDAC enzymatic activity, and numerous sequence-specific transcription factors to enable local chromatin regulation at specific gene targets. Despite broad overlapping expression of mSin3A and mSin3B, mSin3A is cell-essential and vital for early embryonic development. Here, genetic disruption of mSin3B reveals a very different phenotype characterized by the survival of cultured cells and lethality at late stages of embryonic development with defective differentiation of multiple lineages—phenotypes that are strikingly reminiscent of those associated with loss of retinoblastoma family members or E2F transcriptional repressors. Additionally, we observe that, whereas mSin3B−/− cells cycle normally under standard growth conditions, they show an impaired ability to exit the cell cycle with limiting growth factors. Correspondingly, mSin3B interacts physically with the promoters of known E2F target genes, and its deficiency is associated with derepression of these gene targets in vivo. Together, these results reveal a critical role for mSin3B in the control of cell cycle exit and terminal differentiation in mammals and establish contrasting roles for the mSin3 proteins in the growth and development of specific lineages. PMID:18332431

Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

PubMed

Contreras, Valeria; Sepúlveda, Sebastián; Heredia, Ana

2016-02-24

It is still controversial if the combined use of beta-lactam antibiotics and aminoglycosides has advantages over broad-spectrum beta-lactam monotherapy for the empirical treatment of cancer patients with febrile neutropenia. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including 14 pertinent randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the combination of beta-lactam antibiotics and aminoglycosides probably does not lead to a reduced mortality in febrile neutropenic cancer patients and it might increase nephrotoxicity.

Continuous antibiotic prophylaxis reduces the risk of febrile UTI in children with asymptomatic antenatal hydronephrosis with either ureteral dilation, high-grade vesicoureteral reflux, or ureterovesical junction obstruction.

PubMed

Herz, Daniel; Merguerian, Paul; McQuiston, Leslie

2014-08-01

The efficacy and utility of continuous antibiotic prophylaxis (CAP) in children with congenital antenatal hydronephrosis (ANH) is uncertain. The literature has both supportive and contradictory evidence. The growing trend not to place children with ANH on CAP has created varied clinical practice based on anecdotal individual case characteristics. Our goal was to compare individual infant characteristics between those children who were maintained on CAP to those that were not to try to determine predisposing risk factors to febrile. All electronic medical records (EMRs) of children referred to our institution for congenital ANH over a period from 2001 to 2011 were examined. We excluded those referred for urinary tract infection (UTI) who had a history of congenital ANH. We also excluded those with incomplete records, or follow-up less than 2 years. Children were divided into two groups: those maintained on CAP (YCAP) and those not maintained on CAP (NCAP). Our primary endpoint was febrile UTI. Follow-up was at least 24 months. Demographic, perinatal and postnatal clinical data were recorded. Statistical analysis was performed using STATA Version 11.1. Of the 405 children fitting inclusion criteria, 278 (68.6%) children were maintained on CAP and 127 (31.4%) were not on CAP. The incidence of prematurity, oligohydramnios, perinatal respiratory complications, use of perinatal antibiotics, circumcision status, renal anomalies, associated medical diagnoses, and low birth weight did not differ between the two groups. Overall the incidence of febrile UTI during the follow-up period was 22.2%. The incidence of febrile UTI between the YCAP and NCAP groups was significant (YCAP = 7.9% and NCAP 18.7%, p = 0.021). Multivariate logistic regression using CAP as the dichotomous dependent variable revealed that ureteral dilation, high-grade vesicoureteral reflux (VUR), and ureterovesical junction (UVJ) obstruction were independent risk factors for febrile UTI. More specifically, children with ureteral dilation >11 mm NOT maintained on CAP had a 5.54 (OR = 5.54; CI = 3.15-7.42, p = 0.001) fold increased risk of febrile UTI compared to those maintained on CAP. The presence of ureteral dilation, high grade VUR, and UVJ obstruction were independent risk factors for development of UTI in children with congenital ANH. Therefore CAP may have a significant role in reducing the risk of febrile UTI in children with ANH with those identifiable risk factors, but otherwise seems unnecessary. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Principles, practices and knowledge of clinicians when assessing febrile children: a qualitative study in Kenya.

PubMed

Hooft, Anneka M; Ripp, Kelsey; Ndenga, Bryson; Mutuku, Francis; Vu, David; Baltzell, Kimberly; Masese, Linnet N; Vulule, John; Mukoko, Dunstan; LaBeaud, A Desiree

2017-09-20

Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment. The objective of this study was to examine the various factors that influence clinician behavior in diagnosing and managing children presenting with fever to health centres in Kenya. A total of 20 clinicians (2 paediatricians, 1 medical officer, 2 nurses, and 15 clinical officers) were interviewed, working at 5 different government-sponsored public clinic sites in two areas of Kenya where malaria is prevalent. Clinicians were interviewed one-on-one using a structured interview technique. Interviews were then analysed qualitatively for themes. The following five themes were identified: (1) Strong familiarity with diagnosis of malaria and testing for malaria; (2) Clinician concerns about community understanding of febrile illness, use of traditional medicine, delay in seeking care, and compliance; (3) Reliance on clinical guidelines, history, and physical examination to diagnose febrile illness and recognize danger signs; (4) Clinician discomfort with diagnosis of primary viral illness leading to increased use of empiric antibiotics; and (5) Lack of resources including diagnostic testing, necessary medications, and training modalities contributes to the difficulty clinicians face in assessing and treating febrile illness in children. These themes persisted across all sites, despite variation in levels of medical care. Within these themes, clinicians consistently expressed a need for reliable basic testing, especially haemograms and bacterial cultures. Clinicians discussed the use of counseling and education to improve community understanding of febrile illness in order to decrease preventable deaths in children. Results of this study suggest that since malarial testing has become more widespread, clinicians working in resource-poor environments still face difficulty when evaluating a child with fever, especially when malaria testing is negative. Improving access to additional diagnostics, continuing medical education, and ongoing evaluation and revision of clinical guidelines may lead to more consistent management of febrile illness by providers, and may potentially decrease prescription of unnecessary antibiotics. Additional interventions at the community level may also have an important role in managing febrile illness, however, more studies are needed to identify targets for intervention at both the clinic and community levels.

A hospital-based study on seroprevalence of leptospirosis among febrile cases in northeastern Malaysia.

PubMed

Rafizah, A A Noor; Aziah, B D; Azwany, Y N; Imran, M Kamarul; Rusli, A Mohamed; Nazri, S Mohd; Nikman, A Mohd; Nabilah, I; Asma', H Siti; Zahiruddin, W M; Zaliha, I

2013-06-01

To determine the seroprevalence of leptospirosis among febrile inpatient cases in northeastern Malaysia. A hospital-based cross-sectional study was conducted among 999 febrile cases admitted to 10 hospitals in northeastern Malaysia. A survey using a proforma sheet was used to obtain sociodemographic and occupational information. Serum samples were screened for leptospirosis by IgM enzyme-linked immunosorbent assay test (IgM ELISA) and confirmed by microscopic agglutination test (MAT). There was an equivalent distribution of males and females in the 999 respondents enrolled in the study. The majority were Malay (94.7%) and their mean age was 39.4 (standard deviation 17.6) years. The overall seroprevalence of leptospirosis was 8.4% (95% confidence interval (CI) 6.8-10.3) (n=84). The high-risk occupational group was found to have a higher seroprevalence, which was 56% (95% CI 45.3-66.1) (n=47). The predominant serogroup was Sejroe (82.1%, 95% CI 72.6-88.8) (n=69). This study revealed a possible high seroprevalence of leptospirosis among febrile cases, indicating the need to review the importance of adding leptospirosis to the case investigation of febrile illness, especially among high-risk occupational groups in Malaysia, as well as in other endemic countries. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Evidence that platelet-derived growth factor may be a novel endogenous pyrogen in the central nervous system.

PubMed

Pelá, I R; Ferreira, M E; Melo, M C; Silva, C A; Coelho, M M; Valenzuela, C F

2000-05-01

Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory actions in the mammalian central nervous system (CNS). Like the cytokines, PDGF primarily signals through tyrosine phosphorylation-dependent pathways that activate multiple intracellular molecules including Janus family kinases. We previously showed that microinjection of PDGF-BB into the lateral ventricle induced a febrile response in rats that was reduced by pretreatment with Win 41662, a potent inhibitor of PDGF receptors (Pelá IR, Ferreira MES, Melo MCC, Silva CAA, and Valenzuela CF. Ann NY Acad Sci 856: 289-293, 1998). In this study, we further characterized the role of PDGF-BB in the febrile response in rats. Microinjection of PDGF-BB into the third ventricle produced a dose-dependent increase in colonic temperature that peaked 3-4 h postinjection. Win 41662 attenuated fever induced by intraperitoneal injection of bacterial lipopolysaccharide, suggesting that endogenous PDGF participates in the febrile response to this exogenous pyrogen. Importantly, febrile responses induced by tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were unchanged by Win 41662. Both indomethacin and dexamethasone blocked the PDGF-BB-induced increase in colonic temperature, and, therefore, we postulate that PDGF-BB may act via prostaglandin- and/or inducible enzyme-dependent pathways. Thus our findings suggest that PDGF-BB is an endogenous CNS mediator of the febrile response in rats.

Cefepime and amikacin as empirical therapy in patients with febrile neutropaenia: a single-centre phase II prospective survey.

PubMed

Mebis, J; Vandeplassche, S; Goossens, H; Berneman, Z N

2009-01-01

The aim of the survey was to prospectively evaluate the effectiveness of the combination therapy cefepime and amikacin in the initial treatment of haematology patients with febrile neutropaenia. Two hundred twenty (220) episodes of febrile neutropaenia were analysed in 54 males and 82 females (median age 58 years), most patients had a severe neutropaenia with in 72% of all periods a neutrophil count of less than 100. Microbiological infection was confirmed in 72 cases (32.8%). Sixty-one (61) bacteria were isolated from blood cultures of which 22 were identified as Gram-negative bacteria and 38 as Gram-positive bacteria. Sixty-three (63) episodes (28.6%) were clinically documented, 85 episodes (38.6%) were fever of unknown origin. Clinical cure was achieved in 123 febrile episodes (56%) after initiation of the current antibiotic protocol; another 22 patients (10%) became afebrile after modifying the initial antibiotic regimen 48 hours or longer after treatment initiation. In 61 cases (27.7%) there was persistent fever or re-occurrence of fever, these cases were considered as treatment failure. Eight patients (3.6%) died during the study. This survey has demonstrated that the combination therapy with cefepime and amikacin can be considered as an effective treatment for febrile neutropaenia in high-risk haematological patients in our centre with a high incidence of resistance to Gram-negative bacteria.

Prevalence and predictors of urinary tract infection and severe malaria among febrile children attending Makongoro health centre in Mwanza city, North-Western Tanzania

PubMed Central

2012-01-01

Background In malaria endemic areas, fever has been used as an entry point for presumptive treatment of malaria. At present, the decrease in malaria transmission in Africa implies an increase in febrile illnesses related to other causes among underfives. Moreover, it is estimated that more than half of the children presenting with fever to public clinics in Africa do not have a malaria infection. Thus, for a better management of all febrile illnesses among under-fives, it becomes relevant to understand the underlying aetiology of the illness. The present study was conducted to determine the relative prevalence and predictors of P. falciparum malaria, urinary tract infections and bacteremia among under-fives presenting with a febrile illness at the Makongoro Primary Health Centre, North-Western Tanzania. Methods From February to June 2011, a cross-sectional analytical survey was conducted among febrile children less than five years of age. Demographic and clinical data were collected using a standardized pre-tested questionnaire. Blood and urine culture was done, followed by the identification of isolates using in-house biochemical methods. Susceptibility patterns to commonly used antibiotics were investigated using the disc diffusion method. Giemsa stained thin and thick blood smears were examined for any malaria parasites stages. Results A total of 231 febrile under-fives were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10-25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had urinary tract infections, P. falciparum malaria and bacteremia respectively. In general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and only one child had all three infections. Predictors of urinary tract infections (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of P. falciparum severe malaria were pallor (OR = 4.66 95%CI, 1.21-17.8, P = 0.025) and convulsion (OR = 102, 95% CI, 10-996, P = 0.001). Escherichia coli were the common gram negative isolates from urine (72.3%, 95% CI, 66.50-78.10) and blood (40%, 95%CI, and 33.70-46.30). Escherichia coli from urine were 100% resistant to ampicillin, 97% resistant to co-trimoxazole, 85% resistant to augmentin and 32.4% resistant to gentamicin; and they were 100%, 91.2% and 73.5% sensitive to meropenem, ciprofloxacin and ceftriaxone respectively. Conclusion Urinary tract infection caused by multi drug resistant Escherichia coli was the common cause of febrile illness in our setting. Improvement of malaria diagnosis and its differential diagnosis from other causes of febrile illnesses may provide effective management of febrile illnesses among children in Tanzania PMID:22958592

Prevalence and predictors of urinary tract infection and severe malaria among febrile children attending Makongoro health centre in Mwanza city, North-Western Tanzania.

PubMed

Msaki, Bahati P; Mshana, Stephen E; Hokororo, Adolfina; Mazigo, Humphrey D; Morona, Domenica

2012-03-16

In malaria endemic areas, fever has been used as an entry point for presumptive treatment of malaria. At present, the decrease in malaria transmission in Africa implies an increase in febrile illnesses related to other causes among underfives. Moreover, it is estimated that more than half of the children presenting with fever to public clinics in Africa do not have a malaria infection. Thus, for a better management of all febrile illnesses among under-fives, it becomes relevant to understand the underlying aetiology of the illness. The present study was conducted to determine the relative prevalence and predictors of P. falciparum malaria, urinary tract infections and bacteremia among under-fives presenting with a febrile illness at the Makongoro Primary Health Centre, North-Western Tanzania. From February to June 2011, a cross-sectional analytical survey was conducted among febrile children less than five years of age. Demographic and clinical data were collected using a standardized pre-tested questionnaire. Blood and urine culture was done, followed by the identification of isolates using in-house biochemical methods. Susceptibility patterns to commonly used antibiotics were investigated using the disc diffusion method. Giemsa stained thin and thick blood smears were examined for any malaria parasites stages. A total of 231 febrile under-fives were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10-25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had urinary tract infections, P. falciparum malaria and bacteremia respectively. In general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and only one child had all three infections. Predictors of urinary tract infections (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of P. falciparum severe malaria were pallor (OR = 4.66 95%CI, 1.21-17.8, P = 0.025) and convulsion (OR = 102, 95% CI, 10-996, P = 0.001). Escherichia coli were the common gram negative isolates from urine (72.3%, 95% CI, 66.50-78.10) and blood (40%, 95%CI, and 33.70-46.30). Escherichia coli from urine were 100% resistant to ampicillin, 97% resistant to co-trimoxazole, 85% resistant to augmentin and 32.4% resistant to gentamicin; and they were 100%, 91.2% and 73.5% sensitive to meropenem, ciprofloxacin and ceftriaxone respectively. Urinary tract infection caused by multi drug resistant Escherichia coli was the common cause of febrile illness in our setting. Improvement of malaria diagnosis and its differential diagnosis from other causes of febrile illnesses may provide effective management of febrile illnesses among children in Tanzania.

The Spinal Instability Neoplastic Score: Impact on Oncologic Decision-Making.

PubMed

Versteeg, Anne L; Verlaan, Jorrit-Jan; Sahgal, Arjun; Mendel, Ehud; Quraishi, Nasir A; Fourney, Daryl R; Fisher, Charles G

2016-10-15

Systematic literature review. To address the following questions in a systematic literature review: 1. How is spinal neoplastic instability defined or classified in the literature before and after the introduction of the Spinal Instability Neoplastic Score (SINS)? 2. How has SINS affected daily clinical practice? 3. Can SINS be used as a prognostic tool? Spinal neoplastic-related instability was defined in 2010 and simultaneously SINS was introduced as a novel tool with criteria agreed upon by expert consensus to assess the degree of spinal stability. PubMed, Embase, and clinical trial databases were searched with the key words "spinal neoplasm," "spinal instability," "spinal instability neoplastic score," and synonyms. Studies describing spinal neoplastic-related instability were eligible for inclusion. Primary outcomes included studies describing and/or defining neoplastic-related instability, SINS, and studies using SINS as a prognostic factor. The search identified 1414 articles, of which 51 met the inclusion criteria. No precise definition or validated assessment tool was used specific to spinal neoplastic-related instability prior to the introduction of SINS. Since the publication of SINS in 2010, the vast majority of the literature regarding spinal instability has used SINS to assess or describe instability. Twelve studies specifically investigated the prognostic value of SINS in patients who underwent radiotherapy or surgery. No consensus could be determined regarding the definition, assessment, or reporting of neoplastic-related instability before introduction of SINS. Defining spinal neoplastic-related instability and the introduction of SINS have led to improved uniform reporting within the spinal neoplastic literature. Currently, the prognostic value of SINS is controversial. N/A.

Clozapine-Induced Febrile Neutropenia and Cellulitis.

PubMed

Yaylaci, Selcuk; Yilmaz, Emine Ulku; Guclu, Ertugrul; Kumsar, Neslihan Akkisi; Tamer, Ali; Karabay, Oguz

2014-03-01

Clozapine is one of the atypical antipsychotics and is frequently prescribed to patients with treatment-resistant schizophrenia. Agranulocytosis is a major side effect that may lead to death, which limits its use. This is a case report of a patient that developed febrile neutropenia and cellulitis after treatment with clozapine for 20 weeks.

Efficient replication, and evolution of Sindbis virus genomes with non-canonical 3'A/U-rich elements (NC3ARE) in neonatal mice.

PubMed

James, Frederick D; Hietala, Katie A; Eldar, Dganit; Guess, Tiffany E; Cone, Cecil; Mundell, Nathan A; Mundall, Nathan; Barnett, Joey V; Raju, Ramaswamy

2007-12-01

Sindbis virus (SIN) is a mosquito-transmitted animal RNA virus. We previously reported that SIN genomes lacking a canonical 19 nt 3'CSE undergo novel repair processes in BHK cells to generate a library of stable atypical SIN genomes with non-canonical 3'A/U-rich elements (NC3AREs) adjacent to the 3' poly(A) tail [1]. To determine the stability and evolutionary pressures on the SIN genomes with NC3AREs to regain a 3'CSE, five representative SIN isolates and a wild type SIN were tested in newborn mice. The key findings of this study are: (a) all six SIN isolates, including those that have extensive NC3AREs in the 3'NTRs, replicate well and produce high titer viremia in newborn mice; (b) 7-9 successive passages of these isolates in newborn mice produced comparable levels of viremia; (c) while all isolates produced only small-sized plaques during primary infection in animals, both small- and large-sized plaques were generated in all other passages; (d) polymerase stuttering occurs on select 3' oligo(U) motifs to add more U residues within the NC3AREs; (e) the S3-8 isolate with an internal UAUUU motif in the 3'poly(A) tail maintains this element even after 9 passages in animals; (f) despite differences in 3'NTRs and variable tissue distribution, all SIN isolates appear to produce similar tissue pathology in infected animals. Competition experiments with wt SIN and atypical SIN isolates in BHK cells show dominance of wt SIN. As shown for BHK cells in culture, the 3'CSE of the SIN genome is not required for virus replication and genome stability in live animals. Since the NC3AREs of atypical SIN genomes are not specific to SIN replicases, alternate RNA motifs of alphavirus genome must confer specificity in template selection. These studies fulfill the need to confirm the long-term viability of atypical SIN genomes in newborn mice and offer a basis for exploring the use of atypical SIN genomes in biotechnology.

Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.

PubMed

Lee, Yee Mei; Lang, Dora; Lockwood, Craig

Increasing numbers of studies identify new prognostic factors for categorising chemotherapy-induced febrile neutropenia adult cancer patients into high- or low-risk groups for adverse outcomes. These groupings are used to tailor therapy according to level of risk. However many emerging factors with prognostic significance remain controversial, being based on single studies only. A systematic review was conducted to determine the strength of association of all identified factors associated with the outcomes of chemotherapy-induced febrile neutropenia patients. The participants included were adults of 15 years old and above, with a cancer diagnosis and who underwent cancer treatment.The review focused on clinical factors and their association with the outcomes of cancer patients with chemotherapy-induced febrile neutropenia at presentation of fever.All quantitative studies published in English which investigated clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia were considered.The primary outcome of interest was to identify the clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia. Electronic databases searched from their respective inception date up to December 2011 include MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Science-Direct, Scopus and Mednar. The quality of the included studies was subjected to assessment by two independent reviewers. The standardised critical appraisal tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used to assess the following criteria: representativeness of study population; clearly defined prognostic factors and outcomes; whether potential confounders were addressed and appropriate statistical analysis was undertaken for the study design. Data extraction was performed using a modified version of the standardised extraction tool from the JBI-MAStARI. Prognostic factors and the accompanying odds ratio reported for the significance of these factors that were identified by multivariate regression, were extracted from each included study. Studies results were pooled in statistical meta-analysis using Review Manager 5.1. Where statistical pooling was not possible, the findings were presented in narrative form. Seven studies (four prospective cohort and three retrospective cohort) investigating 22 factors in total were included. Fixed effects meta-analysis showed: hypotension [OR=1.66, 95%CI, 1.14-2.41, p=0.008] and thrombocytopenia [OR=3.92, 95%CI, 2.19-7.01, p<0.00001)] were associated with high-risk of adverse outcomes for febrile neutropenia. Other factors that were statistically significant from single studies included: age of patients, clinical presentation at fever onset, presence or absence of co-morbidities, infections, duration and severity of neutropenia state. Five prognostic factors failed to demonstrate an association between the variables and the outcomes measured and they include: presence of pneumonia, total febrile days, median days to fever, recovery from neutropenia and presence of moderate clinical symptoms in association with Gram-negative bacteraemia. Despite the overall limitations identified in the included studies, this review has provided a synthesis of the best available evidence for the prognostic factors used in risk stratification of febrile neutropenia patients. However, the dynamic aspects of prognostic model development, validation and utilisation have not been addressed adequately thus far. Given the findings of this review, it is timely to address these issues and improve the utilisation of prognostic models in the management of febrile neutropenia patients. The identified factors are similar to the factors in current prognostic models. However, additional factors that were reported to be statistically significant in this review (thrombocytopenia, presence of central venous catheter, and duration and severity of neutropenia) have not previously been included in prognostic models. This review has found these factors may improve the performance of current models by adding or replacing some of the factors. The role of risk stratification of chemotherapy-induced febrile neutropenia patients continues to evolve as the practice of risk-based therapy has been demonstrated to be beneficial to patients, clinicians and health care organisations. Further research to identify new factors /markers is needed to develop a new model which is reliable and accurate for these patients, regardless of cancer types. A robust and well-validated prognostic model is the key to enhance patient safety in the risk-based management of cancer patients with chemotherapy-induced febrile neutropenia.

[Food matching based on herbal properties of formulas in "Treatise on Febrile Diseases"].

PubMed

Yan, Su-rong; Zheng, Hu-zhan; Miao, Su-fen; Wang, Yun

2015-09-01

Based on databases for herbal properties of formulas and foods recorded in "Treatise on Febrile Diseases", a case study was conducted for the food matching method according to herbal properties of formulas in "Treatise on Febrile Diseases". The result show that the method was technically feasible once the herbal properties of foods were determined. Moreover, according to herbal properties of target formulas, the compositions of foods were effectively defined. In this study, researchers determined the similarity between the food matching scheme and the target formulas in function and efficacy, provided a quantitative method for food formulation and promote the development of application technology of the herbal property theory and the compatibility theory.

Augmented Currents of an HCN2 Variant in Patients with Febrile Seizure Syndromes

PubMed Central

Dibbens, Leanne M.; Reid, Christopher A.; Hodgson, Bree; Thomas, Evan A.; Phillips, Alison M.; Gazina, Elena; Cromer, Brett A.; Clarke, Alison L.; Baram, Tallie Z.; Scheffer, Ingrid E.; Berkovic, Samuel F.; Petrou, Steven

2012-01-01

The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were ~35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential contributor to polygenic epilepsy. PMID:20437590

Development and validation of the Single Item Narcissism Scale (SINS).

PubMed

Konrath, Sara; Meier, Brian P; Bushman, Brad J

2014-01-01

The narcissistic personality is characterized by grandiosity, entitlement, and low empathy. This paper describes the development and validation of the Single Item Narcissism Scale (SINS). Although the use of longer instruments is superior in most circumstances, we recommend the SINS in some circumstances (e.g. under serious time constraints, online studies). In 11 independent studies (total N = 2,250), we demonstrate the SINS' psychometric properties. The SINS is significantly correlated with longer narcissism scales, but uncorrelated with self-esteem. It also has high test-retest reliability. We validate the SINS in a variety of samples (e.g., undergraduates, nationally representative adults), intrapersonal correlates (e.g., positive affect, depression), and interpersonal correlates (e.g., aggression, relationship quality, prosocial behavior). The SINS taps into the more fragile and less desirable components of narcissism. The SINS can be a useful tool for researchers, especially when it is important to measure narcissism with constraints preventing the use of longer measures.

Serological evidence of rift valley fever virus among acute febrile patients in Southern Mozambique during and after the 2013 heavy rainfall and flooding: implication for the management of febrile illness.

PubMed

Gudo, Eduardo Samo; Pinto, Gabriela; Weyer, Jacqueline; le Roux, Chantel; Mandlaze, Arcildo; José, Américo Feriano; Muianga, Argentina; Paweska, Janusz Tadeusz

2016-06-08

Rift Valley fever virus (RVFV) remains heavily neglected in humans in Mozambique, even though recent outbreaks were reported in neighboring countries in humans and several cases of RVFV in cattle were reported in several districts in Mozambique. We conducted a cross sectional study during and after severe flooding that occurred in 2013 in Mozambique. Paired acute and convalescent serum samples were tested from febrile patients attending a primary health care unit in a suburban area of Maputo city for the presence of IgG and IgM antibodies against Rift Valley fever virus (RVFV) using enzyme-linked immunosorbent assay (ELISA). Seroconversion of IgG anti-RVFV was observed in 5 % (10/200) of convalescent patients and specific IgM anti-RVFV was detected in one acute patient (0.5 %; 1/200). All sera from acute patient tested negative by real time PCR. In conclusion, our results suggest that RVF represent an important but neglected cause of febrile illness following periods of flooding in southern Mozambique.

Technical report—Diagnosis and management of an initial UTI in febrile infants and young children.

PubMed

Finnell, S Maria E; Carroll, Aaron E; Downs, Stephen M

2011-09-01

The diagnosis and management of urinary tract infections (UTIs) in young children are clinically challenging. This report was developed to inform the revised, evidence-based, clinical guideline regarding the diagnosis and management of initial UTIs in febrile infants and young children, 2 to 24 months of age, from the American Academy of Pediatrics Subcommittee on Urinary Tract Infection. The conceptual model presented in the 1999 technical report was updated after a comprehensive review of published literature. Studies with potentially new information or with evidence that reinforced the 1999 technical report were retained. Meta-analyses on the effectiveness of antimicrobial prophylaxis to prevent recurrent UTI were performed. Review of recent literature revealed new evidence in the following areas. Certain clinical findings and new urinalysis methods can help clinicians identify febrile children at very low risk of UTI. Oral antimicrobial therapy is as effective as parenteral therapy in treating UTI. Data from published, randomized controlled trials do not support antimicrobial prophylaxis to prevent febrile UTI when vesicoureteral reflux is found through voiding cystourethrography. Ultrasonography of the urinary tract after the first UTI has poor sensitivity. Early antimicrobial treatment may decrease the risk of renal damage from UTI. Recent literature agrees with most of the evidence presented in the 1999 technical report, but meta-analyses of data from recent, randomized controlled trials do not support antimicrobial prophylaxis to prevent febrile UTI. This finding argues against voiding cystourethrography after the first UTI.

Revelation of Brugada electrocardiographic pattern during a febrile state associated with acute myocardial infarction.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-09-24

The prevalence of the Brugada-type ECG and its natural history are still unclear. The Brugada syndrome is usually identified by a characteristic Brugada-type ECG that consists of ST elevation of a coved type in the precordial leads V1 to V3 and ventricular fibrillation that can lead to sudden cardiac death, although affected individuals may have a normal ECG. Mutations in the cardiac sodium channel gene SCN5A, which encodes the alpha-subunit of the human cardiac voltage-dependent Na+ channel (Na(v)1.5), are identified in 15-30% of patients with Brugada syndrome. Most SCN5A mutations lead to a 'loss-of-function' phenotype, reducing the Na+ current during the early phases of the action potential. Several nongenetic factors have been mentioned in the literature as possible inductors of the ECG pattern resembling Brugada syndrome. As such, a Brugada-type ECG may appear in some patients during febrile states and in those who are under the influence of cocaine and pharmaceutical drugs that have a sodium channel-blocking effect. It has been also reported chest pain and ST elevation Brugada pattern during febrile states. We present a case of revelation of Brugada pattern in a 69-year-old Italian man during a febrile state associated with acute myocardial infarction. Also this report confirms that Brugada pattern should be considered as one of differential diagnoses when we examine the patients during a febrile state. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study.

PubMed

Atladóttir, Hjördis Ósk; Henriksen, Tine Brink; Schendel, Diana E; Parner, Erik T

2012-12-01

Results of animal studies suggest that maternal immune activation during pregnancy causes deficiencies in fetal neurodevelopment. Infectious disease is the most common path to maternal immune activation during pregnancy. The goal of this study was to determine the occurrence of common infections, febrile episodes, and use of antibiotics reported by the mother during pregnancy and the risk for autism spectrum disorder (ASD) and infantile autism in the offspring. We used a population-based cohort consisting of 96 736 children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on infection, febrile episodes, and use of antibiotics was self-reported through telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and infantile autism were retrieved from the Danish Psychiatric Central Register; 976 children (1%) from the cohort were diagnosed with ASD. Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism. Our results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for ASD/infantile autism. The results may be due to multiple testing; the few positive findings are potential chance findings.

Validation of MASCC Score for Risk Stratification in Patients of Hematological Disorders with Febrile Neutropenia.

PubMed

Taj, M; Nadeem, M; Maqsood, S; Shah, T; Farzana, T; Shamsi, T S

2017-09-01

The purpose of this study is to evaluate the association of MASCC score (Multinational Association for Supportive Care in Cancer Score) in patients with febrile neutropenia (as resultant treatment of hematological disorders) for risk assessment of morbidity and mortality. Patients presenting with Febrile Neutropenia from November 2011 till December 2013 were enrolled in the study. Initially all patients were hospitalized and their MASCC score was calculated, however those with high risk stayed in hospital till full ANC recovery while low risk group was discharged earlier and keenly followed as out-patient while being on prophylactic oral antibiotics. The MASCC risk-index score was calculated and patients with risk score >21 were regarded as low-risk while <21 were labeled as high-risk. On the basis of 226 febrile neutropenia patient 132(58.4 %) were categorized as low risk while 94(41.5 %) as high risk patients according to MASCC risk index score. In low risk group 123(93 %) had uncomplicated infection while 9(7 %) had complicated infections. There was no mortality documented in low risk group while eight patients died in high risk group. In this study we correctly predicted outcome of 123(93 %) low risk group patients. The study had positive predictive value of 93 % with both sensitivity and specificity of 65 and 75 % respectively. The MASCC risk score is a valuable tool in determining the outcome in patients with febrile neutropenia.

Risk factors of leptospirosis among febrile hospital admissions in northeastern Malaysia.

PubMed

Rafizah, A A Noor; Aziah, B D; Azwany, Y N; Imran, M Kamarul; Rusli, A Mohamed; Nazri, S Mohd; Nikman, A Mohd; Nabilah, I; Asma', H Siti; Zahiruddin, W M; Zaliha, I

2013-01-01

Leptospirosis is a worldwide zoonotic disease. Risk factors for the disease may vary among countries. This study was conducted to determine the risk factors of leptospirosis among febrile cases. A hospital-based cross-sectional study was conducted among 999 febrile patients admitted to 10 hospitals in northeastern Malaysia, from August 2010 to February 2011. An interviewer-guided proforma sheet on sociodemography, type of occupation and social history data was distributed to all adult patients with fever on admission. Serum sample for leptospirosis was screened by IgM Enzyme-linked Immunosorbent Assay (IgM ELISA) test and confirmed by Microscopic Agglutination Test (MAT). The cut-off point for positive MAT was ≥ 1:400 titer in single acute specimens. Seroprevalence of leptospirosis was 8.4% (95% CI: 6.8, 10.3) (n=84/999) by MAT. Multiple logistic regression analysis showed that the high risk occupation group (OR: 1.95, 95% CI: 1.22, 3.13) (p=0.005) and history of recent recreational activity (OR: 2.36, 95% CI: 1.46, 3.85) (p<0.001) were significant associated factors for leptospirosis. This study shows a relatively high seroprevalence of leptospirosis in northeastern Malaysia. Identification of high risk occupational group and history of recent recreational activity will help to increase the index of suspicion to diagnose leptospirosis among febrile inpatients due to its mimicking other common febrile illnesses in Malaysia. Copyright © 2013 Elsevier Inc. All rights reserved.

Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study.

PubMed

Söderman, Martina; Rhedin, Samuel; Tolfvenstam, Thomas; Rotzén-Östlund, Maria; Albert, Jan; Broliden, Kristina; Lindblom, Anna

2016-01-01

Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0-18 years, being treated at a children's oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher's exact test and Mann-Whitney U test were used for group comparisons. At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9-74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.

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

Inhibition of polyomavirus ori-dependent DNA replication by mSin3B.

PubMed

Xie, An-Yong; Folk, William R

2002-12-01

When tethered in cis to DNA, the transcriptional corepressor mSin3B inhibits polyomavirus (Py) ori-dependent DNA replication in vivo. Histone deacetylases (HDACs) appear not to be involved, since tethering class I and class II HDACs in cis does not inhibit replication and treating the cells with trichostatin A does not specifically relieve inhibition by mSin3B. However, the mSin3B L59P mutation that impairs mSin3B interaction with N-CoR/SMRT abrogates inhibition of replication, suggesting the involvement of N-CoR/SMRT. Py large T antigen interacts with mSin3B, suggesting an HDAC-independent mechanism by which mSin3B inhibits DNA replication.

Prevalence of Lassa Virus Disease (LVD) in Nigerian children with fever or fever and convulsions in an endemic area.

PubMed

Akhuemokhan, Odigie C; Ewah-Odiase, Rosemary O; Akpede, Nosa; Ehimuan, Jacqueline; Adomeh, Donatus I; Odia, Ikpomwonsa; Olomu, Sylvia C; Pahlmann, Meike; Becker-Ziaja, Beate; Happi, Christian T; Asogun, Danny A; Okogbenin, Sylvanus A; Okokhere, Peter O; Dawodu, Osagie S; Omoike, Irekpono U; Sabeti, Pardis C; Günther, Stephan; Akpede, George O

2017-07-01

Convulsions with fever in children are a common neurologic emergency in the tropics, and determining the contribution of endemic viral infections can be challenging. In particular, there is a dearth of data on the prevalence and clinical differentiation of Lassa virus disease (LVD) in febrile children in endemic areas of Nigeria, which has multiple lineages of the virus. The aim of this study was to determine the prevalence and presentation of LVD in febrile children with and without convulsions. This was a prospective study of consecutive febrile children aged ≥1 month- 15 years admitted to the Children's Emergency Room of Irrua Specialist Teaching Hospital over a period of 1 year. Febrile children with convulsions (Cases) were compared with those without convulsions (Controls). LVD was defined by the presence of a positive Lassa virus RT-PCR test. Rates were compared between groups using χ2 or Fisher's exact tests and p <0.05 taken as significant. 373 (40.9%) of 913 admissions had fever. Of these, 108/373 (29%) presented with convulsions. The overall prevalence of LVD was 13/373 (3.5%; 95% CI = 1.9%, 5.7%) in febrile admissions, 3/108 (2.8%) in Cases and 10/265 (3.8%) in Controls [(Odds Ratio (95% Confidence Interval) (OR (95% CI)) of LVD in Cases versus Controls = 0.73 (0.2, 2.7)]. Only vomiting (OR (95% CI) = 0.09 (0.01, 0.70)) and bleeding (OR (95% CI) = 39.56 (8.52, 183.7)) were significantly associated with an increased prevalence of LVD. LVD is an important cause of fever, including undifferentiated fever in children in endemic areas, but it is not significantly associated with convulsions associated with fever. Its prevalence, and lack of clinical differentiation on presentation, underscores the importance of a high index of suspicion in diagnosis. Screening of febrile children with undifferentiated fever in endemic areas for LVD could be an important medical and public health control measure.

Euthermic Endocarditis

PubMed Central

DeSimone, Daniel C.; Baddour, Larry M.; Lahr, Brian D.; Chung, Heath H.; Wilson, Walter R.; Steckelberg, James M.

2013-01-01

Background Most patients with infective endocarditis (IE) manifest fever. Comparison of endocarditis patients with and without fever, and whether the lack of fever in IE is a marker for poorer outcomes, such as demonstrated in other severe infectious diseases, have not been defined. Methods and Results Cases from the Mayo Clinic, Rochester, Minnesota, Division of Infectious Diseases IE registry, a single-center database that contains all cases of IE treated at our center. Diagnosis date between 1970 and 2006, which met the modified Duke criteria for definite endocarditis, without fever was included. There were 240 euthermic endocarditis cases included in this analysis, with 282 febrile controls selected by frequency matching on gender and decade of diagnosis. Euthermic patients had a median age of 63.6 years (±16.1) as compared to 59.0 years (±16.4) in the febrile control group (p=0.001). Median (IQR) symptom duration prior to diagnosis was 4.0 (1.0, 12.0) weeks in the euthermic group compared to 3.0 (1.0, 8.0) weeks in the febrile controls (p= 0.006). From unadjusted analyses, survival rates were 87% in euthermic cases versus 83% in febrile controls across 28-day follow-up (p=0.164), and 72% in euthermic group cases versus 69% in febrile controls across 1-year follow-up (p=0.345). Also unadjusted, the 1-year cumulative incidence rate of valve surgery was higher in euthermic cases versus febrile controls (50% vs. 39%, p= 0.004). Conclusions Patients with euthermic endocarditis are older, and lack of fever was associated with longer symptom duration and delayed diagnosis prior to IE diagnosis. Despite a higher unadjusted rate of valve surgery in euthermic patients, the result was not significant when adjusting for baseline confounders. Differences in survival rates at both 28-days and 365-days were not statistically significant between the two groups. PMID:24244630

Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007.

PubMed

Forshey, Brett M; Guevara, Carolina; Laguna-Torres, V Alberto; Cespedes, Manuel; Vargas, Jorge; Gianella, Alberto; Vallejo, Efrain; Madrid, César; Aguayo, Nicolas; Gotuzzo, Eduardo; Suarez, Victor; Morales, Ana Maria; Beingolea, Luis; Reyes, Nora; Perez, Juan; Negrete, Monica; Rocha, Claudio; Morrison, Amy C; Russell, Kevin L; Blair, Patrick J; Olson, James G; Kochel, Tadeusz J

2010-08-10

Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public health relevance, little is know about the geographic distribution, relative impact, and risk factors for arbovirus infection in many regions of the world. Our objectives were to describe the arboviruses associated with acute undifferentiated febrile illness in participating clinics in four countries in South America and to provide detailed epidemiological analysis of arbovirus infection in Iquitos, Peru, where more extensive monitoring was conducted. A clinic-based syndromic surveillance system was implemented in 13 locations in Ecuador, Peru, Bolivia, and Paraguay. Serum samples and demographic information were collected from febrile participants reporting to local health clinics or hospitals. Acute-phase sera were tested for viral infection by immunofluorescence assay or RT-PCR, while acute- and convalescent-phase sera were tested for pathogen-specific IgM by ELISA. Between May 2000 and December 2007, 20,880 participants were included in the study, with evidence for recent arbovirus infection detected for 6,793 (32.5%). Dengue viruses (Flavivirus) were the most common arbovirus infections, totaling 26.0% of febrile episodes, with DENV-3 as the most common serotype. Alphavirus (Venezuelan equine encephalitis virus [VEEV] and Mayaro virus [MAYV]) and Orthobunyavirus (Oropouche virus [OROV], Group C viruses, and Guaroa virus) infections were both observed in approximately 3% of febrile episodes. In Iquitos, risk factors for VEEV and MAYV infection included being male and reporting to a rural (vs urban) clinic. In contrast, OROV infection was similar between sexes and type of clinic. Our data provide a better understanding of the geographic range of arboviruses in South America and highlight the diversity of pathogens in circulation. These arboviruses are currently significant causes of human illness in endemic regions but also have potential for further expansion. Our data provide a basis for analyzing changes in their ecology and epidemiology.

Febrile Convulsion among Hospitalized Children Aged Six Months to Five Years and Its Association With Haemoglobin Electrophoretic Pattern.

PubMed

Adeboye, M; Ojuawo, A; Adeniyi, A; Ibraheem, R M; Amiwero, C

2015-07-01

Febrile convulsion and sickle cell disease are common in tropical countries and both are associated with significant morbidity and mortality. Worldwide, Nigeria has the highest prevalence of sickle cell disease. However, there is a dearth of knowledge on the haemoglobin electrophoresis in patients with febrile convulsions. This was a hospital based, descriptive, cross-sectional study of the relationship between haemoglobin genotype and febrile convulsion at the University of Ilorin Teaching Hospital over a period of 12 months. A self-designed pretested questionnaire was administered on the subjects, and necessary examinations and investigations were conducted. Of a total of 1675 children admitted into the emergency paediatric unit during the study period, children aged 6 months-5 years that presented with febrile convulsions were 167(10%). Of this, 1,212 were aged 6 months-5 years. Thus, the age specific, hospital-based prevalence was 13.8%. The M:F was 1.1:1. Their Haemoglobin genotype distribution was AA 131(78.4%), AS 23(13.8%), AC 6(3.6%), SS 6(3.6%), and 1(0.6%) SC. The mean age of the sickle cell disease patients was higher at 46.0±13.5 months compared to 29.2±15.4 months in the non-sickle cell disease patients (p=0.005). The mean packed cell volume in subjects with sickle cell anaemia was 8.8±1.5%; the only case of haemoglobin SC had packed cell volume of 20%, while the non-sickle cell disease patients had a normal PCV. Malaria was present in 80.4% of them. Febrile convulsion remains a common cause of hospitalisation. It is uncommon in haemoglobin SS where severe anaemia is always an accompanying derangement. The packed cell volume is nearly normal in children with normal haemoglobin genotype.

Risk of Bacterial Meningitis in Children 6 to 11 Months of Age With a First Simple Febrile Seizure: A Retrospective, Cross-sectional, Observational Study.

PubMed

Guedj, Romain; Chappuy, Hélène; Titomanlio, Luigi; Trieu, Thanh-Van; Biscardi, Sandra; Nissack-Obiketeki, Gisèle; Pellegrino, Béatrice; Charara, Oussama; Angoulvant, François; Villemeur, Thierry Billette De; Levy, Corinne; Cohen, Robert; Armengaud, Jean Baptiste; Carbajal, Ricardo

2015-11-01

National and international guidelines are very heterogeneous about the necessity to perform a lumbar puncture (LP) in children under 12 months of age with a first simple febrile seizure. We estimated the risk of bacterial meningitis in children aged 6 to 11 months with a first simple febrile seizure. This multicenter retrospective study was conducted in seven pediatric emergency departments (EDs) in the region of Paris, France. Visits of patients aged 6 to 11 months for a first simple febrile seizure from January 2007 to December 2011 were analyzed. Bacterial meningitis was sequentially sought for by 1) analyzing bacteriologic data at the time of the visit, 2) looking for data from a second visit to the hospital after the index visit, and 3) phone calling the child's parents to determine the symptom evolution after the index visit. Infants lost to this follow-up were searched for in a national bacterial meningitis database. From a total of 1,183,487 visits in the seven pediatric EDs, 116,503 were for children 6 to 11 months of age. From these, 205 visits were for a first simple febrile seizure. An LP was performed in 61 patients (29.8%). The outcome bacterial meningitis was ascertainable for 168 (82%) visits. No bacterial meningitis was found among these patients (95% confidence interval = 0% to 2.2%). None of the 37 infants lost to our follow-up were registered in the national database as having bacterial meningitis. Among children between 6 and 11 months of age with a first simple febrile seizure, the risk of bacterial meningitis is extremely low. These results should encourage national and international societies to either develop or endorse guidelines limiting routine LP in these infants and contribute to widely homogenized management practices. © 2015 by the Society for Academic Emergency Medicine.

[An unusual cause of febrile neutropenia: brucellosis].

PubMed

Solmaz, Soner; Asma, Süheyl; Ozdoğu, Hakan; Yeral, Mahmut; Turunç, Tuba

2014-10-01

Febrile neutropenia which is a common complication of cancer treatment, is one of the major causes of morbidity and mortality. Several gram-negative and gram-positive bacteria are responsible for infections in neutropenic patients, however the most common microorganisms are Escherichia coli and coagulase-negative staphylococci, in decreasing order. Although Brucella spp. infections are endemic in Turkey, brucellosis-related febrile neutropenia has only rarely been reported. In this report, a case of brucellosis-related febrile neutropenia in a patient with acute myeloblastic leukemia (AML) was presented. A 56-year-old male patient presenting with fever, petechiae/purpura, leukocytosis, thrombocytopenia, and anemia was admitted to our hospital. Laboratory studies revealed a hemoglobin level of 8.27 g/dl, leukocyte count of 77.100 k/ml, absolute neutrophil count of 200 k/ml, and platelets at 94.200 k/ml. The patient was diagnosed as AML-M1 and piperacillin/tazobactam was started as the first-line antibiotic therapy due to the febrile neutropenia. On admission, blood and urine cultures were negative. Once the fever was controlled, remission/induction chemotherapy was initiated. However, fever developed again on the eight day, and vancomycin was added to the therapy. Since the fever persisted, the antibiotic therapy was gradually replaced with meropenem and linezolid. However, fever continued and the patient's general condition deteriorated. Subsequently performed Brucella tube agglutination test revealed positivity at 1/320 titer and the microorganism grown in blood culture (Bactec 9050; BD, USA) was identified as B.melitensis by conventional methods. Rifampicin and doxycycline therapy was started immediately, however, the patient died due to septic shock. If the tests for brucellosis were performed earlier when response to second step antibiotic therapy lacked in this patient, it was assumed that mortality could be prevented by the prompt initiation of the appropriate treatment. Thus, since brucellosis is endemic in Turkey, it should be considered as a possible agent of febrile neutropenia especially in patients unresponsive to empiric antibiotherapy and appropriate diagnostic tests should be performed.

Febrile urinary tract infections after ureteroneocystostomy and subureteral injection of dextranomer/hyaluronic acid for vesicoureteral reflux--do choice of procedure and success matter?

PubMed

Dwyer, Moira E; Husmann, Douglas A; Rathbun, Suzanne R; Weight, Christopher J; Kramer, Stephen A

2013-01-01

Despite success rates favoring ureteroneocystostomy over subureteral injection of dextranomer/hyaluronic acid for correction of vesicoureteral reflux, the reported incidence of postoperative febrile urinary tract infection favors the latter. We evaluated contemporary treatment cohorts for an association between correction of vesicoureteral reflux and risk of postoperative febrile urinary tract infection. We retrospectively reviewed the records of 396 consecutive patients who underwent ureteroneocystostomy or subureteral injection of dextranomer/hyaluronic acid between 1994 and 2008. Time to event multivariate analyses included preoperative grade of vesicoureteral reflux and bladder/bowel dysfunction. Of 316 patients meeting study criteria 210 underwent ureteroneocystostomy (356 ureters) and 106 underwent subureteral injection of dextranomer/hyaluronic acid (167). Median patient age was 5.7 years (IQR 3.4 to 8.3). Median followup was 28 months (IQR 8 to 61). Ureteral success was significantly greater after ureteroneocystostomy (88%, 314 of 356 cases) vs subureteral injection of dextranomer/hyaluronic acid (74%, 124 of 167, p = 0.0001). When controlling for preoperative grade of vesicoureteral reflux and bladder/bowel dysfunction, the risk of persistent reflux was 2.8 times greater after subureteral injection of dextranomer/hyaluronic acid (95% CI 1.7-4.7, p <0.0001). The incidence of febrile urinary tract infection did not significantly differ between ureteroneocystostomy (8%, 16 of 210 cases) and subureteral injection of dextranomer/hyaluronic acid (4%, 4 of 106; HR 1.96, 95% CI 0.64-5.9, p = 0.24) even when controlling for preoperative grade of vesicoureteral reflux, a predictor of postoperative febrile urinary tract infection on multivariate analysis (HR 2.2 per increase in grade, 95% CI 1.3-3.6, p = 0.0022). Persistent reflux was not a predictor of postoperative febrile urinary tract infection (HR 0.81, 95% CI 0.22-2.9, p = 0.75 for ureteroneocystostomy vs HR 1.8, 95% CI 0.2-17.3, p = 0.6 for subureteral injection of dextranomer/hyaluronic acid and HR 1.8, 95% CI 0.3-3.3, p = 0.6 for both). The incidence of postoperative febrile urinary tract infection may be independent of radiographic procedural success. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

History and Outcome of Febrile Neutropenia Outside the Oncology Setting: A Retrospective Study of 76 Cases Related to Non-Chemotherapy Drugs

PubMed Central

Andrès, Emmanuel; Mourot-Cottet, Rachel; Maloisel, Frédéric; Keller, Olivier; Vogel, Thomas; Séverac, François; Tebacher, Martine; Gottenberg, Jacques-Eric; Weber, Jean-Christophe; Kaltenbach, Georges; Goichot, Bernard; Sibilia, Jean; Korganow, Anne-Sophie; Herbrecht, Raoul

2017-01-01

Background: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital. Patients and methods: Data from 76 patients with idiosyncratic drug-induced febrile neutropenia were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis conducted at the Strasbourg University Hospital (Strasbourg, France). Results: Mean patient age was 52.2 years old (range: 18–93) and gender ratio (F/M) 1.6, with several comorbidities present in 86.8% of patients. The most common causative drugs were: antibiotics (37.4%), antithyroid drugs (17.2%), neuroleptic and anti-epileptic agents (13.1%), non-steroidal anti-inflammatory agents and analgesics (8%), and platelet aggregation inhibitors (8%). Main clinical presentations upon hospitalization included isolated fever (30%), sore throat, acute tonsillitis and sinusitis (18.4%), documented pneumonia (18.4%), septicemia (14.5%), and septic shock (6.6%). Mean neutrophil count at nadir was 0.13 × 10(9)/L (range: 0–0.48). While in hospital, 22 patients (28.9%) worsened clinically and required intensive care unit placement. All patients were promptly treated with broad-spectrum antibiotics, and 45 (59.2%) with hematopoietic growth factors. Mean duration of hematological recovery (neutrophil count ≥1.5 × 10(9)/L) was 7.5 days (range: 2–21), which was reduced to 0.7 days (range: 2–16) (p = 0.089) with hematopoietic growth factors. Outcome was favorable in 89.5% of patients, whereas eight died. Conclusions: Like in oncology and myelosuppressive chemotherapy settings, idiosyncratic febrile neutropenia is typically serious, about 40% of patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of “daily medication” exposure. PMID:28954408

Anxiety and coping in women with breast cancer in chemotherapy.

PubMed

Silva, Araceli Vicente da; Zandonade, Eliana; Amorim, Maria Helena Costa

2017-06-05

to identify the coping strategies used by women with breast cancer in chemotherapy and to verify the association with the anxiety profile presented by them. cross-sectional study of the analytical type. We used a random sample of 307 women with cancer in previous chemotherapy, adjuvant or palliative treatment. The data was collected using an interview technique with form registration, active search in medical records, Scale of Mode of Confronting Problems and Inventory of Anxiety and State. The Statistical Package for Social Sciences 19.0, Pearson correlation coefficient and the test Mann-Whitney were used. there was a significant association of the anxiety trait and problem-focused coping strategies with a focus on emotion (p<0,000) and the anxiety state with problem-focused coping (p=0,001) and with focus on emotion (p=0,004). The results demonstrate weak associations between different coping strategies. the coping strategy chosen by women with breast cancer is directly related to anxiety. Patients with low-level anxiety tend to use problem-solving strategies while emotion-focused coping is applied if the level is medium to high. identificar as estratégias de enfrentamento utilizadas por mulheres com câncer de mama em quimioterapia e verificar a associação com o perfil de ansiedade por elas apresentado. estudo de corte transversal do tipo analítico. Utilizou-se amostra aleatória de 307 mulheres com câncer em tratamento quimioterápico prévio, adjuvante ou paliativo. Coletou-se os dados com técnica de entrevista com registro em formulário, busca ativa nos prontuários, Escala de Modo de Enfrentamento de Problemas e Inventário de Ansiedade e Estado. Utilizou-se para análise o Pacote Estatístico para Ciências Sociais 19.0, coeficiente de correlação de Pearson e o teste Mann-Whitney. existiu associação significante do traço de ansiedade e as estratégias de enfrentamento com foco no problema e com foco na emoção (p<0,000) e o estado de ansiedade com o enfrentamento com foco no problema (p=0,001) e com o foco na emoção (p=0,004). Os resultados demonstram fracas associações entre as diferentes estratégias de enfrentamento. a estratégia de enfrentamento eleita pelas mulheres com câncer de mama tem relação direta com a ansiedade. As pacientes que possuem ansiedade com nível baixo tendem a utilizar como estratégia a resolução dos problemas e quando o nível é médio a alto o enfrentamento com foco na emoção. identificar las estrategias de enfrentamiento utilizadas por las mujeres con cáncer de mama sometidas a quimioterapia y la asociación con el perfil de la ansiedad que presentan. estudio transversal de tipo analítico. Utilizamos muestra aleatoria de 307 mujeres con cáncer con quimioterapia previa, adyuvante o paliativa. Se recogieron los datos con entrevistas registradas en un formulario y búsqueda activa en los registros médicos, Escala de Modo de Enfrentamiento de Problemas e Inventario de Ansiedad y Estado. Se utilizó para análisis el Paquete Estadístico para Ciencias Sociales 19.0, coeficiente de correlación Pearson y la prueba de Mann-Whitney. hubo una asociación significativa del rasgo ansiedad y las estrategias de enfrentamiento centradas en el problema y en la emoción (p<0,000) y el estado de ansiedad con el enfrentamiento centrado en el problema (p=0,001) y con el foco en emoción (p=0,004). Los resultados muestran asociaciones débiles entre diferentes estrategias de enfrentamiento. la estrategia de enfrentamiento elegida por las mujeres con cáncer de mama está directamente relacionada con la ansiedad. Las pacientes que tienen ansiedad con niveles bajos tienden a utilizar una estrategia de solución de problemas y cuando el nivel es medio a alto utilizan el enfrentamiento centrado en la emoción.

Diagnosis and Management of Borrelia turicatae Infection in Febrile Soldier, Texas, USA

PubMed Central

Pietralczyk, Elizabeth; Lopez, Job E.; Brooks, Christopher; Schriefer, Martin E.; Wozniak, Edward; Stermole, Benjamin

2017-01-01

In August 2015, a soldier returned from field exercises in Texas, USA, with nonspecific febrile illness. Culture and sequencing of spirochetes from peripheral blood diagnosed Borrelia turicatae infection. The patient recovered after receiving doxycycline. No illness occurred in asymptomatic soldiers potentially exposed to the vector tick and prophylactically given treatment. PMID:28418310

Outcomes of febrile children presumed to be immunocompetent who present with leukopenia or neutropenia to an ambulatory setting.

PubMed

Serwint, J R; Dias, M M; Chang, H; Sharkey, M; Walker, A R

2005-09-01

To determine significant medical outcomes in febrile children presenting to an ambulatory setting with neutropenia and/or leukopenia. Retrospective medical record review conducted on febrile patients who had a blood culture drawn, with white blood cell counts less than 5,000/mm3 and/or an absolute neutrophil count less than 1000/mm3. Ninety-one patients were identified; 5 with positive blood culture results, 13 with significant non-oncologic disease, and 3 patients with leukemia who had involvement of 2 or more cell lines. In the majority of patients, clinical judgment, physical findings, and review of all cell lines of the complete blood cell count identified those with significant disease.

Sinomenine inhibits lipopolysaccharide-induced inflammatory injury by regulation of miR-101/MKP-1/JNK pathway in keratinocyte cells.

PubMed

Liu, Shumei; Man, Yigang; Zhao, Li

2018-05-01

Recent studies have demonstrated that Sinomenine (SIN) exerted anti-inflammatory effect in various immune-related diseases. However, the effect of SIN on glucocorticoids dermatitis has not been investigated. In our study, we aimed to explore the effect of SIN on lipopolysaccharide (LPS)-induced inflammatory injury in HaCaT cells. We constructed an inflammatory injury model of LPS-induced HaCaT cells, then SIN was added to LPS-treated cells, cell viability, apoptosis, apoptosis-associated factors and inflammatory cytokines were detected by CCK-8, flow cytometry, western blot, qRT-PCR and ELISA. Subsequently, miR-101 mimic and mimic control were transfected into HaCaT cells to investigate the effect of SIN and miR-101 on LPS-induced cells injury. Furthermore, MKP-1 and JNK signal pathways were measured by qRT-PCR and western blot. Finally, the animal experiment was performed to further clarify the effect of SIN on inflammatoty injury. LPS suppressed cell viability, promoted apoptosis and increased IL-6, IL-8 and TNF-α expressions and secretions in HaCaT cells. SIN significantly alleviated LPS-induced HaCaT cells injury. Additionally, SIN down-regulated miR-101 expression, and the protective effect of SIN on LPS-induced inflammatory injury was abolished by miR-101 overexpression. Besides, SIN promoted MKP-1 expression by down-regulation of miR-101, and SIN inhibited JNK signal pathway by up-regulation of MKP-1 expression in LPS-treated HaCaT cells. Animal experiments revealed that SIN exhibited anti-inflammatory effects in vivo. The data indicated that SIN attenuated LPS-induced inflammatory injury by regulation of miR-101, MKP-1 and JNK pathway. These findings might provide a novel method for treatment of glucocorticoids dermatitis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Development and Validation of the Single Item Narcissism Scale (SINS)

PubMed Central

Konrath, Sara; Meier, Brian P.; Bushman, Brad J.

2014-01-01

Main Objectives The narcissistic personality is characterized by grandiosity, entitlement, and low empathy. This paper describes the development and validation of the Single Item Narcissism Scale (SINS). Although the use of longer instruments is superior in most circumstances, we recommend the SINS in some circumstances (e.g. under serious time constraints, online studies). Methods In 11 independent studies (total N = 2,250), we demonstrate the SINS' psychometric properties. Results The SINS is significantly correlated with longer narcissism scales, but uncorrelated with self-esteem. It also has high test-retest reliability. We validate the SINS in a variety of samples (e.g., undergraduates, nationally representative adults), intrapersonal correlates (e.g., positive affect, depression), and interpersonal correlates (e.g., aggression, relationship quality, prosocial behavior). The SINS taps into the more fragile and less desirable components of narcissism. Significance The SINS can be a useful tool for researchers, especially when it is important to measure narcissism with constraints preventing the use of longer measures. PMID:25093508

IN GRAMMAR'S FALL, WE SINNED ALL.

ERIC Educational Resources Information Center

TIBBETTS, A.M.

THROUGH THEIR LOSS OF FAITH IN TRADITIONAL GRAMMAR, MEN HAVE "SINNED" AND CONTRIBUTED SLIGHTLY BUT IMPORTANTLY TO THE CREATION OF AN AMORAL AND RELATIVISTIC SOCIETY. PROMPTED BY THE SIN OF INTELLECTUAL PRIDE, SOME LINGUISTS SEEM TO ASSUME THAT GRAMMATICAL PROBLEMS CAN BE SOLVED BY RATIOCINATION ALONE. IGNORANCE OF THE PAST--ANOTHER SIN--AND…

Risk factors and outcomes of afebrile bacteremia patients in an emergency department.

PubMed

Yo, Chia-Hung; Lee, Meng-Tse Gabriel; Hsein, Yenh-Chen; Lee, Chien-Chang

2016-12-01

There is limited research on afebrile bacteremia. We aimed to compare the risk factors and outcomes of patients with afebrile and febrile infections. This was a retrospective cohort study of bloodstream isolates from 994 adults admitted to the emergency department of a university hospital. Afebrile infections, defined as the absence of fever history or measured fever through the emergency department course, was compared with febrile infection. Frequencies and proportions of sources of infection, comorbidities, along with organ failure and mortality were presented. The major outcome measure was 30-day survival. chi-Square or Student's t test was used for univariate analysis, and Cox proportional hazard model was used for multivariate analysis. We found that the risk factors and outcomes of febrile and afebrile bacteremia patients were very different. The afebrile patients were older, have higher Charlson comorbidity index, and had poorer outcomes than the febrile patients. We also found that oldest old age, nonhematologic malignancy, necrotizing fasciitis, spontaneous bacterial peritonitis, and pneumonia were each positive independent predictors of afebrile bacteremia, whereas Escherichia coli infection and liver abscess were independent negative predictors of afebrile bacteremia. Finally, the 30-day all-cause mortality was higher in the afebrile group than in the febrile group (45% versus 12%, log-rank P<0.001). This series of patients with afebrile bacteremia confirmed the previously reported associations with old age and immunocompromised conditions. Clinicians should explore the possibility of occult severe infection, and initiate early hemodynamic support and empirical antimicrobial therapy for patients with the aforementioned risk factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost and radiation exposure in the workup of febrile pediatric urinary tract infections.

PubMed

Michaud, Jason E; Gupta, Natasha; Baumgartner, Timothy S; Kim, Brian; Bosemani, Thangamadhan; Wang, Ming-Hsien

2016-06-15

Technetium-99m dimercaptosuccinic acid (DMSA) scans are often used in the evaluation of pediatric patients with febrile urinary tract infections (UTIs). Given the prevalence of febrile UTIs, we sought to quantify the cost, radiation exposure, and clinical utility of DMSA scans when compared with dedicated pediatric renal ultrasounds (RUSs). An institutional review board approved retrospective study of children under the age of 18 years evaluated at our institution for febrile UTIs between the years 2004-2013 was conducted. The patients had to meet all of the following inclusion criteria: a diagnosis of vesicoureteral reflux, a fever >38°C, a positive urine culture, and evaluation with a DMSA scan and RUS. A chart review was used to construct a cost analysis of technical and professional fees, radiographic results, and radiation dose equivalents. Overall, 104 children met the inclusion criteria. A total of 122 RUS and 135 DMSA scans were performed. The technical costs of a DMSA scan incurred a 35% cost premium as compared to an RUS. The average effective radiation dose of a single DMSA scan was 2.84 mSv. New radiographic findings were only identified on 7% of those patients who underwent greater than 1 DMSA scan. The utility of the unique information acquired from a DMSA scan as compared to a RUS in the evaluation of febrile UTI must be evaluated on an individual case-by-case basis given the increased direct costs and radiation exposure to the patient. Copyright © 2016 Elsevier Inc. All rights reserved.

Are clinical, laboratory, and imaging markers suitable predictors of vesicoureteral reflux in children with their first febrile urinary tract infection?

PubMed

Mahyar, Abolfazl; Ayazi, Parviz; Mavadati, Shiva; Oveisi, Sonia; Habibi, Morteza; Esmaeily, Shiva

2014-08-01

This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38℃, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2℃ and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. This study revealed fever>38.2℃ and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux.

Are Clinical, Laboratory, and Imaging Markers Suitable Predictors of Vesicoureteral Reflux in Children With Their First Febrile Urinary Tract Infection?

PubMed Central

Ayazi, Parviz; Mavadati, Shiva; Oveisi, Sonia; Habibi, Morteza; Esmaeily, Shiva

2014-01-01

Purpose This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. Materials and Methods One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. Results Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38℃, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2℃ and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. Conclusions This study revealed fever>38.2℃ and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux. PMID:25132949

Office-based treatment and outcomes for febrile infants with clinically diagnosed bronchiolitis.

PubMed

Luginbuhl, Lynn M; Newman, Thomas B; Pantell, Robert H; Finch, Stacia A; Wasserman, Richard C

2008-11-01

The goals were to describe the (1) frequency of sepsis evaluation and empiric antibiotic treatment, (2) clinical predictors of management, and (3) serious bacterial illness frequency for febrile infants with clinically diagnosed bronchiolitis seen in office settings. The Pediatric Research in Office Settings network conducted a prospective cohort study of 3066 febrile infants (<3 months of age with temperatures >or=38 degrees C) in 219 practices in 44 states. We compared the frequency of sepsis evaluation, parenteral antibiotic treatment, and serious bacterial illness in infants with and without clinically diagnosed bronchiolitis. We identified predictors of sepsis evaluation and parenteral antibiotic treatment in infants with bronchiolitis by using logistic regression models. Practitioners were less likely to perform a complete sepsis evaluation, urine testing, and cerebrospinal fluid culture and to administer parenteral antibiotic treatment for infants with bronchiolitis, compared with those without bronchiolitis. Significant predictors of sepsis evaluation in infants with bronchiolitis included younger age, higher maximal temperature, and respiratory syncytial virus testing. Predictors of parenteral antibiotic use included initial ill appearance, age of <30 days, higher maximal temperature, and general signs of infant distress. Among infants with bronchiolitis (N = 218), none had serious bacterial illness and those with respiratory distress signs were less likely to receive parenteral antibiotic treatment. Diagnoses among 2848 febrile infants without bronchiolitis included bacterial meningitis (n = 14), bacteremia (n = 49), and urinary tract infection (n = 167). In office settings, serious bacterial illness in young febrile infants with clinically diagnosed bronchiolitis is uncommon. Limited testing for bacterial infections seems to be an appropriate management strategy.

Two-Step Process for ED UTI Screening in Febrile Young Children: Reducing Catheterization Rates.

PubMed

Lavelle, Jane M; Blackstone, Mercedes M; Funari, Mary Kate; Roper, Christine; Lopez, Patricia; Schast, Aileen; Taylor, April M; Voorhis, Catherine B; Henien, Mira; Shaw, Kathy N

2016-07-01

Urinary tract infection (UTI) screening in febrile young children can be painful and time consuming. We implemented a screening protocol for UTI in a high-volume pediatric emergency department (ED) to reduce urethral catheterization, limiting catheterization to children with positive screens from urine bag specimens. This quality-improvement initiative was implemented using 3 Plan-Do-Study-Act cycles, beginning with a small test of the proposed change in 1 ED area. To ensure appropriate patients received timely screening, care teams discussed patient risk factors and created patient-specific, appropriate procedures. The intervention was extended to the entire ED after providing education. Finally, visual cues were added into the electronic health record, and nursing scripts were developed to enlist family participation. A time-series design was used to study the impact of the 6-month intervention by using a p-chart to determine special cause variation. The primary outcome measure for the study was defined as the catheterization rate in febrile children ages 6 to 24 months. The ED reduced catheterization rates among febrile young children from 63% to <30% over a 6-month period with sustained results. More than 350 patients were spared catheterization without prolonging ED length of stay. Additionally, there was no change in the revisit rate or missed UTIs among those followed within the hospital's network. A 2-step less-invasive process for screening febrile young children for UTI can be instituted in a high-volume ED without increasing length of stay or missing cases of UTI. Copyright © 2016 by the American Academy of Pediatrics.

Investigating febrile UTI in infants: is a cystogram necessary?

PubMed

Soccorso, G; Wagstaff, J; Blakey, K; Moss, G D; Broadley, P; Roberts, J P; Godbole, P

2010-04-01

Current imaging recommendations for investigating any infantile febrile urinary tract infection (UTI) are ultrasound scan (US), micturating cystourethrogram (MCUG) and dimercaptosuccinic acid (DMSA) scan. The aim of this retrospective cohort study was to determine the need and indications for MCUG in the investigation of a first febrile infantile UTI, as doubts have been raised over its benefit. Information on 427 infants who had undergone US, MCUG and DMSA following a first febrile UTI was prospectively recorded. The infants were divided into two groups: A (354) with normal renal US and B (73) with abnormal US. DMSA findings were correlated with findings on MCUG. Main outcome measures were incidence of recurrent UTIs, change in management or intervention as a result of MCUG, and outcome at discharge. Only 21/354 (6%) infants in Group A had both scarring on DMSA and vesicoureteric reflux (VUR), predominantly low-grade on MCUG. In Group B (abnormal US), 23/73 (32%) had scarring on DMSA and vesicoureteric reflux, predominantly high grade on MCUG. Of the infants with non-scarred kidneys, 73% had dilating reflux. Successful conservative treatment was performed in 423 infants, and 4 infants in Group B required surgery. We recommend US and DMSA in all infantile febrile UTI cases. Where US is normal, MCUG should be reserved for those cases with abnormal DMSA. Where US is abnormal, MCUG should be performed irrespective of findings on DMSA scan. A randomized prospective study is necessary to evaluate this further. Copyright © 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Recent Studies on the Care of First Febrile Urinary Tract Infection in Infants and Children for the Pediatric Hospitalist.

PubMed

Sutton, Ashley G; Chandler, Nicole; Roberts, Kenneth B

2017-01-01

Urinary Tract Infection (UTI) is a common cause of bacterial infection in young children, and accounts for a significant number of pediatric hospitalizations. To review recent publications focusing on the care of children hospitalized with their first febrile UTI. A PubMed search was performed including publications from 2011-2016 on first febrile UTI in childhood. Abstracts were reviewed for being relevant to the care of hospitalized children and their follow-up. Relevant articles underwent full review by all authors and articles excluded from results included those without novel data analysis, primary improvement-based reports and studies with poor design or analysis. Included articles were categorized as "diagnosis", "management", "imaging" or "follow-up". Of 406 articles initially identified, 40 studies were included. One technical report with a systematic review was also included. Major topics addressed included the role of urinalysis in screening for UTI, use of parenteral antimicrobial therapy, the role of antimicrobial prophylaxis in prevention of recurrent UTI, and ideal follow-up and imaging approach following diagnosis of febrile UTI. Recent literature on first febrile UTI addresses a broad range of areas regarding the care of hospitalized children, though some questions remain unanswered. Overall, studies support increased attention to the potential risks, expense and invasiveness of various approaches for evaluation. Proposed updates to practice included: utilization of urinalysis for screening and diagnosis, transitioning to oral antimicrobials based on clinical improvement and limiting the routine use of voiding cystourethrogram and antimicrobial prophylaxis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Medication management of febrile children: a qualitative study on pharmacy employees' experiences.

PubMed

Stakenborg, Jacqueline P G; de Bont, Eefje G P M; Peetoom, Kirsten K B; Nelissen-Vrancken, Marjorie H J M G; Cals, Jochen W L

2016-10-01

Background While fever is mostly self-limiting, antibiotic prescription rates for febrile children are high. Although every parent who receives a prescription visits a pharmacy, we have limited insight into pharmacy employees' experiences with these parents. Pharmacy employees do however exert an important role in ensuring children receive correct dosages and in advising parents on administration of antibiotics. Objective To describe pharmacists' and pharmacy assistants' experiences with parents contacting a pharmacy for their febrile child, and to identify ways of improving medication management of these children. Setting Community pharmacies in the Netherlands. Method A qualitative study including 24 Dutch pharmacy employees was conducted, performing four focus group discussions among pharmacy employees. Analysis was based on constant comparative technique using open and axial coding. Main outcome measure Pharmacy employees' experiences with parents contacting a pharmacy for their febrile child. Results Three categories were identified: (1) workload and general experience, (2) inconsistent information on antibiotic prescriptions, (3) improving communication and collaboration. Pharmacy employees experienced that dosing errors in antibiotic prescriptions occur frequently and doctors provide inconsistent information on prescriptions. Consequently, they have to contact doctors, resulting in a higher workload for both stakeholders. They believe this can be improved by providing the indication for antibiotics on prescriptions, especially when deviating from standard dosages. Conclusion Pharmacy employees experience a high amount of dosing errors in paediatric antibiotic prescriptions. Providing the indication for antibiotics in febrile children on prescriptions, especially when deviating from standard dosages, can potentially reduce dosage errors and miscommunication between doctors and pharmacy employees.

The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia.

PubMed

Miedema, Karin G E; de Bont, Eveline S J M; Elferink, Rob F M Oude; van Vliet, Michel J; Nijhuis, Claudi S M Oude; Kamps, Willem A; Tissing, Wim J E

2011-10-01

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced gastrointestinal mucositis. Plasma was obtained from pediatric oncology patients at presentation with febrile neutropenia (n = 43) and 24-48 h later (n = 17). The patients were classified as having or not having a bacterial infection. Plasma was also obtained of patients in the absence and in the presence of mucositis (n = 26). At presentation with febrile neutropenia, median IL-8 and PCT levels were significantly increased in patients with a bacterial infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for the early detection of bacterial infection, in combination with clinical parameters or PCT the sensitivity reached 100%. After 24-48 h, only PCT was significantly elevated during bacterial infection. IL-8 levels were significantly increased during mucositis. Mucositis did not cause considerable changes in PCT levels. IL-8 is the most useful marker for the early detection of bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination with clinical parameters or PCT might be even more useful. Gastrointestinal mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and therefore, PCT might be more useful for the detection of bacterial infections during mucositis than IL-8.

A de-escalation protocol for febrile neutropenia cases and its impact on carbapenem resistance: A retrospective, quasi-experimental single-center study.

PubMed

Alshukairi, Abeer; Alserehi, Haleema; El-Saed, Aiman; Kelta, Mouhammed; Rehman, Jalil U; Khan, Farrukh A; Alsalmi, Hanadi; Alattas, Majda; Aslam, Muhammad

2016-01-01

Our objective was to evaluate the impact of using an imipenem de-escalation protocol for empiric febrile neutropenia on the development of carbapenem resistance. A pre-post intervention design was used. The intervention was adopting the imipenem de-escalation approach, which began on January 1, 2012. A retrospective chart review of cases of febrile neutropenia bacteremia was performed one year before and one year after the intervention. We compared the development of carbapenem resistance between the two study periods. Seventy-five episodes of febrile neutropenia bacteremia were included in the study. They had similar demographics, clinical features and outcomes. There were 78 and 12 pathogens in the primary and follow-up blood cultures, respectively. Approximately 61% and 66% of the primary and follow-up blood cultures, respectively, were gram-negative bacteria with similar carbapenem resistance profiles in the two study periods. In our study population, 57% of the gram-negative bacteria were ESBL pathogens. The resistance of the gram-negative bacteria to piperacillin/tazobactam (72% versus 53%, p=0.161), imipenem (16% versus 11%, p=0.684), and meropenem (8% versus 16%, p=0.638) did not significantly change after our policy change. In conclusion, the use of the carbapenem de-escalation approach for febrile neutropenia in our institution was not associated with an increase in carbepenem resistance. Future prospective multi-center studies are recommended to further confirm the current findings. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Safety of early discharge for low-risk patients with febrile neutropenia: a multicenter randomized controlled trial.

PubMed

Talcott, James A; Yeap, Beow Y; Clark, Jack A; Siegel, Robert D; Loggers, Elizabeth Trice; Lu, Charles; Godley, Paul A

2011-10-20

Febrile neutropenia commonly complicates cancer chemotherapy. Outpatient treatment may reduce costs and improve patient comfort but risk progression of undetected medical problems. By using our validated algorithm, we identified medically stable inpatients admitted for febrile neutropenia (neutrophils < 500/μL) after chemotherapy and randomly assigned them to continued inpatient antibiotic therapy or early discharge to receive identical antibiotic treatment at home. Our primary outcome was the occurrence of any serious medical complication, defined as evidence of medical instability requiring urgent medical attention. We enrolled 117 patients with 121 febrile neutropenia episodes before study termination for poor accrual. We excluded five episodes as ineligible and three because of inadequate documentation of the study outcome. Treatment groups were clinically similar, but sociodemographic imbalances occurred because of block randomization. The median presenting absolute neutrophil count was 100/μL. Hematopoietic growth factors were used in 38% of episodes. The median neutropenia duration was 4 days (range, 1 to 15 days). Five outpatients were readmitted to the hospital. Major medical complications occurred in five episodes (8%) in the hospital arm and four (9%) in the home arm (95% CI for the difference, -10% to 13%; P = .56). No study patient died. Patient-reported quality of life was similar on both arms. We found no evidence of adverse medical consequences from home care, despite a protocol designed to detect evidence of clinical deterioration. These results should reassure clinicians who elect to treat rigorously characterized low-risk patients with febrile neutropenia in suitable outpatient settings with appropriate surveillance for unexpected clinical deterioration.

Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study

PubMed Central

Söderman, Martina; Rhedin, Samuel; Tolfvenstam, Thomas; Rotzén-Östlund, Maria; Albert, Jan; Broliden, Kristina; Lindblom, Anna

2016-01-01

Objective Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. Study design Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0–18 years, being treated at a children’s oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher’s exact test and Mann-Whitney U test were used for group comparisons. Results At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9–74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. Conclusion The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts. PMID:27309354

Two cases of Kawasaki disease presented with acute febrile jaundice.

PubMed

Kaman, Ayşe; Aydın-Teke, Türkan; Gayretli-Aydın, Zeynep Gökçe; Öz, Fatma Nur; Metin-Akcan, Özge; Eriş, Deniz; Tanır, Gönül

2017-01-01

Kawasaki disease is an acute, systemic vasculitis of unknown etiology. Although gastrointestinal involvement does not belong to the classic diagnostic criteria; diarrhea, abdominal pain, hepatic dysfunction, hydrops of gallbladder, and acute febrile cholestatic jaundice are reported in patients with Kawasaki disease. We describe here two cases presented with fever, and acute jaundice as initial features of Kawasaki disease.

Effect of protein malnutrition on salmonellosis and fever.

PubMed Central

Bradley, S F; Kauffman, C A

1988-01-01

Protein-malnourished rats had greater numbers of bacteria in their livers and spleens compared with numbers in control rats following a sublethal intraperitoneal dose of Salmonella typhimurium. However, the febrile responses of both groups of rats to infection were similar. The ability to mount a normal febrile response does not necessarily reflect the ability of the host to contain an infection. PMID:3346070

High seroprevalence of antibodies against spotted fever and scrub typhus bacteria in patients with febrile Illness, Kenya.

PubMed

Thiga, Jacqueline W; Mutai, Beth K; Eyako, Wurapa K; Ng'ang'a, Zipporah; Jiang, Ju; Richards, Allen L; Waitumbi, John N

2015-04-01

Serum samples from patients in Kenya with febrile illnesses were screened for antibodies against bacteria that cause spotted fever, typhus, and scrub typhus. Seroprevalence was 10% for spotted fever group, <1% for typhus group, and 5% for scrub typhus group. Results should help clinicians expand their list of differential diagnoses for undifferentiated fevers.

Prediction of vesicoureteral reflux after a first febrile urinary tract infection in children: validation of a clinical decision rule.

PubMed

Leroy, S; Marc, E; Adamsbaum, C; Gendrel, D; Bréart, G; Chalumeau, M

2006-03-01

To test the reproducibility of a highly sensitive clinical decision rule proposed to predict vesicoureteral reflux (VUR) after a first febrile urinary tract infection in children. This rule combines clinical (family history of uropathology, male gender, young age), biological (raised C reactive protein), and radiological (urinary tract dilation on renal ultrasound) predictors in a score, and provides 100% sensitivity. A retrospective hospital based cohort study included all children, 1 month to 4 years old, with a first febrile urinary tract infection. The sensitivities and specificities of the rule at the two previously proposed score thresholds (< or =0 and < or =5) to predict respectively, all-grade or grade > or =3 VUR, were calculated. A total of 149 children were included. VUR prevalence was 25%. The rule yielded 100% sensitivity and 3% specificity for all-grade VUR, and 93% sensitivity and 13% specificity for grade > or =3 VUR. Some methodological weaknesses explain this lack of reproducibility. The reproducibility of the previously proposed decision rule was poor and its potential contribution to clinical management of children with febrile urinary tract infection seems to be modest.

Prediction of vesicoureteral reflux after a first febrile urinary tract infection in children: validation of a clinical decision rule

PubMed Central

Leroy, S; Marc, E; Adamsbaum, C; Gendrel, D; Bréart, G; Chalumeau, M

2006-01-01

Aims To test the reproducibility of a highly sensitive clinical decision rule proposed to predict vesicoureteral reflux (VUR) after a first febrile urinary tract infection in children. This rule combines clinical (family history of uropathology, male gender, young age), biological (raised C reactive protein), and radiological (urinary tract dilation on renal ultrasound) predictors in a score, and provides 100% sensitivity. Methods A retrospective hospital based cohort study included all children, 1 month to 4 years old, with a first febrile urinary tract infection. The sensitivities and specificities of the rule at the two previously proposed score thresholds (⩽0 and ⩽5) to predict respectively, all‐grade or grade ⩾3 VUR, were calculated. Results A total of 149 children were included. VUR prevalence was 25%. The rule yielded 100% sensitivity and 3% specificity for all‐grade VUR, and 93% sensitivity and 13% specificity for grade ⩾3 VUR. Some methodological weaknesses explain this lack of reproducibility. Conclusions The reproducibility of the previously proposed decision rule was poor and its potential contribution to clinical management of children with febrile urinary tract infection seems to be modest. PMID:15890693

Urinary tract infection in febrile under five children in Enugu, South Eastern Nigeria.

PubMed

Ibeneme, C A; Oguonu, T; Okafor, H U; Ikefuna, A N; Ozumba, U C

2014-01-01

Fever is a common symptom of urinary tract infection (UTI) in children less than 5 years of age. Little attention is however paid to UTI as a cause of fever in this age group. The objective of the following study is to determine the prevalence of UTI in febrile children less than 5 years of age and relate it to demographic and clinical characteristics. Urine specimen of febrile children aged 1-59 months obtained by suprapubic or midstream methods were analyzed using standard laboratory methods of microscopy, culture and sensitivity. A total of 200 children were enrolled; nearly 56% (112/200) were males. The mean age of the subjects was 31.14 ± 17.96 months. The prevalence of UTI was 11% and was significantly higher in females than in males ( P = 0.049). Children below 12 months of age had a higher rate of UTI than those 12 months and above ( P = 0.028). The common clinical features were vomiting, abdominal pain, diarrhea, urinary frequency and urgency but none had a significant association with UTI. UTI is common in febrile under-fives especially among females and infants. No association was apparent between the occurrence of UTI and clinical parameters.

Mold colonization of fiberglass insulation of the air distribution system: effects on patients with hematological malignancies.

PubMed

Takuma, Takahiro; Okada, Kaoru; Yamagata, Akihiro; Shimono, Nobuyuki; Niki, Yoshihito

2011-02-01

We investigated mold colonization of air handling units (AHUs) of heating, ventilating, and air conditioning (HVAC) systems and its effects, including invasive pulmonary mycoses and febrile neutropenia, in patients with hematological malignancies. Sample collection with transparent adhesive tape and culture swabs revealed that AHUs were heavily colonized with molds, including thermotolerant, variously distributed Penicillium spp. Cases of nosocomial invasive pulmonary mycosis were not clustered in specific patient rooms but did occur frequently when the HVAC systems were not in use, prior to intervention (i.e., sealing and disuse of AHUs in private room), and during construction of a new hospital building. Multivariate logistic regression analysis of initial episodes of febrile neutropenia showed that the rate of febrile neutropenia was significantly associated with the duration of neutropenia (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.07-1.27) and with sex (OR: 0.469; CI: 0.239-0.902). An evaluation of private rooms showed that female patients also had a lower rate of fever after intervention (OR: 0.0016; 95% CI: 0.000-0.209). The reduced rate of febrile neutropenia after intervention suggests that mold colonization of AHUs had adverse effects on patients with hematological malignancies.

The neurobiology of the human febrile response.

PubMed

Biddle, Chuck

2006-04-01

Fever is a normal adaptation in response to a pyrogenic stimulus resulting in the generation of cytokines and prostaglandins. Fever differs from hyperpyrexia and hyperthermia associated with hot environs and pharmacological triggers. Typically, pyrogens are infectious organisms or their direct products (toxins). The body produces a wide array of pyrogenic cytokines such as interleukins (IL-1, IL-6), interferon, and tumor necrosis factor. Tissue trauma can trigger the febrile response, as can infectious organisms, certain medications, and blood products. The circumventricular organ system (CVOS) is neuronal tissues lying outside the blood-brain barrier that has a key role in initiating the communication sequence responsible for the synthesis of febrile prostaglandins. When pyrogenic cytokines are detected by the CVOS, prostaglandin synthesis, especially cyclooxygenase-dependent prostaglandin E2, is induced, activating the febrile response. Once the appropriate signal is received by the hypothalamus, autonomic, endocrine, and behavioral processes are activated until the hypothalamic set-point is reset downward as a consequence of a reduction in pyrogen content or antipyretic therapy, with subsequent heat loss. There is little evidence that fever facilitates recovery from disease or assists the immune system in mounting a response. Antipyretics are used commonly to decrease the distressing manifestations associated with fever.

Urinary tract infections in pediatric oncology patients with fever and neutropenia.

PubMed

Sandoval, Claudio; Sinaki, Banafsheh; Weiss, Robert; Munoz, Jose; Ozkaynak, M Fevzi; Tugal, Oya; Jayabose, Somasundaram

2012-02-01

The relevancy of the urinary tract as a source of infection during febrile neutropenia is not known. The authors sought to determine the frequency of urinary tract infections (UTIs) in pediatric cancer patients with febrile neutropenia. Urine was collected from a mid-stream void before the administration of antibiotics. Demographic, clinical, and laboratory data were collected. The frequency of UTI and usefulness of urinalysis and localizing signs in predicting UTI in pediatric cancer patients with fever and neutropenia were determined. Forty-five patients had 58 febrile neutropenic episodes eligible for study participation. No patient presented with localizing signs. The urinalysis was negative in 53 episodes and positive in 5 episodes. Four patients had 5 UTIs. The frequency of UTI was 8.6% (5 of 58 febrile neutropenia episodes). Four patients had bacteremia, none of whom had a UTI. The sensitivity, specificity, and negative predictive value of urinalysis was 40%, 94%, and 94%, respectively, and for localizing signs was undefined, 100%, and 91%, respectively. UTI is as common as bacteremia in the current pediatric cancer patients with fever and neutropenia. Urinalysis and urine culture should be obtained routinely as part of the diagnostic evaluation of patients with fever and neutropenia.

New Methods for the Detection and Interception of Frequency-Hopped Waveforms

DTIC Science & Technology

1990-11-01

that £[p2 Q2 /O] = uF + 2 + o(cos 0 + 6 sin9)2 + 4n(acos0+/3sin)(7ycos0+6sinO)+o r(acos0+sinO)2 I + ( acosO +/3sinO) 2(Tcos9+ 6sin O)2 (3.134) i which...Jcins I lopk ins lI mvtrsi! t3 A pplied Physics Laborator Before1 NII After Figure 4.4: Deconvolut ion Applivod to Oi-fFci i r 100 The Johns 11opkins...Arlington, VA 20360 Library 2 Naval Postgraduate School Monterey, CA 92940 Library 2 Naval Research Laborator . Washington, DC 20375 Library 2 J. W

Investigation on navigation patterns of inertial/celestial integrated systems

NASA Astrophysics Data System (ADS)

Luo, Dacheng; Liu, Yan; Liu, Zhiguo; Jiao, Wei; Wang, Qiuyan

2014-11-01

It is known that Strapdown Inertial Navigation System (SINS), Global Navigation Satellite System (GNSS) and Celestial Navigation System (CNS) can complement each other's advantages. The SINS/CNS integrated system, which has the characteristics of strong autonomy, high accuracy and good anti-jamming, is widely used in military and civilian applications. Similar to SINS/GNSS integrated system, the SINS/CNS integrated system can also be divided into three kinds according to the difference of integrating depth, i.e., loosely coupled pattern, tightly coupled pattern and deeply coupled pattern. In this paper, the principle and characteristics of each pattern of SINS/CNS system are analyzed. Based on the comparison of these patterns, a novel deeply coupled SINS/CNS integrated navigation scheme is proposed. The innovation of this scheme is that a new star pattern matching method aided by SINS information is put forward. Thus the complementary features of these two subsystems are reflected.

SAP30L interacts with members of the Sin3A corepressor complex and targets Sin3A to the nucleolus

PubMed Central

Viiri, K. M.; Korkeamäki, H.; Kukkonen, M. K.; Nieminen, L. K.; Lindfors, K.; Peterson, P.; Mäki, M.; Kainulainen, H.; Lohi, O.

2006-01-01

Histone acetylation plays a key role in the regulation of gene expression. The chromatin structure and accessibility of genes to transcription factors is regulated by enzymes that acetylate and deacetylate histones. The Sin3A corepressor complex recruits histone deacetylases and in many cases represses transcription. Here, we report that SAP30L, a close homolog of Sin3-associated protein 30 (SAP30), interacts with several components of the Sin3A corepressor complex. We show that it binds to the PAH3/HID (Paired Amphipathic Helix 3/Histone deacetylase Interacting Domain) region of mouse Sin3A with residues 120–140 in the C-terminal part of the protein. We provide evidence that SAP30L induces transcriptional repression, possibly via recruitment of Sin3A and histone deacetylases. Finally, we characterize a functional nucleolar localization signal in SAP30L and show that SAP30L and SAP30 are able to target Sin3A to the nucleolus. PMID:16820529

Chromatin associated Sin3A is essential for male germ cell lineage in the mouse

PubMed Central

Pellegrino, Jessica; Castrillon, Diego H.; David, Gregory

2012-01-01

Spermatogenesis is a complex process that requires coordinated proliferation and differentiation of male germ cells. The molecular events that dictate this process are largely unknown, but are likely to involve highly regulated transcriptional control. In this study, we investigate the contribution of chromatin associated Sin3A in mouse germ cell lineage development. Genetic inactivation of Sin3A in the male germline leads to sterility that results from the early and penetrant apoptotic death observed in Sin3A-deleted germ cells, coincident with the reentry in mitosis. Sin3A-deleted testes exhibit a Sertoli-cell only phenotype, consistent with the absolute requirement for Sin3A in germ cells’ development and/or viability. Interestingly, transcripts analysis revealed that the expression program of Sertoli cells is altered upon inactivation of Sin3A in germ cells. These studies identified a central role for the mammalian Sin3-HDAC complex in the germ cell lineage, and point to an exquisite transcriptional crosstalk between germ cells and their niche to support fertility in mammals. PMID:22820070

Itaya virus, a Novel Orthobunyavirus Associated with Human Febrile Illness, Peru.

PubMed

Hontz, Robert D; Guevara, Carolina; Halsey, Eric S; Silvas, Jesus; Santiago, Felix W; Widen, Steven G; Wood, Thomas G; Casanova, Wilma; Vasilakis, Nikos; Watts, Douglas M; Kochel, Tadeusz J; Ebihara, Hideki; Aguilar, Patricia V

2015-05-01

Our genetic analyses of uncharacterized bunyaviruses isolated in Peru identified a possible reassortant virus containing small and large gene segment sequences closely related to the Caraparu virus and a medium gene segment sequence potentially derived from an unidentified group C orthobunyavirus. Neutralization tests confirmed serologic distinction among the newly identified virus and the prototype and Caraparu strains. This virus, named Itaya, was isolated in 1999 and 2006 from febrile patients in the cities of Iquitos and Yurimaguas in Peru. The geographic distance between the 2 cases suggests that the Itaya virus could be widely distributed throughout the Amazon basin in northeastern Peru. Identification of a new Orthobunyavirus species that causes febrile disease in humans reinforces the need to expand viral disease surveillance in tropical regions of South America.

Itaya virus, a Novel Orthobunyavirus Associated with Human Febrile Illness, Peru

PubMed Central

Hontz, Robert D.; Guevara, Carolina; Halsey, Eric S.; Silvas, Jesus; Santiago, Felix W.; Widen, Steven G.; Wood, Thomas G.; Casanova, Wilma; Vasilakis, Nikos; Watts, Douglas M.; Kochel, Tadeusz J.; Ebihara, Hideki

2015-01-01

Our genetic analyses of uncharacterized bunyaviruses isolated in Peru identified a possible reassortant virus containing small and large gene segment sequences closely related to the Caraparu virus and a medium gene segment sequence potentially derived from an unidentified group C orthobunyavirus. Neutralization tests confirmed serologic distinction among the newly identified virus and the prototype and Caraparu strains. This virus, named Itaya, was isolated in 1999 and 2006 from febrile patients in the cities of Iquitos and Yurimaguas in Peru. The geographic distance between the 2 cases suggests that the Itaya virus could be widely distributed throughout the Amazon basin in northeastern Peru. Identification of a new Orthobunyavirus species that causes febrile disease in humans reinforces the need to expand viral disease surveillance in tropical regions of South America. PMID:25898901

Aminoglycosides Monotherapy as First-Line Treatment for Febrile Urinary Tract Infection in Children.

PubMed

Poey, Nora; Madhi, Fouad; Biscardi, Sandra; Béchet, Stéphane; Cohen, Robert

2017-11-01

We report a retrospective monocentric descriptive study performed in CHI Creteil for 20 months to describe the management and outcome of amikacin monotherapy as an alternative to third-generation cephalosporins for empiric treatment of febrile urinary tract infection (FUTI) in children. Data were analyzed for 151 children, and 90 selected cases were classified as certain or highly probable FUTI. Escherichia coli infection was found in 89 cases. In all patients, fever was resolved within 72 hours after beginning amikacin treatment. Only 5.3% of children were febrile after 48 hours. The mean amikacin treatment duration was 3.05 ± 0.13 days before oral treatment began (guided by antibiotic susceptibility testing). Amikacin monotherapy seems effective for the initial management of FUTI in children.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Qingqiao; Xia, Yuanyu, E-mail: xiayuanyu.wh@gmail.com; Wang, Guan

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression inmore » HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.« less

Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003

PubMed Central

Vega, Vinsensius B; Ruan, Yijun; Liu, Jianjun; Lee, Wah Heng; Wei, Chia Lin; Se-Thoe, Su Yun; Tang, Kin Fai; Zhang, Tao; Kolatkar, Prasanna R; Ooi, Eng Eong; Ling, Ai Ee; Stanton, Lawrence W; Long, Philip M; Liu, Edison T

2004-01-01

Background The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. Methods We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V), cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L), and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5) arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. Results Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14th October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 × 10-6 nucleotide substitutions per site per day (0.17 mutations per genome per day), or two mutations per human passage (adjusted R-square = 0.4014). Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are geographically associated: two Singapore isolates, one Taiwan isolate, and one North China isolate which appears most closely related to the putative SARS-CoV isolated from a palm civet. Non-synonymous mutations are centered in non-essential ORFs especially in structural and antigenic genes such as the S and M proteins, but these mutations did not distinguish the geographical groupings. However, no non-synonymous mutations were found in the 3CLpro and the polymerase genes. Conclusions Our results show that the SARS-CoV is well adapted to growth in culture and did not appear to undergo specific selection in human populations. We further assessed that the putative origin of the SARS epidemic was in late October 2002 which is consistent with a recent estimate using cases from China. The greater sequence divergence in the structural and antigenic proteins and consistent deletions in the 3' – most portion of the viral genome suggest that certain selection pressures are interacting with the functional nature of these validated and putative ORFs. PMID:15347429

Q Fever, Scrub Typhus, and Rickettsial Diseases in Children, Kenya, 2011-2012.

PubMed

Maina, Alice N; Farris, Christina M; Odhiambo, Antony; Jiang, Ju; Laktabai, Jeremiah; Armstrong, Janice; Holland, Thomas; Richards, Allen L; O'Meara, Wendy P

2016-05-01

To increase knowledge of undifferentiated fevers in Kenya, we tested paired serum samples from febrile children in western Kenya for antibodies against pathogens increasingly recognized to cause febrile illness in Africa. Of patients assessed, 8.9%, 22.4%, 1.1%, and 3.6% had enhanced seroreactivity to Coxiella burnetii, spotted fever group rickettsiae, typhus group rickettsiae, and scrub typhus group orientiae, respectively.

Domestically acquired fascioliasis in northern California.

PubMed

Weisenberg, Scott A; Perlada, David E

2013-09-01

Two cases of domestically acquired fascioliasis are reported. Patient One was a 63-year-old male who developed a febrile illness 2 months after eating watercress in Marin County. Patient Two was a 38-year-old male who had eaten watercress with Patient One, and also developed a febrile illness. Both patients had eosinophilia and liver lesions on imaging. Diagnosis was made by serology and treatment was with triclabendazole.

Prenatal Stress and Risk of Febrile Seizures in Children: A Nationwide Longitudinal Study in Denmark

ERIC Educational Resources Information Center

Li, Jiong; Olsen, Jorn; Obel, Carsten; Christensen, Jakob; Precht, Dorthe Hansen; Vestergaard, Mogens

2009-01-01

We aimed to examine whether exposure to prenatal stress following maternal bereavement is associated with an increased risk of febrile seizures. In a longitudinal population-based cohort study, we followed 1,431,175 children born in Denmark. A total of 34,777 children were born to women who lost a close relative during pregnancy or within 1 year…

The Characterization and Treatment of Aggressive Breast Cancer

DTIC Science & Technology

2007-05-01

of febrile neutropenia , G- CSF should be given with the next cycle. For an episode of febrile neutropenia despite dose reduction and G-CSF, protocol...permitted, and should be documented. 5.2.3 The use of granulocyte colony stimulating agents should only be used if there is persistent neutropenia ... neutropenia , leukopenia, more pronounced in patients with compromised renal function Gastrointestinal: nausea and vomiting, treatable with moderate doses

U.S. Army Medical Department Journal (April-June 2006)

DTIC Science & Technology

2006-06-01

sensitive groupings, gastrointestinal, respiratory, febrile , dermatological, psychological, and cause- stratified traumatic injuries. It should be...suffering from (an) obscure febrile disease” which “defied definite identification.”1 Invariably, each of these Soldiers had been training at nearby... neutropenia occurring on or about the second or third day of symptoms. The total white blood cell count frequently dropped to about 3,000/µl and

Prevalence of Lassa Virus Disease (LVD) in Nigerian children with fever or fever and convulsions in an endemic area

PubMed Central

Akhuemokhan, Odigie C.; Ewah-Odiase, Rosemary O.; Akpede, Nosa; Ehimuan, Jacqueline; Adomeh, Donatus I.; Odia, Ikpomwonsa; Olomu, Sylvia C.; Pahlmann, Meike; Becker-Ziaja, Beate; Happi, Christian T.; Asogun, Danny A.; Okogbenin, Sylvanus A.; Okokhere, Peter O.; Dawodu, Osagie S.; Omoike, Irekpono U.; Sabeti, Pardis C.; Günther, Stephan; Akpede, George O.

2017-01-01

Background Convulsions with fever in children are a common neurologic emergency in the tropics, and determining the contribution of endemic viral infections can be challenging. In particular, there is a dearth of data on the prevalence and clinical differentiation of Lassa virus disease (LVD) in febrile children in endemic areas of Nigeria, which has multiple lineages of the virus. The aim of this study was to determine the prevalence and presentation of LVD in febrile children with and without convulsions. Methodology/Principal findings This was a prospective study of consecutive febrile children aged ≥1 month– 15 years admitted to the Children’s Emergency Room of Irrua Specialist Teaching Hospital over a period of 1 year. Febrile children with convulsions (Cases) were compared with those without convulsions (Controls). LVD was defined by the presence of a positive Lassa virus RT-PCR test. Rates were compared between groups using χ2 or Fisher’s exact tests and p <0.05 taken as significant. 373 (40.9%) of 913 admissions had fever. Of these, 108/373 (29%) presented with convulsions. The overall prevalence of LVD was 13/373 (3.5%; 95% CI = 1.9%, 5.7%) in febrile admissions, 3/108 (2.8%) in Cases and 10/265 (3.8%) in Controls [(Odds Ratio (95% Confidence Interval) (OR (95% CI)) of LVD in Cases versus Controls = 0.73 (0.2, 2.7)]. Only vomiting (OR (95% CI) = 0.09 (0.01, 0.70)) and bleeding (OR (95% CI) = 39.56 (8.52, 183.7)) were significantly associated with an increased prevalence of LVD. Conclusions/Significance LVD is an important cause of fever, including undifferentiated fever in children in endemic areas, but it is not significantly associated with convulsions associated with fever. Its prevalence, and lack of clinical differentiation on presentation, underscores the importance of a high index of suspicion in diagnosis. Screening of febrile children with undifferentiated fever in endemic areas for LVD could be an important medical and public health control measure. PMID:28671959

Clinical outcomes in Mexican children with febrile acute upper respiratory tract infections: no impact of antibiotic therapy.

PubMed

Carranza-Martinez, Martha I; Newton-Sanchez, Oscar; Franco-Paredes, Carlos; Villaseñor-Sierra, Alberto

2010-09-01

To compare the clinical outcomes (duration of signs and symptoms) and the microbiology in Mexican children with non-complicated febrile upper respiratory tract infections (URI), with and without the use of antibiotics. We conducted a prospective cohort study from September 2006 to July 2007. The study population consisted of 880 children aged 6 months to 5 years 11 months, attending four community daycare centers run by the Instituto Mexicano del Seguro Social (IMSS) and three non-IMSS daycare centers. Children with a febrile URI were enrolled before receiving any antimicrobials and were followed up for two weeks. Duration of the fever, cough, runny nose, stuffy nose, irritability, loss of appetite, tiredness, and diarrhea, and isolation of Haemophilus influenzae,Streptococcus pneumoniae, and Streptococcus pyogenes were compared in those children who received antibiotic treatment and those who did not receive antibiotics. During the study period, a total of 145 out of 880 children were enrolled, and among those enrolled, 85/145 (59%) children received antibiotics. There was no significant difference in the duration of the signs and symptoms evaluated in the two groups. Although the proportions of S. pneumoniae, H. influenzae, and S. pyogenes isolated in children with and without antibiotics were comparable, those in whom we isolated S. pneumoniae had both a significantly longer episode of URI, as well as longer lasting diarrhea. Similarly, children receiving trimethoprim-sulfamethoxazole treatment experienced significantly longer durations of fever and diarrhea. The mean duration of signs and symptoms and the microbiological isolates of children with febrile URI were comparable among children treated with or without antibiotics, with the exception of a longer duration of URI and diarrhea in those children with an S. pneumoniae isolate. Our findings suggest that in our population, most cases of febrile URI are caused by viral infections, and demonstrate that antibiotics should not be used routinely in children with non-complicated febrile URI. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children

PubMed Central

Nyirenda, James T.; Tembo, Dumizulu L.; Storm, Janet; Dube, Queen; Msefula, Chisomo L.; Jambo, Kondwani C.; Mwandumba, Henry C.; Heyderman, Robert S.; Gordon, Melita A.

2017-01-01

ABSTRACT Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the humoral and cellular immunity of the host to NTS, which increases the susceptibility of the host to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi, and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole-blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S. Typhimurium were reduced in febrile P. falciparum-infected children (median, −0.20 log10 [interquartile range {IQR}, −1.85, 0.32]) compared to nonfebrile malaria-negative children (median, −1.42 log10 [IQR, −2.0, −0.47], P = 0.052). In relation to SBA, C3 deposition on S. Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 7.5% [IQR, 4.1, 15.0]) compared to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P = 0.048). WBBA with respect to S. Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 0.25 log10 [IQR, −0.73, 1.13], P = 0.0001) compared to nonfebrile malaria-negative children (median, −1.0 log10 [IQR, −1.68, −0.16]). In relation to WBBA, S. Typhimurium-specific NRBA was reduced in febrile P. falciparum-infected children (median, 8.8% [IQR, 3.7, 20], P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR, 33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S. Typhimurium in children during malaria episodes, which may explain the increased risk of iNTS observed in children from settings of malaria endemicity. The mechanisms underlying humoral immunity impairment are incompletely understood and should be explored further. PMID:28515136

Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children.

PubMed

Nyirenda, Tonney S; Nyirenda, James T; Tembo, Dumizulu L; Storm, Janet; Dube, Queen; Msefula, Chisomo L; Jambo, Kondwani C; Mwandumba, Henry C; Heyderman, Robert S; Gordon, Melita A; Mandala, Wilson L

2017-07-01

Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the humoral and cellular immunity of the host to NTS, which increases the susceptibility of the host to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi, and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole-blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S Typhimurium were reduced in febrile P. falciparum -infected children (median, -0.20 log10 [interquartile range {IQR}, -1.85, 0.32]) compared to nonfebrile malaria-negative children (median, -1.42 log10 [IQR, -2.0, -0.47], P = 0.052). In relation to SBA, C3 deposition on S Typhimurium was significantly reduced in febrile P. falciparum -infected children (median, 7.5% [IQR, 4.1, 15.0]) compared to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P = 0.048). WBBA with respect to S Typhimurium was significantly reduced in febrile P. falciparum -infected children (median, 0.25 log10 [IQR, -0.73, 1.13], P = 0.0001) compared to nonfebrile malaria-negative children (median, -1.0 log10 [IQR, -1.68, -0.16]). In relation to WBBA, S Typhimurium-specific NRBA was reduced in febrile P. falciparum -infected children (median, 8.8% [IQR, 3.7, 20], P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR, 33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S Typhimurium in children during malaria episodes, which may explain the increased risk of iNTS observed in children from settings of malaria endemicity. The mechanisms underlying humoral immunity impairment are incompletely understood and should be explored further. Copyright © 2017 Nyirenda et al.

Management of febrile children under five years in hospitals and health centres of rural Ghana.

PubMed

Webster, Jayne; Baiden, Frank; Bawah, Justina; Bruce, Jane; Tivura, Mathilda; Delmini, Rupert; Amenga-Etego, Seeba; Chandramohan, Daniel; Owusu-Agyei, Seth

2014-07-09

The case management of febrile children in hospitals' and health centres' pre-roll out of the new WHO policy on parasitological diagnosis was assessed. The delivery of artemisinin combination therapy (ACT) at these two levels of the health system was compared. Structured observations and exit interviews of 1,222 febrile children attending five hospitals and 861 attending ten health centres were conducted in six districts of the Brong Ahafo Region of Ghana. Effectiveness of delivery of case management of malaria was assessed. Proportions of children receiving ACT, anti-malarial monotherapy and antibiotics were described. Predictors of: a febrile child being given an ACT, a febrile child being given an antibiotic and of carers knowing how to correctly administer the ACT were assessed using logistic regression models stratified by hospitals and health centres. The system's effectiveness of delivering an ACT to febrile children diagnosed with malaria (parasitologically or clinically) was 31.4 and 42.4% in hospitals and health centres, respectively. The most ineffective process was that of ensuring that carers knew how to correctly administer the ACT. Overall 278 children who were not given an ACT were treated with anti-malarial monotherapy other than quinine. The majority of these children, 232/278 were given amodiaquine, 139 of these were children attending hospitals and 93 attending health centres. The cadre of health staff conducting consultation was a common predictor of the outcomes of interest. Presenting symptoms and examinations conducted were predictive of being given an ACT in hospitals and antibiotic in hospitals and health centres but not of being given an ACT in health centres. Treatment-seeking factors were predictive of being given an ACT if it was more than seven days since the fever began and an antibiotic in hospitals but not in health centres. Interventions to improve adherence to negative parasitological tests are needed, together with guidance on dispensing of antibiotics, but improving the education of carers on how to administer ACT will lead to the greatest immediate increase in the effectiveness of case management. Guidance is needed on implementation of the new test-based treatment for malaria policy in health facilities.

[Periodic fever, aphthous stomatitis, pharyngitis and adenitis: PFAPA syndrome in Argentina].

PubMed

Rocco, R

2011-03-01

PFAPA syndrome is a benign, non-hereditary condition, of unknown etiology and pathogenesis. There are few reports of it in South America. The purpose of this article is to communicate the experience in a large pediatric hospital in Argentina. A total of 18 patients were diagnosed with PFAPA between 2002 and 2009 at the Medium Risk Clinic, Prof. Dr. Juan P. Garrahan Pediatrics Hospital, Buenos Aires City. The modified criteria reported by Thomas et al were used for diagnosis. The follow up continued with evaluations during new febrile episodes, clinic check ups and telephone calls. The mean age at onset of symptoms was 2.5 years (range: 0.4-7.5) and the mean lag time from onset of symptoms and diagnosis was 3.2 years (range: 0.4-10.9). Fever episodes lasted for a mean of 4.5 days (range: 2-8), with a mean interval of 23 days (range: 15-30) between the beginning of the attacks. Febrile episodes were treated with methyl prednisone at a dose of 1mg/kg or betamethasone at a dose of 0.15mg/kg in a single dose. With a mean follow up of 2.6 years (range: 0.5-5.9) 13 patients remain with febrile episodes at a mean interval of 4.6 months (range: 1-12). Five patients did not have febrile crisis for more than a year during the study period and they are considered cured; in this group the disease lasted a mean of 4.7 years (1-9.7). PFAPA syndrome is a sporadic, difficult to diagnose, condition. Both methyl-prednisone and betamethasone have shown to be effective in controlling the symptoms during the febrile crisis. The definitive remission of the syndrome may occur in the first years of onset, although in most patients the febrile episodes continue with an increase of free intervals and attenuated symptoms, and full recovery in prepuberty or adolescence with no sequelae. Copyright © 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Two-year evaluation of Intermittent Preventive Treatment for Children (IPTc) combined with timely home treatment for malaria control in Ghana.

PubMed

Ahorlu, Collins K; Koram, Kwadwo A; Seake-Kwawu, Atsu; Weiss, Mitchell G

2011-05-15

Intermittent preventive treatment (IPT) has recently been accepted as an important component of the malaria control strategy. Intermittent preventive treatment for children (IPTc) combined with timely treatment of malaria related febrile illness at home to reduce parasite prevalence and malaria morbidity in children aged between six and 60 months in a coastal community in Ghana. This paper reports persistence of reduced parasitaemia two years into the intervention. The baseline and year-one-evaluation findings were published earlier. The main objective in the second year was to demonstrate whether the two interventions would further reduce parasite prevalence and malaria-related febrile illness in the study population. This was an intervention study designed to compare baseline and evaluation findings without a control group. The study combined home-based delivery of intermittent preventive treatment for children (IPTc) aged 6 - 60 months and home treatment of suspected febrile malaria-related illness within 24 hours. All children aged 6-60 months received home-based delivery of intermittent preventive treatment using amodiaquine + artesunate, delivered at home by community assistants every four months (6 times in 24 months). Malaria parasite prevalence surveys were conducted before the first and after the third and sixth IPTc to the children. The evaluation surveys were done four months after the third and sixth IPTc was given. Parasite prevalence which reduced from 25% to 3.0% at year-one evaluation had reduced further from 3% to 1% at year-two-evaluation. At baseline, 13.8% of the children were febrile (axilary temperature of ≥ 37.5 °C) compared to 2.2% at year-one-evaluation while 2.1% were febrile at year-two-evaluation. The year-two-evaluation result indicates that IPTc given three times in a year (every four months) combined with timely treatment of febrile malaria illness, is effective to reduce malaria parasite prevalence in children aged 6 to 60 months in the study community. This must give hope to malaria control programme managers in sub-Saharan Africa where the burden of the disease is most debilitating.

Could Neutrophil CD64 Expression Be Used as a Diagnostic Parameter of Bacteremia in Patients with Febrile Neutropenia?

PubMed

Efe İris, Nur; Yıldırmak, Taner; Gedik, Habip; Şimşek, Funda; Aydın, Demet; Demirel, Naciye; Yokuş, Osman

2017-06-05

The aim of this study is to investigate if neutrophil CD64 expression in febrile neutropenia patients could be used as an early indicator of bacteremia. All consecutive patients older than 18 years of age who had developed febrile neutropenia episodes due to hematological malignancies were included in the study. Those patients who had significant growth in their blood cultures constituted the case group, while those who had febrile neutropenia without any growth in their cultures and who did not have any documented infections formed the control group. Blood culture bottles were incubated in the Bact ALERT 3D system (bioMerieux, France), identification and susceptibility testing were performed using an automated broth microdilution method (VITEK 2, bioMerieux), and CD64 expression analysis was performed by the flow cytometry method. C-reactive protein (CRP) was measured by turbidimetric methods (Biosystems, Spain) and erythrocyte sedimentation rate (ESR) was measured by the Wintrobe method. In total, we prospectively evaluated 31 febrile episodes. The case group consisted of 17 patients while the control group included 14 patients. CD64 was found on neutrophils of the case group patients with a mean count of 8006 molecules/cell and of control group with a mean count of 2786 molecules/cell. CD64 levels of the case group were significantly higher than those of the control group (p=0.005). In the differentiation of the case group from the control group, a 2500 cut-off value for CD64 had significant [AUC=0.792 (0.619-0.965)] predictive value (p=0.001). In the prediction of patients with a 2500 cut-off value for CD64, sensitivity was 94.1%, positive predictive value was 76.2%, specificity was 64.3%, and negative predictive value was 90.0%. CRP levels and ESR values did not differ significantly between the groups (p=0.005). Neutrophil CD64 expression could be a good predictor as an immune parameter with high sensitivity and a negative predictive value for bacteremia in febrile neutropenic patients.

Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production.

PubMed

Kolly, Laeticia; Busso, Nathalie; von Scheven-Gete, Annette; Bagnoud, Nathaliane; Moix, Isabelle; Holzinger, Dirk; Simon, Gregoire; Ives, Annette; Guarda, Greta; So, Alexander; Morris, Michael A; Hofer, Michaël

2013-06-01

The exact pathogenesis of the pediatric disorder periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome is unknown. We hypothesized that PFAPA might be due to dysregulated monocyte IL-1β production linked to genetic variants in proinflammatory genes. Fifteen patients with PFAPA syndrome were studied during and outside a febrile episode. Hematologic profile, inflammatory markers, and cytokine levels were measured in the blood. The capacity of LPS-stimulated PBMCs and monocytes to secrete IL-1β was assessed by using ELISA, and active IL-1β secretion was visualized by means of Western blotting. Real-time quantitative PCR was performed to assess cytokine gene expression. DNA was screened for variants of the MEFV, TNFRSF1A, MVK, and NLRP3 genes in a total of 57 patients with PFAPA syndrome. During a febrile attack, patients with PFAPA syndrome revealed significantly increased neutrophil counts, erythrocyte sedimentation rates, and C-reactive protein, serum amyloid A, myeloid-related protein 8/14, and S100A12 levels compared with those seen outside attacks. Stimulated PBMCs secreted significantly more IL-1β during an attack (during a febrile episode, 575 ± 88 pg/mL; outside a febrile episode, 235 ± 56 pg/mL; P < .001), and this was in the mature active p17 form. IL-1β secretion was inhibited by ZYVAD, a caspase inhibitor. Similar results were found for stimulated monocytes (during a febrile episode, 743 ± 183 pg/mL; outside a febrile episode, 227 ± 92 pg/mL; P < .05). Genotyping identified variants in 15 of 57 patients, with 12 NLRP3 variants, 1 TNFRSF1A variant, 4 MEFV variants, and 1 MVK variant. Our data strongly suggest that IL-1β monocyte production is dysregulated in patients with PFAPA syndrome. Approximately 20% of them were found to have NLRP3 variants, suggesting that inflammasome-related genes might be involved in this autoinflammatory syndrome. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Arboviral Etiologies of Acute Febrile Illnesses in Western South America, 2000–2007

PubMed Central

Forshey, Brett M.; Guevara, Carolina; Laguna-Torres, V. Alberto; Cespedes, Manuel; Vargas, Jorge; Gianella, Alberto; Vallejo, Efrain; Madrid, César; Aguayo, Nicolas; Gotuzzo, Eduardo; Suarez, Victor; Morales, Ana Maria; Beingolea, Luis; Reyes, Nora; Perez, Juan; Negrete, Monica; Rocha, Claudio; Morrison, Amy C.; Russell, Kevin L.; J. Blair, Patrick; Olson, James G.; Kochel, Tadeusz J.

2010-01-01

Background Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public health relevance, little is know about the geographic distribution, relative impact, and risk factors for arbovirus infection in many regions of the world. Our objectives were to describe the arboviruses associated with acute undifferentiated febrile illness in participating clinics in four countries in South America and to provide detailed epidemiological analysis of arbovirus infection in Iquitos, Peru, where more extensive monitoring was conducted. Methodology/Findings A clinic-based syndromic surveillance system was implemented in 13 locations in Ecuador, Peru, Bolivia, and Paraguay. Serum samples and demographic information were collected from febrile participants reporting to local health clinics or hospitals. Acute-phase sera were tested for viral infection by immunofluorescence assay or RT-PCR, while acute- and convalescent-phase sera were tested for pathogen-specific IgM by ELISA. Between May 2000 and December 2007, 20,880 participants were included in the study, with evidence for recent arbovirus infection detected for 6,793 (32.5%). Dengue viruses (Flavivirus) were the most common arbovirus infections, totaling 26.0% of febrile episodes, with DENV-3 as the most common serotype. Alphavirus (Venezuelan equine encephalitis virus [VEEV] and Mayaro virus [MAYV]) and Orthobunyavirus (Oropouche virus [OROV], Group C viruses, and Guaroa virus) infections were both observed in approximately 3% of febrile episodes. In Iquitos, risk factors for VEEV and MAYV infection included being male and reporting to a rural (vs urban) clinic. In contrast, OROV infection was similar between sexes and type of clinic. Conclusions/Significance Our data provide a better understanding of the geographic range of arboviruses in South America and highlight the diversity of pathogens in circulation. These arboviruses are currently significant causes of human illness in endemic regions but also have potential for further expansion. Our data provide a basis for analyzing changes in their ecology and epidemiology. PMID:20706628

Expression of the SIN3 homologue from banana, MaSIN3, suppresses ABA responses globally during plant growth in Arabidopsis.

PubMed

Luxmi, Raj; Garg, Rashmi; Srivastava, Sudhakar; Sane, Aniruddha P

2017-11-01

The SIN3 family of co-repressors is a family of highly conserved eukaryotic repressor proteins that regulates diverse functions in yeasts and animals but remains largely uncharacterized functionally even in plants like Arabidopsis. The sole SIN3 homologue in banana, MaSIN3, was identified as a 1408 amino acids, nuclear localized protein conserved to other SIN3s in the PAH, HID and HCR domains. Interestingly, MaSIN3 over-expression in Arabidopsis mimics a state of reduced ABA responses throughout plant development affecting growth processes such as germination, root growth, stomatal closure and water loss, flowering and senescence. The reduction in ABA responses is not due to reduced ABA levels but due to suppression of expression of several transcription factors mediating ABA responses. Transcript levels of negative regulators of germination (ABI3, ABI5, PIL5, RGL2 and RGL3) are reduced post-imbibition while those responsible for GA biosynthesis are up-regulated in transgenic MaSIN3 over-expressers. ABA-associated transcription factors are also down-regulated in response to ABA treatment. The HDAC inhibitors, SAHA and sodium butyrate, in combination with ABA differentially suppress germination in control and transgenic lines suggesting the recruitment by MaSIN3 of HDACs involved in suppression of ABA responses in different processes. The studies provide an insight into the ability of MaSIN3 to specifically affect a subset of developmental processes governed largely by ABA. Copyright © 2017 Elsevier B.V. All rights reserved.

Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

PubMed

Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

2016-09-02

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Bistability and Biofilm Formation in Bacillus subtilis

PubMed Central

Chai, Yunrong; Chu, Frances; Kolter, Roberto; Losick, Richard

2008-01-01

Summary Biofilms of Bacillus subtilis consist of long chains of cells that are held together in bundles by an extracellular matrix of exopolysaccharide and the protein TasA. The exopolysaccharide is produced by enzymes encoded by the epsA-O operon and the gene encoding TasA is located in the yqxM-sipW-tasA operon. Both operons are under the control of the repressor SinR. Derepression is mediated by the antirepressor SinI, which binds to SinR with a 1:1 stoichiometry. Paradoxically, in medium promoting derepression of the matrix operons, the overall concentration of SinR in the culture greatly exceeded that of SinI. We show that under biofilm-promoting conditions sinI, which is under the control of the response regulator Spo0A, was expressed only in a small subpopulation of cells, whereas sinR was expressed in almost all cells. Activation of Spo0A is known to be subject to a bistable switch, and we infer that SinI reaches levels sufficient to trigger matrix production only in the subpopulation of cells in which Spo0A is active. Additionally, evidence suggests that sinI is expressed at intermediate, but not low or high, levels of Spo0A activity, which may explain why certain nutritional conditions are more effective in promoting biofilm formation than others. PMID:18047568

Comparison of urinary tract infection rates among 2- to 12-month-old febrile infants with RSV infections using 1999 and 2011 AAP diagnostic criteria.

PubMed

Kaluarachchi, Dinushan; Kaldas, Virginia; Roques, Euripedes; Nunez, Randolph; Mendez, Magda

2014-07-01

Infants with RSV infections have been found to have a clinically significant rate of urinary tract infections (UTIs). The American Academy of Pediatrics (AAP) published a revised Clinical Practice Guideline on UTIs in 2011, which includes major changes in diagnostic criteria for UTIs. Past research has been done using previous diagnostic criteria. The objective of the study is to assess the rate of UTIs in febrile infants with respiratory syncytial virus (RSV) infections according to the 2011 revised AAP Diagnostic Criteria and compare the rate of UTIs against the 1999 AAP Diagnostic Criteria. A retrospective comparative study of febrile infants (2-12 months) with RSV infections admitted to the Inpatient Pediatric unit of Lincoln Medical and Mental Center, Bronx, NY, from September through April 2006 to 2012. We applied the AAP's 1999 and 2011 diagnostic criteria for UTIs separately to assess the rates of UTIs. A total of 359 RSV-positive febrile patients who were investigated for UTIs were enrolled. Pyuria was found in 11.1% (40/359), positive urine culture 10 000 to 50 000 was found in 1.4% (5/359) and ≥50 000 in 4.7% (17/359). The rate of UTIs using AAP's 1999 criteria was 6.1% (22/359), and using the 2011 criteria the rate was 1.1% (4/359). The rate of UTIs was significantly different between the 2 groups (odds ratio [confidence interval] = 0.17 [0.05, 0.5], P = .001). The rate of UTIs in RSV-positive febrile infants is very low (1.1%) with the 2011 AAP diagnostic criteria. Previously described increased risk of UTIs may represent asymptomatic bacteriuria or contaminated specimens. © The Author(s) 2014.

TLR-4 polymorphisms and leukocyte TLR-4 expression in febrile UTI and renal scarring.

PubMed

Bayram, Meral Torun; Soylu, Alper; Ateş, Halil; Kızıldağ, Sefa; Kavukçu, Salih

2013-09-01

In this study, we aimed to determine the relation of TLR-4 Asp299Gly and Thr399Ile polymorphisms and monocyte/neutrophil TLR-4 expression to febrile urinary tract infection (UTI) and renal scar development in children. The study was performed in children with a history of febrile UTI. Patients with and without renal scarring were classified as group 1 and group 2, respectively, while the control cases in our previous study were used as the control group (group 3). All three groups were compared for the rate of TLR-4 Asp299Gly and Thr399Ile polymorphisms, and for basal and lipopolysaccharide-stimulated monocyte/neutrophil TLR-4 expression levels. There were 168 patients (86 in group 1, 82 in group 2) and 120 control cases. Monocyte/neutrophil TLR-4 expression levels were similar in groups 1 and 2. However, both groups had lower TLR-4 expression than group 3. The rate of TLR-4 Asp299Gly polymorphism was not different in all groups. TLR-4 Thr399Ile polymorphism was higher in groups 1 and 2 than in group 3 (14.0, 12.2, and 2.0 %, respectively), while group 1 and group 2 were not different. Furthermore, monocyte TLR-4 expression level was lower in those having TLR-4 Thr399Ile polymorphism than in those without this polymorphism. Patients with febrile UTI had more frequent TLR-4 Thr399Ile polymorphism and lower monocyte/neutrophil TLR-4 expression. These findings indicate that children carrying TLR-4 Thr399Ile polymorphism and/or having low level of monocyte/neutrophil TLR-4 expression have a tendency to develop febrile UTI. However, we could not show the association of TLR-4 polymorphisms and of TLR-4 expression level to renal scarring.

Utility of screening ultrasound after first febrile UTI among patients with clinically significant vesicoureteral reflux.

PubMed

Massanyi, Eric Z; Preece, Janae; Gupta, Angela; Lin, Susan M; Wang, Ming-Hsien

2013-10-01

To assess the sensitivity and negative predictive value (NPV) of screening renal and bladder ultrasound (RBUS) after initial febrile urinary tract infection (UTI) among patients with clinically significant vesicoureteral reflux (VUR). A retrospective review was performed of all children <2 years of age who presented with a febrile UTI between 2004 and 2011. The sensitivity and NPV of initial RBUS was calculated among patients who were found to have high-grade (IV-V) VUR. Additionally, initial RBUS among patients with evidence of photopenia on dimercaptosuccinic acid (DMSA) scan or who underwent surgical intervention were reviewed. One hundred forty-four patients with febrile UTI were identified; available RBUS, voiding cystourethrogram (VCUG), and DMSA results for each kidney were reviewed. One hundred fifty-eight kidneys had evidence of VUR on VCUG, and initial RBUS demonstrated abnormality in 25 (sensitivity 0.17). Forty-five kidneys had high-grade VUR and RBUS revealed abnormality in 16 (sensitivity 0.36). One hundred seventy-eight kidneys had no evidence of abnormality on initial RBUS, and 136 (76%) were found to have VUR (NPV 0.24), of which 31 had high-grade VUR (NPV 0.83). Seven kidneys had scarring on DMSA and initial RBUS was normal in 4 (57%). Twelve of 19 patients (63%) who eventually underwent surgical intervention had a normal initial RBUS. RBUS has poor sensitivity and NPV for detecting high-grade VUR in patients <2 years who present with a febrile UTI. A significant number of patients who were diagnosed with high-grade VUR, renal scarring, or underwent surgical correction of VUR had a negative screening RBUS. Copyright © 2013 Elsevier Inc. All rights reserved.

Early hospital discharge versus continued hospitalization in febrile pediatric cancer patients with prolonged neutropenia: A randomized, prospective study.

PubMed

Ahmed, Nabil; El-Mahallawy, Hadir A; Ahmed, Ibrahim A; Nassif, Shimaa; El-Beshlawy, Aamal; El-Haddad, Alaa

2007-11-01

Hospitalization with single or multi-agent antibiotic therapy has been the standard of care for treatment of febrile neutropenia in cancer patients. We hypothesized that an empiric antibiotic regimen that is effective and that can be administered once-daily will allow for improved hospital utilization by early transition to outpatient care. Febrile pediatric cancer patients with anticipated prolonged neutropenia were randomized between a regimen of once-daily ceftriaxone plus amikacin (C + A) and imipenem monotherapy (control). Afebrile patients on C + A satisfying "Early Discharge Criteria" at 72 hr continued treatment as outpatients. We compared the outcome, adverse events, duration of hospitalization, and cost between both groups. A prospective randomized controlled clinical trial was conducted on 129 febrile episodes in pediatric cancer patients with prolonged neutropenia. No adverse events were seen in 32 children (84% of study arm) treated on an outpatient basis. We found a statistically significant difference between the duration of hospitalization of the C + A group [median 5 days] and control [median 9 days](P < 0.001), per episode antibiotic cost (P < 0.001) and total episode cost (P < 0.001). There was no statistically significant difference in the response to treatment at 72 hr or after necessary antimicrobial modifications. We conclude that pediatric febrile cancer patients initially considered at risk for sepsis due to prolonged neutropenia can be re-evaluated at 72 hr for outpatient therapy. The convenience, low incidence of adverse effects, and cost benefit of the once-daily regimen of C + A may be particularly useful to reduce the overall treatment costs and duration of hospitalization. (c) 2007 Wiley-Liss, Inc.

Consensus Guidelines on Evaluation and Management of the Febrile Child Presenting to the Emergency Department in India.

PubMed

Mahajan, Prashant; Batra, Prerna; Thakur, Neha; Patel, Reena; Rai, Narendra; Trivedi, Nitin; Fassl, Bernhard; Shah, Binita; Lozon, Marie; Oteng, Rockerfeller A; Saha, Abhijeet; Shah, Dheeraj; Galwankar, Sagar

2017-08-15

India, home to almost 1.5 billion people, is in need of a country-specific, evidence-based, consensus approach for the emergency department (ED) evaluation and management of the febrile child. We held two consensus meetings, performed an exhaustive literature review, and held ongoing web-based discussions to arrive at a formal consensus on the proposed evaluation and management algorithm. The first meeting was held in Delhi in October 2015, under the auspices of Pediatric Emergency Medicine (PEM) Section of Academic College of Emergency Experts in India (ACEE-INDIA); and the second meeting was conducted at Pune during Emergency Medical Pediatrics and Recent Trends (EMPART 2016) in March 2016. The second meeting was followed with futher e-mail-based discussions to arrive at a formal consensus on the proposed algorithm. To develop an algorithmic approach for the evaluation and management of the febrile child that can be easily applied in the context of emergency care and modified based on local epidemiology and practice standards. We created an algorithm that can assist the clinician in the evaluation and management of the febrile child presenting to the ED, contextualized to health care in India. This guideline includes the following key components: triage and the timely assessment; evaluation; and patient disposition from the ED. We urge the development and creation of a robust data repository of minimal standard data elements. This would provide a systematic measurement of the care processes and patient outcomes, and a better understanding of various etiologies of febrile illnesses in India; both of which can be used to further modify the proposed approach and algorithm.

High prevalence and antimicrobial resistance of urinary tract infection isolates in febrile young children without localizing signs in Taiwan.

PubMed

Wu, Chang-Teng; Lee, Hao-Yuan; Chen, Chyi-Liang; Tuan, Pao-Lan; Chiu, Cheng-Hsun

2016-04-01

Antimicrobial susceptibility and prevalence of pediatric urinary tract infection (UTI) is very useful for pediatricians in selecting effective antibiotics in time to improve outcomes in patients. This study aimed to determine the prevalence rate, bacterial distribution, and antimicrobial susceptibility of UTI in febrile young children at a teaching hospital in northern Taiwan. From January 2011 to December 2011, all urinary isolates from suspected cases of UTI in febrile young children aged from 1 day to 36 months visiting the Pediatric Emergency Room of Chang Gung Children's Hospital, Taoyuan, Taiwan were identified by conventional methods. Antibiotic susceptibility was determined according to the Clinical and Laboratory Standards Institute. A total of 5470 (78%) from 7009 eligible children were enrolled in the study, and 619 (11.3%) had a diagnosis of UTI. The most prevalent bacterium was Escherichia coli (68%) followed by Klebsiella pneumoniae (8.1%) and Proteus mirabilis (6.8%). Ampicillin, piperacillin, and trimethoprim-sulfamethoxazole (TMP-SMX) showed a higher resistance rate in the three predominant bacteria. All tested bacteria showed higher resistance to ampicillin (79.3%) and TMP-SMX (44.1%), and lower resistance to cefazolin (17.7%) and gentamicin (13.0%). Fourteen percent of the isolates produced extended spectrum β-lactamase (ESBL), among which 93.33% were E. coli isolates. The overall prevalence of UTI in this study was higher than previously reported in febrile children. Higher antimicrobial resistance was found in ampicillin and TMP-SMX. Among commonly used antibiotics, cefazolin and gentamicin are recommended to treat UTI in febrile children aged < 3 years without localizing signs. Copyright © 2015. Published by Elsevier B.V.

Elevated postvoid residual urine volume predicting recurrence of urinary tract infections in toilet-trained children.

PubMed

Chang, Shang-Jen; Tsai, Li-Ping; Hsu, Chun-Kai; Yang, Stephen S

2015-07-01

The aim of this study was to examine whether toilet-trained children with a history of febrile urinary tract infection (fUTI) and elevated postvoid residual (PVR) urine volume according to a recently published PVR nomogram were at greater risk of UTI recurrence. One month after recovery from febrile UTI, constipation was diagnosed according to the Rome III criteria, and lower urinary tract (LUT) function was evaluated with two sets of uroflowmetry and PVR by ultrasonography. For children aged ≦ 6 and ≧ 7 years, elevated PVR is defined as >20 and >10 ml, respectively. Cox proportion hazards regression was used to evaluate the risk factors for recurrence of UTI. Between 2005 and 2011, 60 children aged 6.5 ± 2.5 years (boy:girl ratio 27:33) were enrolled for analysis. Univariate analysis showed that recurrent febrile UTI was more commonly observed in children with elevated PVR [repetitive elevated PVR: hazard ratio (HR) 5.75, 95% confidence interval (CI) 1.41-23.4; one elevated PVR: HR 4.53, 95% CI 1.01-20.2] and high-grade vesicoureteral reflux (VUR; HR 4.53, 95% CI 1.46-14.07). Multivariate analysis showed that younger age (HR 1.37, 95% CI 1.03-1.82, p < 0.01) and elevated PVR (HR 2.88, 95% CI 1.44-5.73, p = 0.01) were significant, independent risk factors for recurrent febrile UTI--but not gender, presence of high-grade VUR and constipation. Elevated PVR defined by the new PVR nomogram predicted recurrent UTI in children with history of febrile UTI. Care should be taken to manage children with elevated PVR.

Association of ABCB1 and SLC22A16 Gene Polymorphisms with Incidence of Doxorubicin-Induced Febrile Neutropenia: A Survey of Iranian Breast Cancer Patients.

PubMed

Faraji, Abolfazl; Dehghan Manshadi, Hamid Reza; Mobaraki, Maryam; Zare, Mahkameh; Houshmand, Massoud

2016-01-01

Breast cancer is the most common cancer in women worldwide. Doxorubicin-based chemotherapy is used to treat breast cancer patients; however, neutropenia is a common hematologic side effect and can be life-threatening. The ABCB1 and SLC22A16 genes encode proteins that are essential for doxorubicin transport. In this study, we explored the effect of 2 common polymorphisms in ABCB1 (rs10276036 C/T) and SLC22A16 (rs12210538 A/G) on the development of grade 3/4 febrile neutropenia in Iranian breast cancer patients. Our results showed no significant association between these polymorphisms and grade 3/4 febrile neutropenia; however, allele C of ABCB1 (rs10276036 C/T) (p = 0.315, OR = 1.500, 95% CI = 0.679-3.312) and allele A of SLC22A16 (rs12210538 A/G) (p = 0.110, OR = 2.984, 95% CI = 0.743-11.988) tended to have a greater association with grade 3/4 febrile neutropenia, whereas allele T of ABCB1 (rs10276036) (p = 0.130, OR = 0.515, 95% CI = 0.217-1.223) and allele G of SLC22A16 (rs12210538) (p = 0.548, OR = 0.786, 95% CI = 0.358-1.726) tended to protect against this condition. In addition to breast cancer, a statistically significant association was also observed between the development of grade 3/4 febrile neutropenia and other clinical manifestations such as stage IIIC cancer (p = 0.037) and other diseases (p = 0.026). Our results indicate that evaluation of the risk of grade 3/4 neutropenia development and consideration of molecular and clinical findings may be of value when screening for high-risk breast cancer patients.

Increased Nasopharyngeal Density and Concurrent Carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Are Associated with Pneumonia in Febrile Children.

PubMed

Chochua, Sopio; D'Acremont, Valérie; Hanke, Christiane; Alfa, David; Shak, Joshua; Kilowoko, Mary; Kyungu, Esther; Kaiser, Laurent; Genton, Blaise; Klugman, Keith P; Vidal, Jorge E

2016-01-01

We assessed nasopharyngeal (NP) carriage of five pathogens in febrile children with and without acute respiratory infection (ARI) of the upper (URTI) or lower tract, attending health facilities in Tanzania. NP swabs collected from children (N = 960) aged 2 months to 10 years, and with a temperature ≥38°C, were utilized to quantify bacterial density of S. pneumoniae (Sp), H. influenzae (Hi), M. catarrhalis (Mc), S. aureus (Sa), and N. meningitidis (Nm). We determined associations between presence of individual species, densities, or concurrent carriage of all species combination with respiratory diseases including clinical pneumonia, pneumonia with normal chest radiography (CXR) and endpoint pneumonia. Individual carriage, and NP density, of Sp, Hi, or Mc, but not Sa, or Nm, was significantly associated with febrile ARI and clinical pneumonia when compared to febrile non-ARI episodes. Density was also significantly increased in severe pneumonia when compared to mild URTI (Sp, p<0.002; Hi p<0.001; Mc, p = 0.014). Accordingly, concurrent carriage of Sp+, Hi+, and Mc+, in the absence of Sa- and Nm-, was significantly more prevalent in children with ARI (p = 0.03), or clinical pneumonia (p<0.001) than non-ARI, and in children with clinical pneumonia (p = 0.0007) than URTI. Furthermore, Sp+, Hi+, and Mc+ differentiated children with pneumonia with normal CXR, or endpoint pneumonia, from those with URTI, and non-ARI cases. Concurrent NP carriage of Sp, Hi, and Mc was a predictor of clinical pneumonia and identified children with pneumonia with normal CXR and endpoint pneumonia from those with febrile URTI, or non-ARI episodes.

Increased Nasopharyngeal Density and Concurrent Carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Are Associated with Pneumonia in Febrile Children

PubMed Central

2016-01-01

Background We assessed nasopharyngeal (NP) carriage of five pathogens in febrile children with and without acute respiratory infection (ARI) of the upper (URTI) or lower tract, attending health facilities in Tanzania. Methods NP swabs collected from children (N = 960) aged 2 months to 10 years, and with a temperature ≥38°C, were utilized to quantify bacterial density of S. pneumoniae (Sp), H. influenzae (Hi), M. catarrhalis (Mc), S. aureus (Sa), and N. meningitidis (Nm). We determined associations between presence of individual species, densities, or concurrent carriage of all species combination with respiratory diseases including clinical pneumonia, pneumonia with normal chest radiography (CXR) and endpoint pneumonia. Results Individual carriage, and NP density, of Sp, Hi, or Mc, but not Sa, or Nm, was significantly associated with febrile ARI and clinical pneumonia when compared to febrile non-ARI episodes. Density was also significantly increased in severe pneumonia when compared to mild URTI (Sp, p<0.002; Hi p<0.001; Mc, p = 0.014). Accordingly, concurrent carriage of Sp+, Hi+, and Mc+, in the absence of Sa- and Nm-, was significantly more prevalent in children with ARI (p = 0.03), or clinical pneumonia (p<0.001) than non-ARI, and in children with clinical pneumonia (p = 0.0007) than URTI. Furthermore, Sp+, Hi+, and Mc+ differentiated children with pneumonia with normal CXR, or endpoint pneumonia, from those with URTI, and non-ARI cases. Conclusions Concurrent NP carriage of Sp, Hi, and Mc was a predictor of clinical pneumonia and identified children with pneumonia with normal CXR and endpoint pneumonia from those with febrile URTI, or non-ARI episodes. PMID:27907156

Measurement of body temperature in normothermic and febrile rats: Limitations of using rectal thermometry.

PubMed

Dangarembizi, Rachael; Erlwanger, Kennedy H; Mitchell, Duncan; Hetem, Robyn S; Madziva, Michael T; Harden, Lois M

2017-10-01

Stress-induced hyperthermia following rectal thermometry is reported in normothermic rats, but appears to be muted or even absent in febrile rats. We therefore investigated whether the use of rectal thermometry affects the accuracy of temperature responses recorded in normothermic and febrile rats. Using intra-abdominally implanted temperature-sensitive radiotelemeters we measured the temperature response to rectal temperature measurement in male Sprague Dawley rats (~200g) injected subcutaneously with Brewer's yeast (20ml/kg of a 20% Brewer's yeast solution=4000mg/kg) or saline (20ml/kg of 0.9% saline). Rats had been pre-exposed to, or were naive to rectal temperature measurement before the injection. The first rectal temperature measurement was taken in the plateau phase of the fever (18h after injection) and at hourly intervals thereafter. In normothermic rats, rectal temperature measurement was associated with an increase in abdominal temperature (0.66±0.27°C) that had a rapid onset (5-10min), peaked at 15-20min and lasted for 35-50min. The hyperthermic response to rectal temperature measurement was absent in febrile rats. Exposure to rectal temperature measurement on two previous occasions did not reduce the hyperthermia. There was a significant positive linear association between temperatures recorded using the two methods, but the agreement interval identified that rectal temperature measured with a thermocouple probe could either be 0.7°C greater or 0.5°C lower than abdominal temperature measured with radiotelemeter. Thus, due to stress-induced hyperthermia, rectal thermometry does not ensure accurate recording of body temperature in short-spaced, intermittent intervals in normothermic and febrile rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison between febrile and afebrile seizures associated with mild rotavirus gastroenteritis.

PubMed

Kang, Ben; Kim, Dong Hyun; Hong, Young Jin; Son, Byong Kwan; Kim, Dong Wook; Kwon, Young Se

2013-09-01

We aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population. Medical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; 'no seizure' (NS: patients without seizure), 'febrile seizure' (FS: patients with fever during seizure), 'afebrile seizure' (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis. Among the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3±0.8 vs. 2.8±1.0 days; p<0.0001). A single seizure attack was significantly higher in the AFS group (3.0±1.6 vs. 1.7±1.0 episodes; p=0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p=0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period. Despite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Fever-Induced Brugada Syndrome Is More Common Than Previously Suspected: A Cross-Sectional Study from an Endemic Area.

PubMed

Rattanawong, Pattara; Vutthikraivit, Wasawat; Charoensri, Attawit; Jongraksak, Tanawat; Prombandankul, Awapa; Kanjanahattakij, Napatt; Rungaramsin, Sakda; Wisaratapong, Treechada; Ngarmukos, Tachapong

2016-03-01

Brugada syndrome (BrS) is defined as presenting of type-1 Brugada pattern (BrP). BrS can also be induced by fever. This study demonstrated a highest prevalence of fever-induced BrS ever reported. During May 2014, febrile (oral temperature ≥ 38 °C) and nonfebrile patients underwent standard and high leads (V1 and V2 at 2nd intercostal space) electrocardiogram. Risk factor and cardiac symptoms were recorded. Patients with a persistent of type-1 BrP after fever had subsided were excluded. The prevalence of BrS, type-2 BrP and early repolarization pattern (ERP) were demonstrated. A total of 401 patients, 152 febrile, and 249 nonfebrile, were evaluated. BrS was identified in six febrile patients (five males and one female) and two males in nonfebrile patients. The study demonstrated higher prevalence of BrS in febrile group compared to nonfebrile group (4.0% vs 0.8%, respectively, P = 0.037). Among fever-induced BrS patients, three patients (50.0%) experienced cardiac symptoms before and at the time of presentation and two patients (33.3%) had history of first-degree relative sudden death. No ventricular arrhythmia was observed. All of type-1 BrP disappeared after fever had subsided. We found no difference in prevalence of type-2 BrP in febrile and nonfebrile group (2.0% vs 2.8%, respectively, P > 0.05) as well as ERP (3.3% vs 6.4%, respectively, P > 0.05). Our study showed a highest prevalence of fever induced BrS ever reported. A larger study of prevalence, risk stratification, genetic test and management of fever-induced BrS should be done, especially in an endemic area. © 2015, Wiley Periodicals, Inc.

Time to antibiotics and outcomes in cancer patients with febrile neutropenia

PubMed Central

2014-01-01

Background Febrile neutropenia is an oncologic emergency. The timing of antibiotics administration in patients with febrile neutropenia may result in adverse outcomes. Our study aims to determine time-to- antibiotic administration in patients with febrile neutropenia, and its relationship with length of hospital stay, intensive care unit monitoring, and hospital mortality. Methods The study population was comprised of adult cancer patients with febrile neutropenia who were hospitalized, at a tertiary care hospital, between January 2010 and December 2011. Using Multination Association of Supportive Care in Cancer (MASCC) risk score, the study cohort was divided into high and low risk groups. A multivariate regression analysis was performed to assess relationship between time-to- antibiotic administration and various outcome variables. Results One hundred and five eligible patients with median age of 60 years (range: 18–89) and M:F of 43:62 were identified. Thirty-seven (35%) patients were in MASCC high risk group. Median time-to- antibiotic administration was 2.5 hrs (range: 0.03-50) and median length of hospital stay was 6 days (range: 1–57). In the multivariate analysis time-to- antibiotic administration (regression coefficient [RC]: 0.31 days [95% CI: 0.13-0.48]), known source of fever (RC: 4.1 days [95% CI: 0.76-7.5]), and MASCC high risk group (RC: 4 days [95% CI: 1.1-7.0]) were significantly correlated with longer hospital stay. Of 105 patients, 5 (4.7%) died & or required ICU monitoring. In multivariate analysis no variables significantly correlated with mortality or ICU monitoring. Conclusions Our study revealed that delay in antibiotics administration has been associated with a longer hospital stay. PMID:24716604

Association of Acetaminophen and Ibuprofen Use With Wheezing in Children With Acute Febrile Illness.

PubMed

Matok, Ilan; Elizur, Arnon; Perlman, Amichai; Ganor, Shani; Levine, Hagai; Kozer, Eran

2017-03-01

Many infants and children receive acetaminophen and/or ibuprofen during febrile illness. Previously, some studies have linked acetaminophen and ibuprofen use to wheezing and exacerbation of asthma symptoms in infants and children. To assess whether acetaminophen or ibuprofen use are associated with wheezing in children presenting to the emergency department (ED) with febrile illness. This was a cross-sectional study of children who presented with fever to the pediatric ED between 2009 and 2013. The data were collected from questionnaires and from the children's medical files. Patients with wheezing in the ED were compared with nonwheezing patients. Associations between medication use and wheezing were assessed using univariate and multivariate analyses. The multivariate analysis adjusted for potential confounding variables (ie, age, atopic dermatitis, allergies, smoking, antibiotics use, etc) via propensity scores. During the study period, 534 children admitted to the ED met our inclusion criteria, of whom 347 (65%) were included in the study. The use of acetaminophen was similar in children diagnosed with wheezing compared with those without wheezing (n = 39, 81.3%, vs n = 229, 82.7%, respectively). Ibuprofen use was significantly lower in children diagnosed with wheezing (n = 22, 52.4%, vs n = 168, 69.4%, respectively). In multivariate analysis, acetaminophen was not associated with a higher rate of wheezing during acute febrile illness (adjusted odds ratio [OR] = 0.76, 95% CI = 0.24- 2.39), whereas ibuprofen was associated with a lower risk of wheezing (adjusted OR = 0.36, 95% CI = 0.13-0.96). Our study suggests that acetaminophen and ibuprofen are not associated with increased risk for wheezing during acute febrile illness.

Safety of Early Discharge for Low-Risk Patients With Febrile Neutropenia: A Multicenter Randomized Controlled Trial

PubMed Central

Talcott, James A.; Yeap, Beow Y.; Clark, Jack A.; Siegel, Robert D.; Loggers, Elizabeth Trice; Lu, Charles; Godley, Paul A.

2011-01-01

Purpose Febrile neutropenia commonly complicates cancer chemotherapy. Outpatient treatment may reduce costs and improve patient comfort but risk progression of undetected medical problems. Patients and Methods By using our validated algorithm, we identified medically stable inpatients admitted for febrile neutropenia (neutrophils < 500/μL) after chemotherapy and randomly assigned them to continued inpatient antibiotic therapy or early discharge to receive identical antibiotic treatment at home. Our primary outcome was the occurrence of any serious medical complication, defined as evidence of medical instability requiring urgent medical attention. Results We enrolled 117 patients with 121 febrile neutropenia episodes before study termination for poor accrual. We excluded five episodes as ineligible and three because of inadequate documentation of the study outcome. Treatment groups were clinically similar, but sociodemographic imbalances occurred because of block randomization. The median presenting absolute neutrophil count was 100/μL. Hematopoietic growth factors were used in 38% of episodes. The median neutropenia duration was 4 days (range, 1 to 15 days). Five outpatients were readmitted to the hospital. Major medical complications occurred in five episodes (8%) in the hospital arm and four (9%) in the home arm (95% CI for the difference, −10% to 13%; P = .56). No study patient died. Patient-reported quality of life was similar on both arms. Conclusion We found no evidence of adverse medical consequences from home care, despite a protocol designed to detect evidence of clinical deterioration. These results should reassure clinicians who elect to treat rigorously characterized low-risk patients with febrile neutropenia in suitable outpatient settings with appropriate surveillance for unexpected clinical deterioration. PMID:21931024

Bacterial infection profiles in lung cancer patients with febrile neutropenia

PubMed Central

2011-01-01

Background The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. Methods We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm3) and fever (temperature > 38.3°C). Results The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm3. Conclusion Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population. PMID:21707992

Efficacy and safety of tazobactam/piperacillin as an empirical treatment for the patients of adult and child with febrile neutropenia in Japan.

PubMed

Tamura, Kazuo; Akiyama, Nobu; Kanda, Yoshinobu; Saito, Masahiro

2015-09-01

Tazobactam/piperacillin (4.5 g for adults and 90 mg/kg body weight for children, every 6 h) was administered to Japanese patients with febrile neutropenia to evaluate its defervescence and clinical efficacy and safety. The pharmacokinetics in children were also examined. Defervescence efficacy at day 4 of the treatment was achieved in 50.0% of 94 adult and 62.5% of 8 pediatric patients, respectively. The defervescence efficacy rate in relation to the neutrophil count in adults was 37.5% for the patients with a neutrophil count of less than 100/μL and 62.5% for that between 100 and 500/μL. The clinical efficacy rate at day 7 and at the end or discontinuation of the treatment was 79.6% and 59.1% in adult patients, respectively, and 57.1% and 75.0% in pediatric patients, respectively. Fifteen strains of causative bacteria were isolated in 13 adult patients at baseline. All strains were eradicated within 4 days of the treatment. The side effects that occurred in adult and pediatric patients during the treatment were all known and not specific to febrile neutropenia patients. The pharmacokinetics profiles of tazobactam/piperacillin in children with febrile neutropenia are unlikely to be different from those in children with a common bacterial infection and without any immunosuppressive conditions. The study results in Japanese patients with febrile neutropenia demonstrate that tazobactam/piperacillin treatment is efficacious and safe in adults. As for pediatric patients, given the limited number of cases studied, further investigation is needed (Clinical trial number: Japic CTI-121728). Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in lymphoma patients.

PubMed

Lathia, Nina; Isogai, Pierre K; De Angelis, Carlo; Smith, Thomas J; Cheung, Matthew; Mittmann, Nicole; Hoch, Jeffrey S; Walker, Scott

2013-08-07

Febrile neutropenia is a serious toxicity of cancer chemotherapy that is usually treated in hospital. We assessed the cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in diffuse large B-cell lymphoma (DLBCL) patients undergoing chemotherapy. We used a Markov model that followed patients through induction chemotherapy to compare the three prophylaxis strategies: 1) no primary prophylaxis against febrile neutropenia; 2) primary prophylaxis with 10 days of filgrastim therapy; and 3) primary prophylaxis with a single dose of pegfilgrastim. The target population was a hypothetical cohort of 64-year-old men and women with DLBCL. Data sources included published literature and current clinical practice. The analysis was conducted from a publicly funded health-care system perspective. The main outcome measures included costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). In the base-case analysis, costs associated with no primary prophylaxis, primary prophylaxis with 10 days of filgrastim, and primary prophylaxis with pegfilgrastim were CaD $7314, CaD $13947, and CaD $16290, respectively. The QALYs associated with the three strategies were 0.2004, 0.2015, and 0.2024, respectively. The ICER for the filgrastim vs no primary prophylaxis strategy was CaD $5796000 per QALY. The ICER for the pegfilgrastim vs filgrastim primary prophylaxis strategy was CaD $2611000 per QALY. All one-way sensitivity analyses yielded ICERs greater than CaD $400000 per QALY. Cost-effectiveness acceptability curves show that 20.0% of iterations are cost-effective at a willingness-to-pay threshold of CaD $1595000 for the filgrastim strategy and CaD $561000 for the pegfilgrastim strategy. Primary prophylaxis against febrile neutropenia with either filgrastim or pegfilgrastim is not cost-effective in DLBCL patients.

Bacterial infection profiles in lung cancer patients with febrile neutropenia.

PubMed

Lanoix, Jean-Philippe; Pluquet, Emilie; Lescure, Francois Xavier; Bentayeb, Houcine; Lecuyer, Emmanuelle; Boutemy, Marie; Dumont, Patrick; Jounieaux, Vincent; Schmit, Jean Luc; Dayen, Charles; Douadi, Youcef

2011-06-27

The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm(3)) and fever (temperature > 38.3°C). The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm(3). Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.

Can complications in febrile neutropenia be predicted? Report from a developing country.

PubMed

Oberoi, Sapna; Das, Anirban; Trehan, Amita; Ray, Pallab; Bansal, Deepak

2017-11-01

Febrile neutropenia (FN) is an important cause of morbidity and mortality in children with acute lymphoblastic leukemia (ALL). We aimed to look at complications in febrile neutropenia and to derive a risk model for developing complications from the variables predicting complications. Children on treatment for ALL, presenting with FN, were prospectively enrolled over a period of 1 year. Their clinical presentation, course during hospital stay, and outcomes were recorded. Complications recorded included septic shock, pneumonia requiring invasive or non-invasive ventilation, renal failure, neutropenic enterocolitis, encephalopathy, congestive heart failure, and bleeding manifestations. There were 320 episodes of FN among 176 patients. Complications occurred during 73 (22.8%) episodes. Time since last chemotherapy ≤7 days [OR 2.2 (1-4.5)], clinical focus of infection [OR 2.7 (1.3-5.5)], undernutrition [OR 2.5 (1.1-5.5)], absolute neutrophil count (ANC) ≤ 100/μL [OR 2.8 (1.3-5.9)], and C-reactive protein (CRP) > 60 mg/L at admission [OR 13.3 (5.2-33.8)] were independent predictors of complications. A risk model (total score = 13) was developed based on these predictors. Children with score of ≥7 had 17.2 (7.7-38.6) odds of developing complications as compared to those with score <7. Score of <7 predicted children at lower risk of complications [sensitivity 88% (78.2-93.8%), specificity 72.5% (65.7-78.4%), PPV 53.6% (44.3-62.6%), NPV 94.4% (89.3-97.1%)]. Complications during febrile neutropenia are high in a developing country setup. A risk score model based on identified risk factors can possibly help in recognizing low-risk febrile neutropenic children at admission.

[Mexidol in treatment of children with generalized epilepsy and febrile seizures].

PubMed

Natriashvili, G; Natriashvili, S; Kapanadze, N

2005-05-01

The aim of our study was to estimate the role of Mexidol in ceasing of epileptic fits and improving electroencephalographic (EEG) pathological patterns in children. 120 patients with generalized epilepsy (from 4 to 16 years old) were investigated. All patients were treated by Depakin chrono 30 mg/kg. Children were divided into 2 groups: 1st--study group consisted of 60 children with combined treatment with Depakin and Mexidol (5 mg/kg). In the control group (60 children) treatment was performed only by Depakin. 100 children with the first episode of febrile seizures (from 6 months to 4 years old) were investigated. 50 children composed the study group with monotheraphy by Mexidol and 50 patients--the control group, without any treatment. The EEG examination was done by computer EEG Topography "Brain Surveyor Saico". Using Depakin in combination with Mexidol in the study group of patients with generalized epilepsy, improvement of clinical picture of disease and normalization of EEG patterns in 93% of cases has been observed. In the study group of patients with febrile seizures, normalization of EEG pathological patterns was observed in 82% cases and in 18% its improvement was seen. The relapse of seizures at high temperature was observed in 3 patients. In control group EEG patterns were improved only in 20%, in 48% no positive effect was observed and in 41% the worsening of EEG findings was seen. The relapse of febrile seizures was observed in 26 cases. Mexidol titrated to the target doze of 5mg/kg may be effective in combination with Depakin for treatment of patients with generalized epilepsy and as monotherapy in patients with first episode of febrile seizures.

AUV Positioning Method Based on Tightly Coupled SINS/LBL for Underwater Acoustic Multipath Propagation.

PubMed

Zhang, Tao; Shi, Hongfei; Chen, Liping; Li, Yao; Tong, Jinwu

2016-03-11

This paper researches an AUV (Autonomous Underwater Vehicle) positioning method based on SINS (Strapdown Inertial Navigation System)/LBL (Long Base Line) tightly coupled algorithm. This algorithm mainly includes SINS-assisted searching method of optimum slant-range of underwater acoustic propagation multipath, SINS/LBL tightly coupled model and multi-sensor information fusion algorithm. Fuzzy correlation peak problem of underwater LBL acoustic propagation multipath could be solved based on SINS positional information, thus improving LBL positional accuracy. Moreover, introduction of SINS-centered LBL locating information could compensate accumulative AUV position error effectively and regularly. Compared to loosely coupled algorithm, this tightly coupled algorithm can still provide accurate location information when there are fewer than four available hydrophones (or within the signal receiving range). Therefore, effective positional calibration area of tightly coupled system based on LBL array is wider and has higher reliability and fault tolerance than loosely coupled. It is more applicable to AUV positioning based on SINS/LBL.

AUV Positioning Method Based on Tightly Coupled SINS/LBL for Underwater Acoustic Multipath Propagation

PubMed Central

Zhang, Tao; Shi, Hongfei; Chen, Liping; Li, Yao; Tong, Jinwu

2016-01-01

This paper researches an AUV (Autonomous Underwater Vehicle) positioning method based on SINS (Strapdown Inertial Navigation System)/LBL (Long Base Line) tightly coupled algorithm. This algorithm mainly includes SINS-assisted searching method of optimum slant-range of underwater acoustic propagation multipath, SINS/LBL tightly coupled model and multi-sensor information fusion algorithm. Fuzzy correlation peak problem of underwater LBL acoustic propagation multipath could be solved based on SINS positional information, thus improving LBL positional accuracy. Moreover, introduction of SINS-centered LBL locating information could compensate accumulative AUV position error effectively and regularly. Compared to loosely coupled algorithm, this tightly coupled algorithm can still provide accurate location information when there are fewer than four available hydrophones (or within the signal receiving range). Therefore, effective positional calibration area of tightly coupled system based on LBL array is wider and has higher reliability and fault tolerance than loosely coupled. It is more applicable to AUV positioning based on SINS/LBL. PMID:26978361

Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression

PubMed Central

Rielland, Maïté; Cantor, David J.; Graveline, Richard; Hajdu, Cristina; Mara, Lisa; de Diego Diaz, Beatriz; Miller, George; David, Gregory

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional therapeutic approaches. We previously demonstrated that the histone deacetylase–associated protein SIN3B is essential for oncogene-induced senescence in cultured cells. Here, using a mouse model of pancreatic cancer, we have demonstrated that SIN3B is required for activated KRAS-induced senescence in vivo. Surprisingly, impaired senescence as the result of genetic inactivation of Sin3B was associated with delayed PDAC progression and correlated with an impaired inflammatory response. In murine and human pancreatic cells and tissues, levels of SIN3B correlated with KRAS-induced production of IL-1α. Furthermore, evaluation of human pancreatic tissue and cancer cells revealed that Sin3B was decreased in control and PDAC samples, compared with samples from patients with pancreatic inflammation. These results indicate that senescence-associated inflammation positively correlates with PDAC progression and suggest that SIN3B has potential as a therapeutic target for inhibiting inflammation-driven tumorigenesis. PMID:24691445

Reciprocity in Vector Acoustics

DTIC Science & Technology

2017-03-01

and a phase function that accounts for grid spacing, ψ̂m(kz) = −2 j √ jR0 2πk sin(kz zs) * , 1 − k2z k2 + - 1 4 e j kz dz 2 , (A.4) where the...Equation (A.4) becomes ψ̂v (kz) = −2 j √ jR0 2πk [ j Az sin(kz[zs + ∆z]) − j Az sin(kz[zs − ∆z]) ] * , 1 − k2z k2 + - 1 4 e j kz dz 2 (A.7) When this...sin(kz zs) + A3 sin(kz[zs + 2∆z]) +A4 sin(kz[zs + 4∆z]) ] * , 1 − k2z k2 + - 1 4 e j kz dz 2 . With this starter field, MMPE outputs pressure, radial

Treatable Bacterial Infections Are Underrecognized Causes of Fever in Ethiopian Children

PubMed Central

Aarsland, Sara J.; Castellanos-Gonzalez, Alejandro; Lockamy, Kameron P.; Mulu-Droppers, Ruth; Mulu, Moges; White, A. Clinton; Cabada, Miguel M.

2012-01-01

Febrile illnesses remain a major cause of morbidity and mortality in resource-poor countries, but too often, tests are not available to determine the causes, leading to misdiagnosis and inappropriate treatment. To determine the cause of febrile illnesses, we recovered the malaria smears from 102 children presenting with fever to Soddo Christian Hospital in Wolaitta Soddo, Ethiopia. DNA was isolated from the smears and evaluated by real-time polymerase chain reaction. We identified pathogen DNA with probes for Plasmodium spp., Streptococcus pneumoniae, Rickettsia spp., Salmonella spp., and Borrelia spp. Overall, we showed that it is possible to isolate high-quality DNA and identify treatable pathogens from malaria blood smears. Furthermore, our data showed that bacterial pathogens (especially Pneumococcus, Rickettsia spp., and Borrelia spp.) are common and frequently unrecognized but treatable causes of febrile illnesses in Ethiopian children. PMID:22764303

Latinos and the Media. Focus "En Foco".

ERIC Educational Resources Information Center

Vasquez, Blanca, Ed.

1990-01-01

This issue focuses on Latin Americans and the media, with emphasis on portrayal of the Latin American in United States mass media. "Puerto Ricans and the Media: A Personal Statement" (B. Vasquez) recalls the author's experiences as a young girl in the New York City public schools and in an urban college. The critical importance of the…

Domestically Acquired Fascioliasis in Northern California

PubMed Central

Weisenberg, Scott A.; Perlada, David E.

2013-01-01

Two cases of domestically acquired fascioliasis are reported. Patient One was a 63-year-old male who developed a febrile illness 2 months after eating watercress in Marin County. Patient Two was a 38-year-old male who had eaten watercress with Patient One, and also developed a febrile illness. Both patients had eosinophilia and liver lesions on imaging. Diagnosis was made by serology and treatment was with triclabendazole. PMID:23836562

Malaria and Chikungunya Detected Using Molecular Diagnostics Among Febrile Kenyan Children.

PubMed

Waggoner, Jesse; Brichard, Julie; Mutuku, Francis; Ndenga, Bryson; Heath, Claire Jane; Mohamed-Hadley, Alisha; Sahoo, Malaya K; Vulule, John; Lefterova, Martina; Banaei, Niaz; Mukoko, Dunstan; Pinsky, Benjamin A; LaBeaud, A Desiree

2017-01-01

In sub-Saharan Africa, malaria is frequently overdiagnosed as the cause of an undifferentiated febrile illness, whereas arboviral illnesses are presumed to be underdiagnosed. Sera from 385 febrile Kenyan children, who presented to 1 of 4 clinical sites, were tested using microscopy and real-time molecular assays for dengue virus (DENV), chikungunya virus (CHIKV), malaria, and Leptospira . Malaria was the primary clinical diagnosis for 254 patients, and an arboviral infection (DENV or CHIKV) was the primary diagnosis for 93 patients. In total, 158 patients (41.0%) had malaria and 32 patients (8.3%) had CHIKV infections. Compared with real-time polymerase chain reaction, microscopy demonstrated a percent positive agreement of 49.7%. The percentage of malaria cases detected by microscopy varied significantly between clinical sites. Arboviral infections were the clinical diagnosis for patients on the Indian Ocean coast (91 of 238, 38.2%) significantly more often than patients in the Lake Victoria region (2 of 145, 1.4%; P < .001). However, detection of CHIKV infections was significantly higher in the Lake Victoria region (19 of 145 [13.1%] vs 13 of 239 [5.4%]; P = .012). The clinical diagnosis of patients with an acute febrile illness, even when aided by microscopy, remains inaccurate in malaria-endemic areas, contributing to inappropriate management decisions.

Infusional β-lactam antibiotics in febrile neutropenia: has the time come?

PubMed

Abbott, Iain J; Roberts, Jason A

2012-12-01

Febrile neutropenia presents a clinical challenge in which timely and appropriate antibiotic exposure is crucial. In the context of altered pharmacokinetics and rising bacterial resistance, standard antibiotic doses are unlikely to be sufficient. This review explores the potential utility of altered dosing approaches of β-lactam antibiotics to optimize treatment in febrile neutropenia. There is a dynamic relationship between the antibiotic, the infecting pathogen, and the host. Great advancements have been made in the understanding of the pharmacokinetic changes in critical illness and the pharmacodynamic relationships of antibiotics in these settings. Antibiotic treatment in febrile neutropenia is becoming increasingly difficult. Patients are of higher acuity, receive more intensive chemotherapy regimens leading to prolonged neutropenia, and are often exposed to multiple antibiotic courses. These patients display significant variability in antibiotic clearances and increases in volume of distribution compared with standard ward-based patients. Rising antibiotic resistance and a lack of new antibiotics in production have prompted alternative dosing strategies based on pharmacokinetic/pharmacodynamic data, such as extended or continuous infusions of β-lactam antibiotics, to maximize the likelihood of treatment success. A definitive study that describes a mortality benefit of such dosing regimens remains elusive and the theoretical advantages require testing in well designed clinical trials.

Febrile response to infection in the American alligator (Alligator mississippiensis).

PubMed

Merchant, Mark; Williams, Stephanie; Trosclair, Phillip L; Elsey, Ruth M; Mills, Kaili

2007-12-01

Temperature probes were inserted into the stomachs of juvenile American alligators (Alligator mississippiensis) maintained outdoors at ambient fluctuating temperatures. Internal body temperatures (T(b)) were measured every 15 min for two days, and then the alligators were injected with bacterial lipopolysaccharide (LPS), pyrogen-free saline, or left untreated. Alligators injected intraperitoneally with LPS exhibited maximum T(b)s 2.6+/-1.1 degrees C and 3.5+/-1.2 degrees C higher than untreated control animals on days one and two after treatment, respectively. T(b)s for these animals fell to within control ranges by day three postinjection. Similarly, mean preferred body temperatures (MPBTs) were significantly higher for LPS-injected alligators on days one (4.2+/-1.8 degrees C) and two (3.5+/-1.6 degrees C) after treatment. Intraperitoneal injection of heat-killed Aeromonas hydrophila, a gram-negative bacterium known to infect crocodilians, resulted in a fever while injection of Staphylococcus aureus (gram positive) did not elicit a febrile response. Injection of LPS in alligators maintained indoors in a constant temperature environment resulted in no increase in internal T(b). These results indicate that alligators did not exhibit a febrile response in the absence of a thermal gradient, and suggest that febrile responses observed are probably behavioral in nature.

Use and limitations of malaria rapid diagnostic testing by community health workers in war-torn Democratic Republic of Congo.

PubMed

Hawkes, Michael; Katsuva, Jean Paul; Masumbuko, Claude K

2009-12-23

Accurate and practical malaria diagnostics, such as immunochromatographic rapid diagnostic tests (RDTs), have the potential to avert unnecessary treatments and save lives. Volunteer community health workers (CHWs) represent a potentially valuable human resource for expanding this technology to where it is most needed, remote rural communities in sub-Saharan Africa with limited health facilities and personnel. This study reports on a training programme for CHWs to incorporate RDTs into their management strategy for febrile children in the Democratic Republic of Congo, a tropical African setting ravaged by human conflict. Prospective cohort study, satisfaction questionnaire and decision analysis. Twelve CHWs were trained to safely and accurately perform and interpret RDTs, then successfully implemented rapid diagnostic testing in their remote community in a cohort of 357 febrile children. CHWs were uniformly positive in evaluating RDTs for their utility and ease of use. However, high malaria prevalence in this cohort (93% by RDTs, 88% by light microscopy) limited the cost-effectiveness of RDTs compared to presumptive treatment of all febrile children, as evidenced by findings from a simplified decision analysis. CHWs can safely and effectively use RDTs in their management of febrile children; however, cost-effectiveness of RDTs is limited in zones of high malaria prevalence.

Use and limitations of malaria rapid diagnostic testing by community health workers in war-torn Democratic Republic of Congo

PubMed Central

2009-01-01

Background Accurate and practical malaria diagnostics, such as immunochromatographic rapid diagnostic tests (RDTs), have the potential to avert unnecessary treatments and save lives. Volunteer community health workers (CHWs) represent a potentially valuable human resource for expanding this technology to where it is most needed, remote rural communities in sub-Saharan Africa with limited health facilities and personnel. This study reports on a training programme for CHWs to incorporate RDTs into their management strategy for febrile children in the Democratic Republic of Congo, a tropical African setting ravaged by human conflict. Methods Prospective cohort study, satisfaction questionnaire and decision analysis. Results Twelve CHWs were trained to safely and accurately perform and interpret RDTs, then successfully implemented rapid diagnostic testing in their remote community in a cohort of 357 febrile children. CHWs were uniformly positive in evaluating RDTs for their utility and ease of use. However, high malaria prevalence in this cohort (93% by RDTs, 88% by light microscopy) limited the cost-effectiveness of RDTs compared to presumptive treatment of all febrile children, as evidenced by findings from a simplified decision analysis. Conclusions CHWs can safely and effectively use RDTs in their management of febrile children; however, cost-effectiveness of RDTs is limited in zones of high malaria prevalence. PMID:20028563

Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia--species distribution and susceptibility patterns.

PubMed

Miedema, Karin G E; Winter, Rik H L J; Ammann, Roland A; Droz, Sara; Spanjaard, Lodewijk; de Bont, Eveline S J M; Kamps, Willem A; van de Wetering, Marianne D; Tissing, Wim J E

2013-09-01

Infections are a major cause of morbidity and mortality in pediatric cancer patients. The aim of this study was to establish the microbiological spectrum and the susceptibility patterns of bacteremia-causing bacteria in pediatric cancer patients with febrile neutropenia in relation to the use of prophylactic and empirical antibiotics. We analyzed positive blood cultures of pediatric cancer patients presenting with febrile neutropenia between 2004 and 2011 in Groningen and Amsterdam (the Netherlands) and in Bern (Switzerland), using different antibiotic prophylactic and empirical regimens. A total of 156 patients with 202 bacteremias, due to 248 bacteria species, were enrolled. The majority (73%) of bacteremias were caused by Gram-positive bacteria. Gram-negative bacteria, especially Pseudomonas aeruginosa, were observed significantly more often in Bern, where no fluoroquinolone prophylaxis was used. Ciprofloxacin-resistant bacteria were cultured more often from patients who did receive ciprofloxacin prophylaxis, compared to the patients who did not (57 versus 11%, p = 0.044). Gram-positive bacteria predominated in this study. We showed that the use of prophylactic antibiotics in pediatric cancer patients was associated with increased resistance rates, which needs further study. The strategy for empiric antimicrobial therapy for febrile neutropenia should be adapted to local antibiotic resistance patterns.

Outpatient management of febrile neutropenia: time to revise the present treatment strategy.

PubMed

Carstensen, Mads; Sørensen, Jens Benn

2008-01-01

We reviewed medical literature on the efficacy and safety of outpatient versus hospital-based therapy of low-risk febrile neutropenia in adult cancer patients. A PubMed search for all studies evaluating the outpatient treatment of adults diagnosed with solid tumors who suffered from low-risk febrile neutropenia was completed; reference lists from identified articles also were used. In all, 10 trials were included in the analysis, which showed no significant difference in clinical failure rates and mortality for ambulatory regimens and standard hospital-based therapy. Subgroup analysis according to the type of fever episode showed no significant differences in clinical failure rates for fever of unknown origin and fever due to documented infections. Subgroup analyses in two independent trials identified an absolute neutrophil count < 100 cells/ mm3 as being predictive of outpatient treatment failure (P < 0.04). These findings need to be confirmed by further trials. Thus, outpatient management of adult cancer patients with low-risk febrile neutropenia is safe, effective, and comparable to standard hospital-based therapy. Patients at low risk are outpatients and are hemodynamically stable; they have no organ failure, they are able to take oral medications, and they do not suffer from acute leukemia. Low-risk prediction also may be based on the Multinational Association for Supportive Care in Cancer risk index.

Assessment and management of febrile neutropenia in emergency departments within a regional health authority—a benchmark analysis

PubMed Central

Szwajcer, D.; Czaykowski, P.; Turner, D.

2011-01-01

Objectives Febrile neutropenia is considered an oncologic emergency, for which prompt initiation of antibiotics is essential. Methods We conducted a retrospective cohort study for the 2006 calendar year involving all adult oncology patients presenting with febrile neutropenia to a regional health authority’s emergency departments. The objective was to determine the time from triage to antibiotic administration and its impact on patient outcomes. Results We identified 68 patients presenting with febrile neutropenia, most of whom (76%) were seen in tertiary care centers. Of those patients, 65% were triaged to be seen within 15 minutes of arrival in the emergency room; however, the median time to reassessment was 57 minutes. The median time from triage to antibiotic administration was 5 hours (range: 1.23–22.8 hours). No increased risk of death or increased length of hospital stay was associated with delayed antibiotic administration. Older patients and patients without caregiver support were more likely to experience delayed antibiotic administration (odds ratio: 3.8 and 12.7 respectively). Conclusions We were not able to show a deleterious effect of delay in antibiotic administration, but our analysis identified several points at which patient flow through the emergency room could be improved. PMID:22184489

Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis.

PubMed

van der Velden, Walter J F M; Herbers, Alexandra H E; Netea, Mihai G; Blijlevens, Nicole M A

2014-11-01

Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as 'febrile neutropenia', but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or 'mucositis'. MBI creates a port-de-entrée for resident micro-organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host-microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept 'febrile neutropenia' alone may no longer suffice and a new concept 'febrile mucositis' should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host-microbe interactions arising from cytotoxic therapy-induced tissue damage in order to reduce fever in neutropenic patients with cancer. © 2014 John Wiley & Sons Ltd.

[Fever profile of febrile neutropenia in patients treated with cancer chemotherapy for hematological malignancies].

PubMed

Tamai, Yotaro; Imataki, Osamu; Kawakami, Kimihiro

2010-05-01

It is important to diagnose infectious events in cancer patients during chemotherapy. Since many of them have complications of febrile neutropenia (FN), determining its cause is critical for their treatment course. We analyzed all febrile events (>38.0 degrees C, single axillary temperature) in hospitalized cancer patients treated at Shizuoka Cancer Center over a period of 8 months. Based on the clinical presentation at the onset, we estimated the cause of fever and classified it as infection, tumor fever, immunologic reaction or unknown. Clinical presentations found at the onset of FN were categorized into 4 groups: (1) oral mucositis, and (2) respiratory, (3) gastrointestinal and (4) cutaneous findings. We detected 85 febrile episodes (median age 58, range 26 approximately 86; 37 males and 48 females). Neutropenia was observed (500/mL) in 52. 9% (45/85) of the patients and clinical symptoms were detected in 74.1% (63/85). In eleven of 18 infection-proven cases, we successfully predicted the infection focus at the onset of fever. Multivariate analysis revealed that initial high fever, antimicrobial prophylaxis, cutaneous findings and severe neutropenia were important influencing factors in predicting infectious disease during FN. Physical examination can support the diagnosis of the cause of fever in FN patients.

Aspergilosis cervical con diseminación al sistema nervioso central. Presentación de un caso y revisión de bibliografía

PubMed Central

Vergara, Guillermo Enrique; Roura, Natalia; del Castillo, Marcelo; Mora, Andrea; Alcorta, Santiago Condomi; Mormandi, Rubén; Cervio, Andrés; Salvat, Jorge

2015-01-01

Introducción: la Aspergilosis Invasiva (AI) del Sistema Nervioso Central (SNC) es infrecuente y ocurre generalmente en pacientes inmunocomprometidos. Puede presentarse con cuadros de meningitis, aneurismas micóticos, infartos o abscesos. Es una infección con pronóstico reservado y puede afectar el SNC de forma primaria o secundaria a partir de un foco que se disemina por vía hematógena. Presentamos el caso de un paciente con AI con invasión primaria a nivel óseo y diseminación posterior al cerebro. Caso clínico: Paciente masculino de 25 años con diagnóstico de leucemia linfática aguda en tratamiento quimioterápico que presentó neumonitis por metotrexate por lo que inicia tratamiento con corticoides. Posteriormente agregó cervicalgia y con el diagnóstico de osteomielitis cervical se realiza punción bajo tomografía computada (TC) sin aislarse gérmenes. Se colocó Halo Vest e inició tratamiento antibiótico empírico. Posteriormente presentó afasia de expresión secundaria a lesión frontal izquierda. Se realizó evacuación de absceso cerebral aislando A. fumigatus. El tratamiento antibiótico específico posterior permitió una buena respuesta clínica y radiológica. Conclusión: La presencia de lesiones en el SNC de pacientes inmunocomprometidos debe incluir a las micosis como diagnóstico diferencial. La evacuación quirúrgica permite llegar rápidamente al diagnóstico mejorando la respuesta posterior al tratamiento antibiótico. Para evaluar la respuesta terapéutica y posibles recaídas se debe realizar un seguimiento periódico clínico radiológico. Palabras clave: Aspergilosis cerebral; Aspergilosis cervical; Aspergilosis invasiva; Voriconazol. PMID:26600985

Administration of SIN-1 induces guinea pig airway hyperresponsiveness through inactivation of airway neutral endopeptidase.

PubMed

Kanazawa, H; Hirata, K; Yoshikawa, J

1999-12-01

Peroxynitrite plays an important role in the pathogenesis of airway inflammation. We have already found that peroxynitrite may contribute to decreased beta(2)-adrenoceptor responses in airway smooth muscle. However, it is not known whether peroxynitrite can alter neutral endopeptidase (EC 3.4.24.11; NEP) activity in the airways. This study was designed to determine whether peroxynitrite induces airway hyperresponsiveness to substance P (SP) and endothelin-1 (ET-1) through the inactivation of airway NEP. We examined whether the administration of S-morpholinosydnonimine (SIN-1), a compound that releases peroxynitrite, increased bronchoconstrictor responses to SP and ET-1 in anesthetized guinea pigs. In addition, we assayed NEP activity in the airways of SIN-1-exposed guinea pigs. Though SIN-1 (10(-7) M) alone had no effect on pulmonary resistance, pretreatment with SIN-1 significantly enhanced SP- and ET-1-induced bronchoconstriction. Pretreatment with phosphoramidon, an NEP inhibitor, also enhanced SP- and ET-1-induced bronchoconstriction. However, simultaneous administration of phosphoramidon and SIN-1 had no additive effect on SP- and ET-1-induced bronchoconstriction. Peroxynitrite formation by SIN-1 was completely inhibited by N-acetylcysteine (NAC) and glutathione (GSH) in vitro, and pretreatment with NAC and GSH significantly reversed the potentiation by SIN-1 of SP-induced bronchoconstriction. In addition, the NEP activity of the trachea after SIN-1 exposure was significantly reduced compared to the level in control guinea pigs (solvent for SIN-1: 30.0+/-4.2 fmol.min(-1).mg tissue(-1); 10(-7) M SIN-1; 15.5+/-4.5 fmol.min(-1).mg tissue(-1), p<0.05). These findings suggest that peroxynitrite induces airway hyperresponsiveness to SP and ET-1 through the inactivation of airway NEP, and that peroxynitrite is an important mediator of the alterations in airway functions.

Measurement of sin2θw and ϱ in deep inelastic neutrino-nucleon scattering

NASA Astrophysics Data System (ADS)

Reutens, P. G.; Merritt, F. S.; Macfarlane, D. B.; Messner, R. L.; Novikoff, D. B.; Purohit, M. V.; Blair, R. E.; Sciulli, F. J.; Shaevitz, M. H.; Fisk, H. E.; Fukushima, Y.; Jin, B. N.; Kondo, T.; Rapidis, P. A.; Yovanovitch, D. D.; Bodek, A.; Coleman, R. N.; Marsh, W. L.; Fackler, O. D.; Jenkins, K. A.

1985-03-01

We describe a high statistics measurement from deep inelastic neutrino-nucleon scattering of the electroweak parameters ϱ and sin2θw, performed in the Fermilab narrow-band neutrino beam. Our measurement uses a radius-dependent cut in y = EH/Ev which reduces the systematic error in sin2θw, and incorporates electromagnetic and electroweak radiative corrections. In a renormalization scheme where sin2θw ≡ 1-m2W/m2Z, a value of sin2θw = 0.242+/-0.011+/-0.005 is obtained fixing ϱ = 1. If both sin2θw and ϱ are allowed to vary in a fit to our data, we measure ϱ = 0.991 +/- 0.025 +/- 0.009. Present address: IBM Thomas J. Watson Research Center, PO Box 218, Yorktown Heights, NY 10598, USA.

Multiple histone deacetylases are recruited by corepressor Sin3 and contribute to gene repression mediated by Opi1 regulator of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae.

PubMed

Grigat, Mathias; Jäschke, Yvonne; Kliewe, Felix; Pfeifer, Matthias; Walz, Susanne; Schüller, Hans-Joachim

2012-06-01

Yeast genes of phospholipid biosynthesis are negatively regulated by repressor protein Opi1 when precursor molecules inositol and choline (IC) are available. Opi1-triggered gene repression is mediated by recruitment of the Sin3 corepressor complex. In this study, we systematically investigated the regulatory contribution of subunits of Sin3 complexes and identified Pho23 as important for IC-dependent gene repression. Two non-overlapping regions within Pho23 mediate its direct interaction with Sin3. Previous work has shown that Sin3 recruits the histone deacetylase (HDAC) Rpd3 to execute gene repression. While deletion of SIN3 strongly alleviates gene repression by IC, an rpd3 null mutant shows almost normal regulation. We thus hypothesized that various HDACs may contribute to Sin3-mediated repression of IC-regulated genes. Indeed, a triple mutant lacking HDACs, Rpd3, Hda1 and Hos1, could phenocopy a sin3 single mutant. We show that these proteins are able to contact Sin3 in vitro and in vivo and mapped three distinct HDAC interaction domains, designated HID1, HID2 and HID3. HID3, which is identical to the previously described structural motif PAH4 (paired amphipathic helix), can bind all HDACs tested. Chromatin immunoprecipitation studies finally confirmed that Hda1 and Hos1 are recruited to promoters of phospholipid biosynthetic genes INO1 and CHO2.

Prostate Cancer Clinical Trials Group: The University of Michigan Site

DTIC Science & Technology

2011-04-01

monotherapy, 10% of the 41 patients on the mitoxantrone/prednisone second-line arm experienced febrile neutropenia , and 9% of the 56 patients on this...study of the combination (with pegfilgrastim support) experi- enced febrile neutropenia . It is important to note, however, that this margin of safety can...15.9). Thirty-two percent of patients experienced grade 3 of 4 neutropenia , and 11% experienced grade 3 or higher neutropenic infections, including 1

Consensus on diagnosis and empiric antibiotic therapy of febrile neutropenia

PubMed Central

Giurici, Nagua; Zanazzo, Giulio A.

2011-01-01

Controversial issues on the management of empiric therapy and diagnosis of febrile neutropenia (FN) were faced by a Consensus Group of the Italian Association of Pediatric Hematology-Oncology (AIEOP). In this paper we report the suggestions of the consensus process regarding the role of aminoglycosides, glycopeptides and oral antibiotics in empiric therapy of FN, the rules for changing or discontinuing the therapy as well as the timing of the blood cultures. PMID:21647277

Prospective Cohort Study with Active Surveillance for Fever in Four Dengue Endemic Countries in Latin America

PubMed Central

Dayan, Gustavo; Arredondo, Jose L.; Carrasquilla, Gabriel; Deseda, Carmen C.; Dietze, Reynaldo; Luz, Kleber; Costa, Maria Selma N.; Cunha, Rivaldo V.; Rey, Luis C.; Morales, Javier; Reynales, Humberto; Miranda, Maria; Zambrano, Betzana; Rivas, Enrique; Garbes, Pedro; Noriega, Fernando

2015-01-01

To prepare for a Phase III dengue vaccine efficacy trial, 20 investigational sites were selected for this observational study to identify dengue infections in a closed cohort (N = 3,000 children 9–16 years of age). Of 255 acute febrile episodes experienced by 235 children, 50 (21.3%) were considered serologically probable dengue, and 18 (7.7%) were considered virologically confirmed (i.e., dengue NS1 antigen positive) dengue cases. Considering the disease-free and at-risk period from study start to onset of symptoms, the overall incidence density of acute febrile episodes was 17.7 per 100 person-years of follow-up, ranging from 15.3 in Colombia to 22.0 in Puerto Rico. This study showed that all sites were capable of capturing and following up acute febrile episodes within a specific timeframe among the established cohort and to detect dengue cases. PMID:26013373

A comparison of technologies used for estimation of body temperature.

PubMed

Mangat, Jasdip; Standley, Thomas; Prevost, Andrew; Vasconcelos, Joana; White, Paul

2010-09-01

Body temperature measurement is an important clinical parameter. The performance of a number of non-invasive thermometers was measured by comparing intra- and inter-operator variability (n = 100) and clinical accuracy (n = 61). Variability was elevated in febrile compared to normothermic subjects for axillary and oral electronic contact thermometer measures and a temporal artery thermometer (p < 0.001 for both). Temporal artery thermometry and one mode of an infrared tympanic thermometer demonstrated significant clinical inaccuracy (p < 0.001 for both). Electronic contact thermometer repeatability and reproducibility are highly variable in febrile adults both in the axilla and oral cavity. Infrared thermometry of the skin over the superficial temporal artery is unreliable for measuring core body temperature, particularly in febrile subjects and patients in theatre. The infrared tympanic thermometers tested are acceptable for clinical practice; however, care should be exercised with the different modes of operation offered.

Urinary tract infections in children after renal transplantation.

PubMed

John, Ulrike; Kemper, Markus J

2009-06-01

Urinary tract infections (UTI) after pediatric kidney transplantation (KTX) are an important clinical problem and occur in 15-33% of patients. Febrile UTI, whether occurring in the transplanted kidney or the native kidney, should be differentiated from afebrile UTI. The latter may cause significant morbidity and is usually associated with acute graft dysfunction. Risk factors for (febrile) UTI include anatomical, functional, and demographic factors as well as baseline immunosuppression and foreign material, such as catheters and stents. Meticulous surveillance, diagnosis, and treatment of UTI is important to minimize acute morbidity and compromise of long-term graft function. In febrile UTI, parenteral antibiotics are usually indicated, although controlled data are not available. As most data concerning UTI have been accumulated retrospectively, future prospective studies have to be performed to clarify pathogenetic mechanisms and risk factors, improve prophylaxis and treatment, and ultimately optimize long-term renal graft survival.

Parental weighting of seizure risks vs. fever risks in vaccination tradeoff decisions.

PubMed

Zikmund-Fisher, Brian J; Wittenberg, Eve; Lieu, Tracy A

2016-12-07

As part of a survey of about vaccination beliefs, a nationally representative sample of parents of young children answered a series of tradeoff questions that asked them to choose between two vaccination approaches that differed in terms of risks of vaccine complications, number of injections, and/or vaccine effectiveness. Most parents were willing to have their children endure more injections, and many were willing to forgo disease protection, in order to reduce the rare chance of febrile seizures. Yet, most parents were unwilling to trade disease protection to reduce the risk of fever alone, even though this is correlated with the risk of febrile seizures. Vaccine risk communications need to address the heightened emotional weight that parents give to febrile seizure risk, even when the rarity of such events is explicit. Copyright © 2016 Elsevier Ltd. All rights reserved.

Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia.

PubMed

Gómez Raposo, César; Pinto Marín, Alvaro; González Barón, Manuel

2006-10-01

The hematopoietic growth factors (HGFs) are a family of glycoproteins which plays a major role in the proliferation, differentiation, and survival of primitive hematopoietic stem and progenitor cells, and in the functions of some mature cells. More than 20 different molecules of HGF have been identified. Among them, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been demostrated to be effective in reducing the incidence of febrile neutropenia when administered inmediately after chemotherapy and as supportive therapy in patients undergoing bone marrow transplantation. Chemotherapy used for treatment of cancer often causes neutropenia, which may be profound, requiring hospitalization, and leading to potentially fatal infection. The uses of the recombinant human hematopoietic colony-stimulating factors G-CSF and GM-CSF for treatment and prophylaxis of chemotherapy-induced febrile neutropenia will be reviewed here.

Accuracy of malaria diagnosis by microscopy, rapid diagnostic test, and PCR methods and evidence of antimalarial overprescription in non-severe febrile patients in two Tanzanian hospitals.

PubMed

Nicastri, Emanuele; Bevilacqua, Nazario; Sañé Schepisi, Monica; Paglia, Maria G; Meschi, Silvia; Ame, Shaali M; Mohamed, Jape A; Mangi, Sabina; Fumakule, Robert; Di Caro, Antonino; Capobianchi, Maria R; Kitua, Andrew; Molteni, Fabrizio; Racalbuto, Vincenzo; Ippolito, Giuseppe

2009-05-01

The study was aimed to evaluate the malaria over/underdiagnosis and over/underprescription of antimalarial drugs. Between February and March 2007 blood samples were collected from 336 non-severe febrile outpatients attended in two peripheral Tanzanian hospitals. Microscopy and a rapid diagnostic test (RDT) were done locally and the accuracy evaluated by qualitative polymerase chain reaction (PCR) for Plasmodium spp. The testing was performed at National Institute for Infectious Diseases Lazzaro Spallanzani (INMI), Rome, Italy. As a result of PCR, we identified 26 malaria cases out of 336 (7.7%) patients. Microscopy and RDT accuracies were 93.5% and 97.6%, respectively. Overprescription and underdiagnosis rates were 29.3% and 30.8%, respectively. On-field training, clinical management of febrile illness, and malaria microscopy in remote settings should be considered.

Prevalence of malaria, typhoid, toxoplasmosis and rubella among febrile children in Cameroon.

PubMed

Achonduh-Atijegbe, Olivia A; Mfuh, Kenji O; Mbange, Aristid H E; Chedjou, Jean P; Taylor, Diane W; Nerurkar, Vivek R; Mbacham, Wilfred F; Leke, Rose

2016-11-08

The current roll-out of rapid diagnostic tests (RDTs) in many endemic countries has resulted in the reporting of fewer cases of malaria-attributed illnesses. However, lack of knowledge of the prevalence of other febrile illnesses and affordable diagnostic tests means that febrile patients are not managed optimally. This study assessed the prevalence of commonly treatable or preventable febrile illnesses in children between 6 months and 15 years using rapid diagnostic tests at the point-of-care. Febrile children were enrolled between February-April 2014 at a health facility after obtaining informed consent from parent. Eligible participants were aged 6 months-15 years with a history of fever in the last 24 h or axillary temperature ≥38 °C at consultation. All participants were tested using RDTs for malaria, typhoid, toxoplasmosis and rubella. Malaria parasites were further identified by microscopy and PCR. Clinical and household characteristics were recorded and association with pathogens determined. Of the 315 children enrolled, the mean age was 5.8 ± 3.8 years. Stomach pain (41.2 %) was the most reported symptom. Prior to attending the health facility, 70.8 % had taken antipyretics, 27.9 % antimalarials, 11.4 % antibiotics and 13.3 % antifungal drugs. Among 315 children with fever, based on RDTs, 56.8 % were infected with malaria, 4.4 % with typhoid, 3.2 % with acute toxoplasmosis, and 1.3 % with rubella (all positive for rubella were in the same family and not vaccinated). All non-malarial infections were co-infections and approximately 30 % of the fever cases went un-diagnosed. Malaria prevalence by microscopy and PCR was 43.4 and 70.2 % respectively. The sensitivity and specificity of RDTs for the diagnosis of malaria were 75.98 and 100 % respectively, with 0.73 measurement agreement between RDTs and microscopy while that of RDT and PCR were 81 and 100 % respectively with a K value of 0.72. The use of Insecticide Treated Bednets was 44 %. There was a significant association between ITN non-usage and malaria (p = 0. 029) as well as drinking water and presence of typhoid (p = 0.047). No association was observed between type of housing and malaria, or toxoplasmosis and raising cats. Though malaria still remains the major cause of fever in children, using RDTs for other treatable febrile illnesses like typhoid and toxoplasmosis could facilitate the optimal management of febrile illnesses in children especially when these occur as co-infections with malaria.

"... As we forgive those who trespass against us...": theological reflections on sin and guilt in the hospital environment.

PubMed

Schmidt, Kurt W

2005-08-01

In general parlance the term sin has lost its existential meaning. Originally a Jewish-Christian term within a purely religious context, referring to a wrongdoing with regard to God, sin has slowly become reduced to guilt in the course of the secularization process. Guilt refers to a wrongdoing, especially with regard to fellow human beings. It also refers to errors of judgement with what can be tragic consequences. These errors can occur whenever human beings are called upon to act, including the hospital environment. A Christian hospital has to address the issue of how to deal not only with guilt-ridden misdemeanors, but also with wrongdoing unto God, which overshadows every instance of guilt-ridden human behavior. Here, as in every parish, the Church Service is the place to acknowledge sin, confess sin, and forgive sin, beyond the boundaries of the parish itself.

Sin1, a Mutation Affecting Female Fertility in Arabidopsis, Interacts with Mod1, Its Recessive Modifier

PubMed Central

Lang, J. D.; Ray, S.; Ray, A.

1994-01-01

In Arabidopsis thaliana, a mutation in the SIN1 gene causes aberrant ovule development and female-specific sterility. The effect of the sin1 mutation is polymorphic and pleiotropic in different genetic backgrounds. The polymorphism concerns morphology of the mutant ovules. The pleiotropism involves internodal distance and inflorescence initiation time. The particular ovule phenotype and the length of internodes are dependent on an interaction of sin1 with a second recessive gene, which we term mod1. The recessive mod1 allele in a homozygous sin1 mutant plant reduces internode length and ovule integument size. The mutation sin1, but not mod1, has a demonstrable effect on ovule morphology when acting idependently. In our crosses mod1 was inseparably linked to the well known mutation erecta that is known to cause a reduction in internode and pedicel lengths. PMID:7982564

THE POSTERIOR DISTRIBUTION OF sin(i) VALUES FOR EXOPLANETS WITH M{sub T} sin(i) DETERMINED FROM RADIAL VELOCITY DATA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, Shirley; Turner, Edwin L., E-mail: cwho@lbl.gov

2011-09-20

Radial velocity (RV) observations of an exoplanet system giving a value of M{sub T} sin(i) condition (i.e., give information about) not only the planet's true mass M{sub T} but also the value of sin(i) for that system (where i is the orbital inclination angle). Thus, the value of sin(i) for a system with any particular observed value of M{sub T} sin(i) cannot be assumed to be drawn randomly from a distribution corresponding to an isotropic i distribution, i.e., the presumptive prior distribution. Rather, the posterior distribution from which it is drawn depends on the intrinsic distribution of M{sub T} formore » the exoplanet population being studied. We give a simple Bayesian derivation of this relationship and apply it to several 'toy models' for the intrinsic distribution of M{sub T} , on which we have significant information from available RV data in some mass ranges but little or none in others. The results show that the effect can be an important one. For example, even for simple power-law distributions of M{sub T} , the median value of sin(i) in an observed RV sample can vary between 0.860 and 0.023 (as compared to the 0.866 value for an isotropic i distribution) for indices of the power law in the range between -2 and +1, respectively. Over the same range of indices, the 95% confidence interval on M{sub T} varies from 1.0001-2.405 ({alpha} = -2) to 1.13-94.34 ({alpha} = +2) times larger than M{sub T} sin(i) due to sin(i) uncertainty alone. More complex, but still simple and plausible, distributions of M{sub T} yield more complicated and somewhat unintuitive posterior sin(i) distributions. In particular, if the M{sub T} distribution contains any characteristic mass scale M{sub c} , the posterior sin(i) distribution will depend on the ratio of M{sub T} sin(i) to M{sub c} , often in a non-trivial way. Our qualitative conclusion is that RV studies of exoplanets, both individual objects and statistical samples, should regard the sin(i) factor as more than a 'numerical constant of order unity' with simple and well-understood statistical properties. We argue that reports of M{sub T} sin(i) determinations should be accompanied by a statement of the corresponding confidence bounds on M{sub T} at, say, the 95% level based on an explicitly stated assumed form of the true M{sub T} distribution in order to reflect more accurately the mass uncertainties associated with RV studies.« less

TaC-coated graphite prepared via a wet ceramic process: Application to CVD susceptors for epitaxial growth of wide-bandgap semiconductors

NASA Astrophysics Data System (ADS)

Nakamura, Daisuke; Kimura, Taishi; Narita, Tetsuo; Suzumura, Akitoshi; Kimoto, Tsunenobu; Nakashima, Kenji

2017-11-01

A novel sintered tantalum carbide coating (SinTaC) prepared via a wet ceramic process is proposed as an approach to reducing the production cost and improving the crystal quality of bulk-grown crystals and epitaxially grown films of wide-bandgap semiconductors. Here, we verify the applicability of the SinTaC components as susceptors for chemical vapor deposition (CVD)-SiC and metal-organic chemical vapor deposition (MOCVD)-GaN epitaxial growth in terms of impurity incorporation from the SinTaC layers and also clarify the surface-roughness controllability of SinTaC layers and its advantage in CVD applications. The residual impurity elements in the SinTaC layers were confirmed to not severely incorporate into the CVD-SiC and MOCVD-GaN epilayers grown using the SinTaC susceptors. The quality of the epilayers was also confirmed to be equivalent to that of epilayers grown using conventional susceptors. Furthermore, the surface roughness of the SinTaC components was controllable over a wide range of average roughness (0.4 ≤ Ra ≤ 5 μm) and maximum height roughness (3 ≤ Rz ≤ 36 μm) through simple additional surface treatment procedures, and the surface-roughened SinTaC susceptor fabricated using these procedures was predicted to effectively reduce thermal stress on epi-wafers. These results confirm that SinTaC susceptors are applicable to epitaxial growth processes and are advantageous over conventional susceptor materials for reducing the epi-cost and improving the quality of epi-wafers.

48 CFR 538.7001 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... used in this subpart, means Schedule 70 information technology contracts, and Consolidated Products and Services Schedule contracts containing information technology SINs. The Consolidated Products and Services... Purchasing. No other Schedules, or SINs, containing information technology outside of Schedule 70 SINs, and...

48 CFR 538.7001 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... used in this subpart, means Schedule 70 information technology contracts, and Consolidated Products and Services Schedule contracts containing information technology SINs. The Consolidated Products and Services... Purchasing. No other Schedules, or SINs, containing information technology outside of Schedule 70 SINs, and...

48 CFR 538.7001 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... used in this subpart, means Schedule 70 information technology contracts, and Consolidated Products and Services Schedule contracts containing information technology SINs. The Consolidated Products and Services... Purchasing. No other Schedules, or SINs, containing information technology outside of Schedule 70 SINs, and...

48 CFR 538.7001 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... used in this subpart, means Schedule 70 information technology contracts, and Consolidated Products and Services Schedule contracts containing information technology SINs. The Consolidated Products and Services... Purchasing. No other Schedules, or SINs, containing information technology outside of Schedule 70 SINs, and...

48 CFR 538.7001 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... used in this subpart, means Schedule 70 information technology contracts, and Consolidated Products and Services Schedule contracts containing information technology SINs. The Consolidated Products and Services... Purchasing. No other Schedules, or SINs, containing information technology outside of Schedule 70 SINs, and...

Investigation of silicon surface passivation by silicon nitride film deposition

NASA Technical Reports Server (NTRS)

Olsen, L. C.

1984-01-01

The use of Sin sub x grown by plasma enhanced chemical vapor deposition (PECVO) for passivating silicon surfaces was studied. The application of PECVO SiN sub x films for passivations of silicon N+/P or P+/N solar cells is of particular interest. This program has involved the following areas of investigation: (1) Establishment of PECVO system and development of procedures for growth of SiN sub x; (2) Optical characterization of SiN sub x films; (3) Characterization of the SiN sub x/Si interface; (4) Surface recombination velocity deduced from photoresponse; (5) Current-Voltage analyses of silicon N+/P cells; and (6) Gated diode device studies.

The Fate of Primary Nonrefluxing Megaureter: A Prospective Outcome Analysis of the Rate of Urinary Tract Infections, Surgical Indications and Time to Resolution.

PubMed

Braga, Luis H; D'Cruz, Jennifer; Rickard, Mandy; Jegatheeswaran, Kizanee; Lorenzo, Armando J

2016-04-01

We examined data on a cohort of patients with primary nonrefluxing megaureter to determine risk factors for febrile urinary tract infection, indications for surgery and time to resolution. The records of patients younger than 24 months with primary nonrefluxing megaureter were prospectively captured from 2008 to 2015. Six a priori defined variables were studied, including gender, circumcision status, hydronephrosis SFU (Society for Fetal Urology) grade (low--1 and 2 vs high--3 and 4), continuous antibiotic prophylaxis use, ureteral dilatation (greater than 11 mm) and tortuosity. Univariate analyses and Cox hazard regression were done for febrile urinary tract infection risk factors. Resolution trends were analyzed using Kaplan-Meier curves. Mean ± SD age at the first clinic visit was 3.7 ± 4 months and mean followup was 26.3 ± 16.6 months. Of 80 patients with primary megaureter 66 (83%) had high grade hydronephrosis, 72 (90%) were male, 21 (26%) were circumcised and 40 (50%) had ureteral dilatation greater than 11 mm at baseline. Overall continuous antibiotic prophylaxis was prescribed to 34 patients (43%) and febrile urinary tract developed infection in 27 (34%) at a mean age of 5.8 months (median 3, range 1 to 24). Cox regression identified uncircumcised male gender (HR 3.4, 95% CI 1.1-10.7, p = 0.04) and lack of continuous antibiotic prophylaxis (HR 4.1, 95% CI 1.3-12.7, p = 0.01) as independent risk factors for febrile urinary tract infection. The 19 surgical patients (24%) had a larger mean ureteral diameter immediately preoperatively than those who did not require surgery (17 ± 5 vs 12 ± 4 mm, p <0.01). Kaplan-Meier curves showed that 85% of primary nonrefluxing megaureters that did not require surgery resolved in a median of 17 months. Febrile urinary tract infection developed in 34% of patients with primary nonrefluxing megaureter within the first 6 months of life. Circumcision and continuous antibiotic prophylaxis significantly decreased febrile urinary tract infection rates in those infants. Ureteral diameter 17 mm or greater was significantly associated with a higher rate of surgical intervention. Overall 76% of megaureters resolved during a median followup of 19 months. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Approximation properties of Fejér- and de la Valleé-Poussin-type means for partial sums of a special series in the system \\{\\sin x\\sin kx\\}_{k=1}^\\infty

NASA Astrophysics Data System (ADS)

Sharapudinov, I. I.

2015-04-01

This paper is concerned with series of the form \\displaystyle Φ(θ)=A_Φ(θ)+\\sinθ\\sumk=1^∞\\varphi_k\\sin kθ, where Φ(θ) is an even 2π-periodic function with finite values Φ(0) and Φ(π), \\displaystyle A_Φ(θ)=\\frac{Φ(0)+Φ(π)}{2}+\\frac{Φ(0)-Φ(π)}{2}\\cosθ,\\qquad\\varphi(θ)=Φ(θ)-A_Φ(θ), \\displaystyle \\varphi_k=\\frac{2}π\\int_0^π\\varphi(t)\\frac{\\sin kt}{\\sin t} dt. Series of this type appear as a particular case of more general special series in ultraspherical Jacobi polynomials, which were first introduced and studied by the author. Partial sums of the form \\Pi_n(Φ)=\\Pi_n(Φ,θ)=A_Φ(θ)+\\sinθ\\sumk=1n-1\\varphi_k\\sin kθ are shown to have a number of important properties, which give them an advantage over trigonometric Fourier sums of the form S_n(Φ,θ)=\\frac{a_0}{2}+\\sumk=1^na_k\\cos kθ. Approximation properties of Fejér- and de la Valleé-Poussin-type means for the partial sums \\Pi_n(Φ,θ) are studied. Bibliography: 7 titles.

Dma1-dependent degradation of SIN proteins during meiosis in Schizosaccharomyces pombe.

PubMed

Krapp, Andrea; Simanis, Viesturs

2014-07-15

The Schizosaccharomyces pombe septation initiation network (SIN) is required for cytokinesis during vegetative growth and for spore formation during meiosis. Regulation of the SIN during mitosis has been studied extensively, but less is known about its meiotic regulation. Here, we show that several aspects of SIN regulation differ between mitosis and meiosis. First, the presence of GTP-bound Spg1p is not the main determinant of the timing of Cdc7p and Sid1p association with the spindle pole body (SPB) during meiosis. Second, the localisation dependencies of SIN proteins differ from those in mitotic cells, suggesting a modified functional organisation of the SIN during meiosis. Third, there is stage-specific degradation of SIN components in meiosis; Byr4p is degraded after meiosis I, whereas the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second meiotic division and depends upon the ubiquitin ligase Dma1p. Finally, Dma1p-dependent degradation is not restricted to the SIN, as we show that Dma1p is needed for the degradation of Mcp6p (also known as Hrs1p) during meiosis I. Taken together, these data suggest that stage-specific targeted proteolysis plays an important role in regulating meiotic progression. © 2014. Published by The Company of Biologists Ltd.

Influence of the direct NO-donor SIN-1 on the interaction between platelets and stainless steel stents under dynamic conditions.

PubMed

Jung, F; Mrowietz, C; Seyfert, U T; Grewe, R; Franke, R P

2003-01-01

It was investigated whether the NO-donor SIN-1, the active metabolite of molsidomine, influenced the activation of platelets, the formation of circulating platelet aggregates, the spontaneous aggregation of platelets and the activation of the clotting system triggered by a body foreign surface in an in vitro closed-loop perfusion model. With human platelet-rich plasma at micromolar concentrations SIN-1 exerted pronounced effects on the interaction between platelets and an exogenous surface. In the absence of SIN-1, the number of circulating single platelets decreased significantly, which could be due either to the formation of circulating platelet aggregates or to the adhesion of platelets to the stent. Both these processes were blocked by the addition of SIN-1. Moreover, the platelets exhibited hyperaggregability in the absence of SIN-1 whereas the NO-donor was able to completely inhibit spontaneous platelet aggregation. Similar results were obtained in flow cytometry experiments. Without SIN-1, high platelet surface densities of both the GPIb/IX and GPIIb/IIIa receptors were observed. In addition, the density of the fibrinogen receptor increased significantly with the number of perfusion cycles. SIN-1 was able to suppress the augmented GPIIb/IIIa receptor expression significantly. Molsidomine seemed to have the potential to reduce the incidence of thrombotic processes triggered by the exogenous surface of the stent.

Protective Effects of Sinomenine on CFA-Induced Inflammatory Pain in Rats.

PubMed

Yuan, Yan; Zhang, Yongjun; He, Xiaofeng; Fan, Shengdeng

2018-04-05

BACKGROUND The purpose of this study was to investigate the effects of sinomenine (SIN) on CFA-induced inflammatory pain in rats, and to explore the underlying molecular mechanisms. MATERIAL AND METHODS To determine the potential influences of SIN in the pathogenesis of inflammatory pain, an inflammatory pain (IP) mouse model was established and rats were treated with SIN (30 mg/kg). Behavioral tests were used to assess the MWT and TWL of the rats. ELISA assay was used to detect the level of inflammation cytokines. Western blotting and qRT-PCR were carried out to measure the related protein and mRNA expression level, respectively. RESULTS We found that the MWT and TWL of the CFA-treated rats were markedly lower than that of the control rats, and they were significantly increased by SIN administration. The results suggest that IP rats had higher levels of TNF-α, IL-1β and IL-6 compared with the control rats. SIN administration decreased the levels of TNF-α, IL-1β, and IL-6. In addition, we found that p-p65 and p-p38 expression notably decreased after SIN treatment in IP rats. Moreover, the results showed that SIN inhibited Cox-2 and PGE2 expression in IP rats. CONCLUSIONS The data indicate that SIN had a protective role in inflammatory pain through repressing inflammatory mediators via preventing the p38MAPK-NF-κB pathway.

Central line-associated bloodstream infections in adult hematology patients with febrile neutropenia: an evaluation of surveillance definitions using differential time to blood culture positivity.

PubMed

Freeman, Joshua T; Elinder-Camburn, Anna; McClymont, Catherine; Anderson, Deverick J; Bilkey, Mary; Williamson, Deborah A; Berkahn, Leanne; Roberts, Sally A

2013-01-01

We used differential time to positivity between central and peripheral blood cultures to evaluate the positive predictive value (PPV) of the National Healthcare Safety Network central line-associated bloodstream infection (CLABSI) surveillance definition among hematology patients with febrile neutropenia. The PPV was 27.7%, which suggests that, when the definition is applied to this population, CLABSI rates will be substantially overestimated.

The Characterization and Treatment of Aggressive Breast Cancer

DTIC Science & Technology

2005-05-01

of a cycle for over 7 days, the carboplatin dose will be decreased by 25% for subsequent cycles. For a second episode of febrile neutropenia , G-CSF...should be given with the next cycle. For an episode of febrile neutropenia despite dose reduction and G-CSF, protocol treatment should be discontinued... neutropenia despite a dose reduction in the previous course. G-CSF may also be used as clinically indicated for neutropenic infection. 4.2.4 The use of

Gene Expression Analysis of Circulating Hormone Refractory Prostate Cancer Micrometastases

DTIC Science & Technology

2008-01-01

Toxicity Grade 3 or 4 neutropenia occurred in 54% and 63% of patients treated with second-line ixabepilone and MP, respectively (Table 3). Febrile ... Neutropenia 22 (54) 10 (33) 26 (63) 10 (63) Febrile neutropenia 2 (5)* 2 (7) 4 (10) — Thrombocytopenia 3 (7) 3 (10) 1 (2) 1 (6) * 1 patient died of...independently predicted improved survival. The most common grade 3/4 toxicity associated with second-line treatment was neutropenia (54% of ixabe- pilone

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with febrile urinary tract infection.

PubMed

Okamoto, Takayuki; Sato, Yasuyuki; Yamazaki, Takeshi; Hayashi, Asako

2014-04-01

Common pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) are viruses, such as influenza virus. However, bacteria are rare pathogens for MERS. We report the first patient with MERS associated with febrile urinary tract infection. A 16-year-old lupus patient was admitted to our hospital. She had fever, headache, vomiting, and right back pain. Urinary analysis showed leukocyturia, and urinary culture identified Klebsiella pneumoniae. Cerebrospinal fluid examination and brain single-photon emission computed tomography showed no abnormalities. Therefore, she was diagnosed with febrile urinary tract infection. For further examinations, 99mTc-dimercaptosuccinic acid renal scintigraphy showed right cortical defects, and a voiding cystourethrogram demonstrated right vesicoureteral reflux (grade II). Therefore, she was diagnosed with right pyelonephritis. Although treatment with antibiotics administered intravenously improved the fever, laboratory findings, and right back pain, she had prolonged headaches, nausea, and vomiting. T2-weighted, diffusion-weighted, and fluid attenuated inversion recovery images in brain magnetic resonance imaging showed high intensity lesions in the splenium of the corpus callosum, which completely disappeared 1 week later. These results were compatible with MERS. To the best of our knowledge, our patient is the first patient who showed clinical features of MERS associated with febrile urinary tract infection. In patients with pyelonephritis and an atypical clinical course, such as prolonged headache, nausea, vomiting, and neurological disorders, the possibility of MERS should be considered.

Accuracy of early DMSA scan for VUR in young children with febrile UTI.

PubMed

Zhang, Xin; Xu, Hong; Zhou, Lijun; Cao, Qi; Shen, Qian; Sun, Li; Fang, Xiaoyan; Guo, Wei; Zhai, Yihui; Rao, Jia; Pa, Mier; Zhao, Ruifang; Bi, Yunli

2014-01-01

To evaluate the accuracy of an acute (99m)Tc-dimercaptosuccinic acid (DMSA) scan in predicting dilating vesicoureteral reflux (VUR) among young children with a febrile urinary tract infection (UTI). The medical records of children (≤ 2 years of age), presenting with febrile UTI between January 2000 and December 2011, were retrospectively reviewed. A total of 523 children were included in this study, of whom 397 children (75.9%) had abnormal DMSA results and 178 children (34.0%) were identified as VUR on micturating cystourethrography (MCU). Among all the patients, the number of children with dilating VUR was 151 (28.9%). The rate of abnormal results on DMSA for the dilating VUR group was significantly higher than the rates for the non-VUR and low-grade VUR groups (P < .01). In the <6 months age group and ≥ 6 months age group, the sensitivities of DMSA in predicting dilating VUR were 96.15% and 100.0%, respectively, the negative predictive values were 97.26% and 100.0%, respectively, and the negative likelihood ratios were 0.0911 and 0.0000, respectively. For children ≤ 2 years of age with a febrile UTI, an acute DMSA scan is valuable in the exclusion of dilating VUR. The likelihood of the presence of dilating VUR on MCU is rather low when the result of DMSA is negative. DMSA should be conducted to assess the need for an MCU.

Ceftolozane/tazobactam for febrile UTI due to multidrug-resistant Pseudomonas aeruginosa in a patient with neurogenic bladder.

PubMed

Dinh, Aurélien; Davido, Benjamin; Calin, Ruxandra; Paquereau, Julie; Duran, Clara; Bouchand, Frédérique; Phé, Véronique; Chartier-Kastler, Emmanuel; Rottman, Martin; Salomon, Jérôme; Plésiat, Patrick; Potron, Anaïs

2017-01-01

Urinary tract infections (UTI) are a major public health problem among spinal cord injury (SCI) patients. They frequently involve multidrug-resistant (MDR) bacteria. Ceftolozane/tazobactam (C/T) is a novel antibiotic combination approved for complicated intra-abdominal and UTI caused by Gram-positive and Gram-negative organisms, including some MDR strains. Little is known about the use of this agent for complicated febrile UTI occurring among SCI patients with neurogenic bladder due to MDR Pseudomonas aeruginosa (PSA). We describe the case of a 35-year-old man with SCI due to multiple sclerosis, with a neurogenic bladder necessitating a bilateral nephrostomy and double J catheter, who developed a febrile UTI due to a MDR PSA, which was susceptible only to amikacin and colistin. Because of this MDR phenotype and the underlying kidney disease, a 1000 mg (1000 mg per 500 mg) dose of C/T was given as monotherapy every 8 h for 7 days, after 3 days of colistin and amikacin. Thanks to this treatment, the patient had a favorable outcome with no clinical signs of UTI or positive urine culture up to 1 month after diagnosis. C/T seems to be an effective and safe therapeutic option for febrile UTI due to MDR PSA in SCI patients with neurogenic bladder, even when administered in monotherapy for 10 days.

Outcome of severe infections in afebrile neutropenic cancer patients

PubMed Central

Mahkovic-Hergouth, Ksenija; Novakovic, Barbara Jezersek; Seruga, Bostjan

2016-01-01

Abstract Background In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia. Patients and methods We retrospectively analyzed all adult cancer patients with chemotherapy-induced neutropenia and severe infection, who were admitted to the Intensive Care Unit at our cancer center between 2000 and 2011. The outcome of interest was 30-day in-hospital mortality rate. Association between the febrile status and in-hospital mortality rate was evaluated by the Fisher’s exact test. Results We identified 69 episodes of severe neutropenic infections in 65 cancer patients. Among these, 9 (13%) episodes were afebrile. Patients with afebrile neutropenic infection presented with hypotension, severe fatigue with inappetence, shaking chills, altered mental state or cough and all of them eventually deteriorated to severe sepsis or septic shock. Overall 30-day in-hospital mortality rate was 55.1%. Patients with afebrile neutropenic infection had a trend for a higher 30-day in-hospital mortality rate as compared to patients with febrile neutropenic infection (78% vs. 52%, p = 0.17). Conclusions Afebrile cancer patients with chemotherapy-induced neutropenia and severe infections might have worse outcome as compared to cancer patients with febrile neutropenia. Patients should be informed that severe neutropenic infection without fever can occasionally occur during cancer treatment with chemotherapy. PMID:27904453

Effect of Influenza-Induced Fever on Human Bioimpedance Values

PubMed Central

Marini, Elisabetta; Buffa, Roberto; Contreras, Monica; Magris, Magda; Hidalgo, Glida; Sanchez, Wilmer; Ortiz, Vanessa; Urbaez, Maryluz; Cabras, Stefano; Blaser, Martin J.; Dominguez-Bello, Maria G.

2015-01-01

Background and Aims Bioelectrical impedance analysis (BIA) is a widely used technique to assess body composition and nutritional status. While bioelectrical values are affected by diverse variables, there has been little research on validation of BIA in acute illness, especially to understand prognostic significance. Here we report the use of BIA in acute febrile states induced by influenza. Methods Bioimpedance studies were conducted during an H1N1 influenza A outbreak in Venezuelan Amerindian villages from the Amazonas. Measurements were performed on 52 subjects between 1 and 40 years of age, and 7 children were re-examined after starting Oseltamivir treatment. Bioelectrical Impedance Vector Analysis (BIVA) and permutation tests were applied. Results For the entire sample, febrile individuals showed a tendency toward greater reactance (p=0.058) and phase angle (p=0.037) than afebrile individuals, while resistance and impedance were similar in the two groups. Individuals with repeated measurements showed significant differences in bioimpedance values associated with fever, including increased reactance (p<0.001) and phase angle (p=0.007), and decreased resistance (p=0.007) and impedance (p<0.001). Conclusions There are bioelectrical variations induced by influenza that can be related to dehydration, with lower extracellular to intracellular water ratio in febrile individuals, or a direct thermal effect. Caution is recommended when interpreting bioimpedance results in febrile states. PMID:25915945

Piperacillin-tazobactam vs. imipenem-cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia.

PubMed

Jing, Yu; Li, Jian; Yuan, Lei; Zhao, Xiaoli; Wang, Quanshun; Yu, Li; Zhou, Daobin; Huang, Wenrong

2016-03-01

This randomized, dual-center study compared the efficacy and safety of piperacillin-tazobactam (PTZ) and imipenem-cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of 10 patients in the PTZ group and one of eight patients in the IMP group needed to switch the empiric antibiotic (p = 0.025). Compared with PTZ, IMP had more gastrointestinal adverse events (p = 0.045). This study demonstrates that IMP had better efficacy than PTZ as an empiric antibiotic for febrile neutropenia in the HSCT setting, but with more gastrointestinal side reactions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dengue fever causing febrile neutropenia in children with acute lymphoblastic leukemia: an unknown entity.

PubMed

Ramzan, Mohammed; Yadav, Satya Prakash; Dinand, Veronique; Sachdeva, Anupam

2013-06-01

Dengue fever is endemic in many parts of the world but it has not been described as a cause of febrile neutropenia. We describe here clinical features, laboratory values and outcome in 10 children with acute lymphoblastic leukemia (ALL) and with dengue fever as a cause of febrile neutropenia. These data are compared to an age-matched control population of 22 children with proven dengue infection without ALL. Except for fever in all patients and plethoric face in one patient, typical symptoms of dengue such as abdominal pain, myalgias, and headaches, were absent. Mean duration of hospital stay was 6.3±2.0 days in ALL patients vs. 5.0±2.0 in controls (p=0.096). Median platelet count was 13,000/cmm (range 1000-28,000) in cases vs. 31,500 (range 13,000-150,000) in controls (p=0.018). Mean time for recovery for platelet was 6.0±1.3days in ALL patients vs. 2.5±0.9days in controls (p<0.001). All 10 patients survived. In endemic areas, high suspicion of dengue fever should be maintained in children with ALL and febrile neutropenia although typical symptoms may be lacking. Platelet recovery may be significantly delayed. Copyright © 2013 King Faisal Specialist Centre & Research Hospital. Published by Elsevier B.V. All rights reserved.

Significance of interleukin-6 (IL-6) and C-reactive protein (CRP) in children and young adults with febrile neutropenia during chemotherapy for cancer: a prospective study.

PubMed

Chaudhary, Narendra; Kosaraju, Kranthi; Bhat, Kamalakshi; Bairy, Indira; Borker, Anupama

2012-11-01

We evaluated the usefulness of interleukin-6 (IL-6) and C-reactive protein (CRP) at the onset of febrile neutropenia and 72 hours later, in identifying risk groups and assessing response to antibiotic therapy. All episodes of febrile neutropenia were divided in 3 study groups-microbiologically documented infection (MDI), clinically documented infection (CDI), and fever of unknown origin (FUO). Three outcome groups were defined as those responding to first-line antibiotics (R1), those responding to second-line antibiotics (R2), and those requiring antifungal therapy (RAF). Median values of IL-6 and CRP were compared between the groups. There were 57 episodes of febrile neutropenia among 26 patients younger than 25 years during 1 year of study period. On day 1, median IL-6 level was significantly lower in FUO group compared with CDI+MDI groups combined (P < 0.001). Rise in CRP on day 3 was highly significant to differentiate MDI group from other 2 groups (P < 0.001). The CRP also increased significantly on day 3 in RAF (P < 0.001) and R2 (P = 0.002) groups than in R1 group. Low level of IL-6 may help differentiate patients with FUO from those with documented infections. A rising CRP is indicative of serious infection.

A chimeric alphavirus replicon particle vaccine expressing the hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques from measles.

PubMed

Pan, Chien-Hsiung; Greer, Catherine E; Hauer, Debra; Legg, Harold S; Lee, Eun-Young; Bergen, M Jeff; Lau, Brandyn; Adams, Robert J; Polo, John M; Griffin, Diane E

2010-04-01

Measles remains a major cause of child mortality, in part due to an inability to vaccinate young infants with the current live attenuated virus vaccine (LAV). To explore new approaches to infant vaccination, chimeric Venezuelan equine encephalitis/Sindbis virus (VEE/SIN) replicon particles were used to express the hemagglutinin (H) and fusion (F) proteins of measles virus (MV). Juvenile rhesus macaques vaccinated intradermally with a single dose of VEE/SIN expressing H or H and F proteins (VEE/SIN-H or VEE/SIN-H+F, respectively) developed high titers of MV-specific neutralizing antibody and gamma-interferon (IFN-gamma)-producing T cells. Infant macaques vaccinated with two doses of VEE/SIN-H+F also developed neutralizing antibody and IFN-gamma-producing T cells. Control animals were vaccinated with LAV or with a formalin-inactivated measles vaccine (FIMV). Neutralizing antibody remained above the protective level for more than 1 year after vaccination with VEE/SIN-H, VEE/SIN-H+F, or LAV. When challenged with wild-type MV 12 to 17 months after vaccination, all vaccinated juvenile and infant monkeys vaccinated with VEE/SIN-H, VEE/SIN-H+F, and LAV were protected from rash and viremia, while FIMV-vaccinated monkeys were not. Antibody was boosted by challenge in all groups. T-cell responses to challenge were biphasic, with peaks at 7 to 25 days and at 90 to 110 days in all groups, except for the LAV group. Recrudescent T-cell activity coincided with the presence of MV RNA in peripheral blood mononuclear cells. We conclude that VEE/SIN expressing H or H and F induces durable immune responses that protect from measles and offers a promising new approach for measles vaccination. The viral and immunological factors associated with long-term control of MV replication require further investigation.

Transcriptional co-repressor SIN3A silencing rescues decline in memory consolidation during scopolamine-induced amnesia.

PubMed

Srivas, Sweta; Thakur, Mahendra K

2018-05-01

Epigenetic modifications through methylation of DNA and acetylation of histones modulate neuronal gene expression and regulate long-term memory. Earlier we demonstrated that scopolamine-induced decrease in memory consolidation is correlated with enhanced expression of hippocampal DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in mice. DNMT1 and HDAC2 act together by recruiting a co-repressor complex and deacetylating the chromatin. The catalytic activity of HDACs is mainly dependent on its incorporation into multiprotein co-repressor complexes, among which SIN3A-HDAC2 co-repressor is widely studied to regulate synaptic plasticity. However, the involvement of co-repressor complex in regulating memory loss or amnesia is unexplored. This study examines the role of co-repressor SIN3A in scopolamine-induced amnesia through epigenetic changes in the hippocampus. Scopolamine treatment remarkably enhanced hippocampal SIN3A expression in mice. To prevent such increase in SIN3A expression, we used hippocampal infusion of SIN3A-siRNA and assessed the effect of SIN3A silencing on scopolamine-induced amnesia. Silencing of SIN3A in amnesic mice reduced the binding of HDAC2 at neuronal immediate early genes (IEGs) promoter, but did not change the expression of HDAC2. Furthermore, it increased acetylation of H3K9 and H3K14 at neuronal IEGs (Arc, Egr1, Homer1 and Narp) promoter, prevented scopolamine-induced down-regulation of IEGs and improved consolidation of memory during novel object recognition task. These findings together suggest that SIN3A has a critical role in regulation of synaptic plasticity and might act as a potential therapeutic target to rescue memory decline during amnesia and other neuropsychiatric pathologies. © 2018 International Society for Neurochemistry.

PROTOCOL FOR REDUCING TIME TO ANTIBIOTICS IN FEBRILE NEONATES PRESENTING TO THE EMERGENCY DEPARTMENT: A QUALITY IMPROVEMENT INITIATIVE

PubMed Central

Boutin, A

2017-01-01

Abstract BACKGROUND: Febrile neonates are at high risk of morbidity and mortality from infectious causes. This risk further increases if antibiotics are not received in a timely manner. Current guidelines recommend early initiation (less than 1 hour) of antibiotics for patients with severe sepsis. Time-to-antibiotic administration (TAA) should also be targeted as a quality-of-care (QOC) measure for febrile neonates. A previous evaluation showed that most of these patients were not receiving antibiotics in the first hour at our emergency department (ED). OBJECTIVES: We evaluated whether a simple quality improvement protocol would improve the proportion of febrile neonates receiving antibiotics within 60 minutes of arrival to the ED. DESIGN/METHODS: This was a pre-post intervention study conducted in the ED of an academic pediatric tertiary care hospital with an annual volume of approximately 83,000 patients in 2014-2016. Participants were a random sample of all children younger than 28 days old visiting the ED for a febrile illness. The new protocol, which consisted for the nurses, after triage, to place the patients directly in the resuscitation room for immediate assessment by a physician, was implemented in February 2016. Previously, these children were triaged level 2 on the Canadian Triage and Acuity Scale (CTAS), flagged and placed in a regular examination room waiting for the physician assessment. With the new protocol, IV access, blood culture, urine analysis and culture were immediately obtained by the nurse in charge with the concomitant assessment by the attending physician. Forty charts prior to and 50 charts after protocol initiation were reviewed by an archivist using a standardized form between 2014-2015 and 2016, respectively. The primary outcome was TAA. This was defined as the time from initial ED registration to the beginning of antibiotics infusion. As a secondary outcome, all cases were reviewed individually to determine barriers to rapid antibiotic administration (day, evening, or night shifts, other treatments or investigations, number of attempts for intravenous access) and to elicit new quality improvement strategies. RESULTS: During the study periods a total of 178 (pre) and 135 (post) patients fulfilled the inclusion criteria. Among the random samples, 6/50 (12%) of patients received their antibiotics within 60 minutes in the post-intervention period compared to 0/40 (0%) in the pre-implementation period (difference 12%; 95 CI: 1-24%). Within 90 minutes, the proportion improved from 1/40 (2.5%) to 29/50 (58%) (difference 56%; 95 CI: 38-68%). Median TAA in febrile neonates decreased from 182 minutes (interquartile range, 147-219 minutes) in the pre-implementation period to 85 minutes (interquartile range, 73-115 minutes) in the post-implementation period. The main obstacle to the goal of 60 minutes for TAA was the difficulty to get IV access as well as antibiotic availability. CONCLUSION: In this study, a new protocol mandating the immediate transfer of febrile neonate from triage to the resuscitation room improved proportion of febrile neonates receiving antibiotics in less than 60 minutes in our ED. Our results suggest that simple interventions can reduce TAA in a selected group of patients presenting to the ED.

Integrated Positioning for Coal Mining Machinery in Enclosed Underground Mine Based on SINS/WSN

PubMed Central

Hui, Jing; Wu, Lei; Yan, Wenxu; Zhou, Lijuan

2014-01-01

To realize dynamic positioning of the shearer, a new method based on SINS/WSN is studied in this paper. Firstly, the shearer movement model is built and running regularity of the shearer in coal mining face has been mastered. Secondly, as external calibration of SINS using GPS is infeasible in enclosed underground mine, WSN positioning strategy is proposed to eliminate accumulative error produced by SINS; then the corresponding coupling model is established. Finally, positioning performance is analyzed by simulation and experiment. Results show that attitude angle and position of the shearer can be real-timely tracked by integrated positioning strategy based on SINS/WSN, and positioning precision meet the demand of actual working condition. PMID:24574891

The sin in the aetiological concept of Johann Christian August Heinroth (1773-1843). Part 1: Between theology and psychiatry. Heinroth's concepts of 'whose being', 'freedom', 'reason' and 'disturbance of the soul'.

PubMed

Steinberg, Holger

2004-09-01

Throughout his work Johann Christian August Heinroth regarded sin to be the cause of mental illness. The present two-part paper investigates what exactly Heinroth understood by sin. Based on a thorough analysis of his own texts, this study shows that on the one hand Heinroth referred to sin in a Christian-Protestant sense. On the other, however, a moral-ethical code of conduct was also involved. Thus, Heinroth did not regard sin as a singular event, but rather as a life conducted in a wrong way for years or even decades, by which he meant a steady striving towards earthly, bodily satisfaction.

Dengue and Chikungunya fever among viral diseases in outpatient febrile children in Kilosa district hospital, Tanzania.

PubMed

Chipwaza, Beatrice; Mugasa, Joseph P; Selemani, Majige; Amuri, Mbaraka; Mosha, Fausta; Ngatunga, Steve D; Gwakisa, Paul S

2014-11-01

Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria. A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2-13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used. A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35-3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus. Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended.

Choice of urine collection methods for the diagnosis of urinary tract infection in young, febrile infants.

PubMed

Schroeder, Alan R; Newman, Thomas B; Wasserman, Richard C; Finch, Stacia A; Pantell, Robert H

2005-10-01

The optimal method of urine collection in febrile infants is debatable; catheterization, considered more accurate, is technically difficult and invasive. To determine predictors of urethral catheterization in febrile infants and to compare bag and catheterized urine test performance characteristics. Prospective analysis of infants enrolled in the Pediatric Research in Office Settings' Febrile Infant Study. A total of 219 practices from within the Pediatric Research in Office Settings' network, including 44 states, the District of Columbia, and Puerto Rico. A total of 3066 infants aged 0 to 3 months with temperatures of 38 degrees C or higher. We calculated adjusted odds ratios for predictors of catheterization. Diagnostic test characteristics were compared between bag and catheterization. Urinary tract infection was defined as pure growth of 100 000 CFU/mL or more (bag) and 20 000 CFU/mL or more (catheterization). Seventy percent of urine samples were obtained by catheterization. Predictors of catheterization included female sex, practitioner older than 40 years, Medicaid, Hispanic ethnicity, nighttime evaluation, and severe dehydration. For leukocyte esterase levels, bag specimens demonstrated no difference in sensitivity but somewhat lower specificity (84% [bag] vs 94% [catheterization], P<.001) and a lower area under the receiver operating characteristic curve for white blood cells (0.71 [bag] vs 0.86 [catheterization], P = .01). Infection rates were similar in bag and catheterized specimens (8.5% vs 10.8%). Ambiguous cultures were more common in bag specimens (7.4% vs 2.7%, P<.001), but 21 catheterized specimens are needed to avoid each ambiguous bag result. Most practitioners obtain urine from febrile infants via catheterization, but choice of method is not related to the risk of urinary tract infection. Although both urine cultures and urinalyses are more accurate in catheterized specimens, the magnitude of difference is small but should be factored into clinical decision making.

Impact of a clinical decision model for febrile children at risk for serious bacterial infections at the emergency department: a randomized controlled trial.

PubMed

de Vos-Kerkhof, Evelien; Nijman, Ruud G; Vergouwe, Yvonne; Polinder, Suzanne; Steyerberg, Ewout W; van der Lei, Johan; Moll, Henriëtte A; Oostenbrink, Rianne

2015-01-01

To assess the impact of a clinical decision model for febrile children at risk for serious bacterial infections (SBI) attending the emergency department (ED). Randomized controlled trial with 439 febrile children, aged 1 month-16 years, attending the pediatric ED of a Dutch university hospital during 2010-2012. Febrile children were randomly assigned to the intervention (clinical decision model; n = 219) or the control group (usual care; n = 220). The clinical decision model included clinical symptoms, vital signs, and C-reactive protein and provided high/low-risks for "pneumonia" and "other SBI". Nurses were guided by the intervention to initiate additional tests for high-risk children. The clinical decision model was evaluated by 1) area-under-the-receiver-operating-characteristic-curve (AUC) to indicate discriminative ability and 2) feasibility, to measure nurses' compliance to model recommendations. Primary patient outcome was defined as correct SBI diagnoses. Secondary process outcomes were defined as length of stay; diagnostic tests; antibiotic treatment; hospital admission; revisits and medical costs. The decision model had good discriminative ability for both pneumonia (n = 33; AUC 0.83 (95% CI 0.75-0.90)) and other SBI (n = 22; AUC 0.81 (95% CI 0.72-0.90)). Compliance to model recommendations was high (86%). No differences in correct SBI determination were observed. Application of the clinical decision model resulted in less full-blood-counts (14% vs. 22%, p-value < 0.05) and more urine-dipstick testing (71% vs. 61%, p-value < 0.05). In contrast to our expectations no substantial impact on patient outcome was perceived. The clinical decision model preserved, however, good discriminatory ability to detect SBI, achieved good compliance among nurses and resulted in a more standardized diagnostic approach towards febrile children, with less full blood-counts and more rightfully urine-dipstick testing. Nederlands Trial Register NTR2381.

Impact of a Clinical Decision Model for Febrile Children at Risk for Serious Bacterial Infections at the Emergency Department: A Randomized Controlled Trial

PubMed Central

de Vos-Kerkhof, Evelien; Nijman, Ruud G.; Vergouwe, Yvonne; Polinder, Suzanne; Steyerberg, Ewout W.; van der Lei, Johan; Moll, Henriëtte A.; Oostenbrink, Rianne

2015-01-01

Objectives To assess the impact of a clinical decision model for febrile children at risk for serious bacterial infections (SBI) attending the emergency department (ED). Methods Randomized controlled trial with 439 febrile children, aged 1 month-16 years, attending the pediatric ED of a Dutch university hospital during 2010-2012. Febrile children were randomly assigned to the intervention (clinical decision model; n=219) or the control group (usual care; n=220). The clinical decision model included clinical symptoms, vital signs, and C-reactive protein and provided high/low-risks for “pneumonia” and “other SBI”. Nurses were guided by the intervention to initiate additional tests for high-risk children. The clinical decision model was evaluated by 1) area-under-the-receiver-operating-characteristic-curve (AUC) to indicate discriminative ability and 2) feasibility, to measure nurses’ compliance to model recommendations. Primary patient outcome was defined as correct SBI diagnoses. Secondary process outcomes were defined as length of stay; diagnostic tests; antibiotic treatment; hospital admission; revisits and medical costs. Results The decision model had good discriminative ability for both pneumonia (n=33; AUC 0.83 (95% CI 0.75-0.90)) and other SBI (n=22; AUC 0.81 (95% CI 0.72-0.90)). Compliance to model recommendations was high (86%). No differences in correct SBI determination were observed. Application of the clinical decision model resulted in less full-blood-counts (14% vs. 22%, p-value<0.05) and more urine-dipstick testing (71% vs. 61%, p-value<0.05). Conclusions In contrast to our expectations no substantial impact on patient outcome was perceived. The clinical decision model preserved, however, good discriminatory ability to detect SBI, achieved good compliance among nurses and resulted in a more standardized diagnostic approach towards febrile children, with less full blood-counts and more rightfully urine-dipstick testing. Trial Registration Nederlands Trial Register NTR2381 PMID:26024532

Clinician assessment for acute chest syndrome in febrile patients with sickle cell disease: is it accurate enough?

PubMed

Morris, C; Vichinsky, E; Styles, L

1999-07-01

To determine whether the use of empiric chest radiography (CXR) is of significant value in detecting clinically unsuspected acute chest syndrome (ACS) in febrile patients with sickle cell disease (SCD). Patients with SCD presenting to the emergency department and hematology clinic with temperature greater than or equal to 38 degrees C were prospectively evaluated using a physician-completed questionnaire. The questionnaire included inquiries into the patient's physical signs and symptoms and the physician's clinical impression for the presence of ACS. The questionnaire was completed before obtaining CXR results in all patients. Seventy-three patients with SCD with 96 febrile events were evaluated over a 1-year period. Twenty-four percent (23/96) of the patients had CXR evidence of ACS. On the basis of the questionnaire data, 61% (14/23) of ACS cases were not clinically suspected by the evaluating physician before obtaining CXR. Comparing the patients with and without ACS revealed that, with the exception of splinting (4/23 [17%] versus 0/73 [0%]), no symptom or physical examination finding helped to identify which patients had ACS. Fifty-seven percent of patients with ACS had completely normal findings on physical examination. The presentation of patients with clinically detected versus clinically unsuspected ACS also did not differ significantly. Length of hospitalization, oxygen use, and need for transfusion were the same in both the unsuspected and detected ACS groups. Overall physician sensitivity for predicting ACS was only 39%, and diagnostic accuracy did not improve significantly with increasing levels of pediatric training. ACS is common in patients with SCD who present with fever and was grossly underestimated by evaluating physicians. History and physical examination appear to be of little value in defining which febrile patients require CXR. In view of the mortality and morbidity associated with ACS, empiric CXR should be considered when evaluating a febrile patient with SCD.

Leptospirosis and Human Immunodeficiency Virus Co-Infection Among Febrile Inpatients in Northern Tanzania

PubMed Central

Biggs, Holly M.; Galloway, Renee L.; Bui, Duy M.; Morrissey, Annie B.; Maro, Venance P.

2013-01-01

Abstract Background Leptospirosis and human immunodeficiency virus (HIV) infection are prevalent in many areas, including northern Tanzania, yet little is known about their interaction. Methods We enrolled febrile inpatients at two hospitals in Moshi, Tanzania, over 1 year and performed HIV antibody testing and the microscopic agglutination test (MAT) for leptospirosis. Confirmed leptospirosis was defined as ≥four-fold rise in MAT titer between acute and convalescent serum samples, and probable leptospirosis was defined as any reciprocal MAT titer ≥800. Results Confirmed or probable leptospirosis was found in 70 (8.4%) of 831 participants with at least one serum sample tested. At total of 823 (99.0%) of 831 participants had HIV testing performed, and 203 (24.7%) were HIV infected. Among HIV-infected participants, 9 (4.4%) of 203 had confirmed or probable leptospirosis, whereas among HIV-uninfected participants 61 (9.8%) of 620 had leptospirosis. Leptospirosis was less prevalent among HIV-infected as compared to HIV-uninfected participants [odds ratio (OR) 0.43, p=0.019]. Among those with leptospirosis, HIV-infected patients more commonly presented with features of severe sepsis syndrome than HIV-uninfected patients, but differences were not statistically significant. Among HIV-infected patients, severe immunosuppression was not significantly different between those with and without leptospirosis (p=0.476). Among HIV-infected adolescents and adults, median CD4 percent and median CD4 count were higher among those with leptospirosis as compared to those with other etiologies of febrile illness, but differences in CD4 count did not reach statistical significance (p=0.015 and p=0.089, respectively). Conclusions Among febrile inpatients in northern Tanzania, leptospirosis was not more prevalent among HIV-infected patients. Although some indicators of leptospirosis severity were more common among HIV-infected patients, a statistically significant difference was not demonstrated. Among HIV-infected patients, those with leptospirosis were not more immunosuppressed relative to those with other etiologies of febrile illness. PMID:23663165

Evaluation of malnutrition as a predictor of adverse outcomes in febrile neutropenia associated with paediatric haematological malignancies.

PubMed

Chaudhuri, Jasodhara; Biswas, Tamoghna; Datta, Jyotishka; Sabui, Tapas Kumar; Chatterjee, Sukanta; Ray, Somosri; Raychaudhuri, Dibyendu; Mandal, Kalyanbrata; Chatterjee, Kaushani; Chakraborty, Swapna

2016-07-01

Malnutrition has been reported in the literature to be adversely associated with outcomes in paediatric malignancies. Our objective in this paper was to evaluate malnutrition as a potential predictor for adverse outcomes in febrile neutropenia associated with haematological malignancies. A prospective observational study was performed in a tertiary care teaching hospital of Kolkata, India. Forty-eight participants, suffering from haematological malignancy, were included. Participants were included if they experienced at least one episode of febrile neutropenia. For children aged <5 years, weight for height, height for age and weight for age were used as criteria for defining malnutrition, while body mass index for age was used in children ≥5 years. A total of 162 episodes of febrile neutropenia were studied. Thirty patients (30/48, 62.5%) included in the study had malnutrition. In bivariate analyses at patient level, there is a strong association between malnutrition and death (odds ratio (OR) 7.286, 95% confidence interval (CI) 0.838-63.345, one-tailed P = 0.044), and life-threatening complications show a moderate trend towards significance (OR 3.333, 95% CI 0.791-14.052, one-tailed P = 0.084). Survival functions were significantly different between malnourished and non-malnourished children (log rank test χ(2)  = 4.609, degree of freedom = 1, P = 0.032). Wasting was associated with life-threatening complications in children aged <5 years (OR 14, 95% CI 1.135-172.642, one-tailed P = 0.036). Logistic regression analyses at episode level revealed that phase of treatment and respiratory system involvement were significant predictors of death, while malnutrition was not. Malnutrition may be a potential predictor of mortality in febrile neutropenia. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Management of uncomplicated malaria in febrile under five-year-old children by community health workers in Madagascar: reliability of malaria rapid diagnostic tests

PubMed Central

2012-01-01

Background Early diagnosis, as well as prompt and effective treatment of uncomplicated malaria, are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria, reduce mortality and limit malaria transmission. The purpose of this study was to assess the performance of the malaria rapid diagnostic tests (RDTs) used by community health workers (CHWs) by comparing RDT results with two reference methods (microscopy and Polymerase Chain Reaction, PCR). Methods Eight CHWs in two districts, each with a different level of endemic malaria transmission, were trained to use RDTs in the management of febrile children under five years of age. RDTs were performed by CHWs in all febrile children who consulted for fever. In parallel, retrospective parasitological diagnoses were made by microscopy and PCR. The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs. The stability of the RDTs stored by CHWs was also evaluated. Results Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010, 89.5% were found to be positive for malaria parasites by PCR, 51.6% were positive by microscopy and 55.8% were positive by RDT. The performance accuracy of the RDTs used by CHWs in terms of sensitivity, specificity, positive and negative predictive values was greater than 85%. Concordance between microscopy and RDT, estimated by the Kappa value was 0.83 (95% CI: 0.75-0.91). RDTs stored by CHWs for 24 months were capable of detecting Plasmodium falciparum in blood at a level of 200 parasites/μl. Conclusion Introduction of easy-to-use diagnostic tools, such as RDTs, at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs. PMID:22443344

Management of uncomplicated malaria in febrile under five-year-old children by community health workers in Madagascar: reliability of malaria rapid diagnostic tests.

PubMed

Ratsimbasoa, Arsène; Ravony, Harintsoa; Vonimpaisomihanta, Jeanne-Aimée; Raherinjafy, Rogelin; Jahevitra, Martial; Rapelanoro, Rabenja; Rakotomanga, Jean De Dieu Marie; Malvy, Denis; Millet, Pascal; Ménard, Didier

2012-03-25

Early diagnosis, as well as prompt and effective treatment of uncomplicated malaria, are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria, reduce mortality and limit malaria transmission. The purpose of this study was to assess the performance of the malaria rapid diagnostic tests (RDTs) used by community health workers (CHWs) by comparing RDT results with two reference methods (microscopy and Polymerase Chain Reaction, PCR). Eight CHWs in two districts, each with a different level of endemic malaria transmission, were trained to use RDTs in the management of febrile children under five years of age. RDTs were performed by CHWs in all febrile children who consulted for fever. In parallel, retrospective parasitological diagnoses were made by microscopy and PCR. The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs. The stability of the RDTs stored by CHWs was also evaluated. Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010, 89.5% were found to be positive for malaria parasites by PCR, 51.6% were positive by microscopy and 55.8% were positive by RDT. The performance accuracy of the RDTs used by CHWs in terms of sensitivity, specificity, positive and negative predictive values was greater than 85%. Concordance between microscopy and RDT, estimated by the Kappa value was 0.83 (95% CI: 0.75-0.91). RDTs stored by CHWs for 24 months were capable of detecting Plasmodium falciparum in blood at a level of 200 parasites/μl. Introduction of easy-to-use diagnostic tools, such as RDTs, at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs.

Should Malaria Treatment Be Guided by a Point of Care Rapid Test? A Threshold Approach to Malaria Management in Rural Burkina Faso

PubMed Central

Bisoffi, Zeno; Tinto, Halidou; Sirima, Bienvenu Sodiomon; Gobbi, Federico; Angheben, Andrea; Buonfrate, Dora; Van den Ende, Jef

2013-01-01

Background In Burkina Faso, rapid diagnostic tests for malaria have been made recently available. Previously, malaria was managed clinically. This study aims at assessing which is the best management option of a febrile patient in a hyperendemic setting. Three alternatives are: treating presumptively, testing, or refraining from both test and treatment. The test threshold is the tradeoff between refraining and testing, the test-treatment threshold is the tradeoff between testing and treating. Only if the disease probability lies between the two should the test be used. Methods and Findings Data for this analysis was obtained from previous studies on malaria rapid tests, involving 5220 patients. The thresholds were calculated, based on disease risk, treatment risk and cost, test accuracy and cost. The thresholds were then matched against the disease probability. For a febrile child under 5 in the dry season, the pre-test probability of clinical malaria (3.2%), was just above the test/treatment threshold. In the rainy season, that probability was 63%, largely above the test/treatment threshold. For febrile children >5 years and adults in the dry season, the probability was 1.7%, below the test threshold, while in the rainy season it was higher (25.1%), and situated between the two thresholds (3% and 60.9%), only if costs were not considered. If they were, neither testing nor treating with artemisinin combination treatments (ACT) would be recommended. Conclusions A febrile child under 5 should be treated presumptively. In the dry season, the probability of clinical malaria in adults is so low, that neither testing nor treating with any regimen should be recommended. In the rainy season, if costs are considered, a febrile adult should not be tested, nor treated with ACT, but a possible alternative would be a presumptive treatment with amodiaquine plus sulfadoxine-pyrimethamine. If costs were not considered, testing would be recommended. PMID:23472129

Microcomputers and the Electrical Engineer.

DTIC Science & Technology

1984-07-01

B6 10*SIN(B4*B1I) 12 BII+B6 10*SIN(B4*812) 13 B12+B6 1O*SIN(B4*BI3) 14 B13+B6 10*SIN(B4*B14) 15 B14+B6 10*SIN(B4*BI5) 16 B15+B6 10*SIN(B4* Bl6 ) 17 B16 ...C15)),AND(D15,NOT(EI5 16 0 0 1 0 OR(AND( B16 ,NOT(C16)),AND(D16,NOT(E16 a17 0 0 0 1 OR(AND(B17,NOT(C17)),AND(D17,NOT(E17 18 0 0 0 0 OR(AND(B18,NOT(C18...NOT(E15)) 16 0 0 010 AND(AND( Bl6 ,NOT(Cl7)),AND(D16,NOT(E16)) 18 0) 0 0 0 AND(AND(B18,NOT(C18)),AND(D18,NOT(E18)) 19 Figure 3 I A IIBIJCIIDIIEII F I 1

Modification of silicon nitride surfaces with GOPES and APTES for antibody immobilization: computational and experimental studies

NASA Astrophysics Data System (ADS)

Dien To, Thien; Nguyen, Anh Tuan; Nhat Thanh Phan, Khoa; Thu Thi Truong, An; Doan, Tin Chanh Duc; Mau Dang, Chien

2015-12-01

Chemical modification of silicon nitride (SiN) surfaces by silanization has been widely studied especially with 3-(aminopropyl)triethoxysilane (APTES) and 3-(glycidyloxypropyl) dimethylethoxysilane (GOPES). However few reports performed the experimental and computational studies together. In this study, surface modification of SiN surfaces with GOPES and APTES covalently bound with glutaraldehyde (GTA) was investigated for antibody immobilization. The monoclonal anti-cytokeratin-FITC (MACF) antibody was immobilized on the modified SiN surfaces. The modified surfaces were characterized by water contact angle measurements, atomic force microscopy and fluorescence microscopy. The FITC-fluorescent label indicated the existence of MACF antibody on the SiN surfaces and the efficiency of the silanization reaction. Absorption of APTES and GOPES on the oxidized SiN surfaces was computationally modeled and calculated by Materials Studio software. The computational and experimental results showed that modification of the SiN surfaces with APTES and GTA was more effective than the modification with GOPES.

[Control levels of Sin3 histone deacetylase for spontaneous and UV-induced mutagenesis in yeasts Saccharomyces cerevisiae].

PubMed

Lebovka, I Iu; Kozhina, T N; Fedorova, I V; Peshekhonov, V T; Evstiukhina, T A; Chernenkov, A Iu; Korolev, V G

2014-01-01

SIN3 gene product operates as a repressor for a huge amount of genes in Saccharomyces cerevisiae. Sin3 protein with a mass of about 175 kDa is a member of the RPD3 protein complex with an assessed mass of greater than 2 million Da. It was previously shownthat RPD3 gene mutations influence recombination and repair processes in S. cerevisiae yeasts. We studied the impacts of the sin3 mutation on UV-light sensitivity and UV-induced mutagenesis in budding yeast cells. The deletion ofthe SIN3 gene causes weak UV-sensitivity of mutant budding cells as compared to the wild-type strain. These results show that the sin3 mutation decreases both spontaneous and UV-induced levels of levels. This fact is hypothetically related to themalfunction of ribonucleotide reductase activity regulation, which leads to a decrease in the dNTP pool and the inaccurate error-prone damage bypass postreplication repair pathway, which in turn provokes a reduction in the incidence of mutations.

Reversal of an Epigenetic Switch Governing Cell Chaining in Bacillus subtilis by Protein Instability

PubMed Central

Chai, Yunrong; Kolter, Roberto; Losick, Richard

2010-01-01

Bacillus subtilis forms long chains of cells during growth and biofilm formation. Cell separation is mediated by autolysins, whose genes are under the negative control of a heteromeric complex composed of the proteins SinR and SlrR. Formation of the SinR•SlrR complex is governed by a self-reinforcing, double-negative feedback loop in which SinR represses the gene for SlrR and SlrR, by forming the SinR•SlrR complex, titrates SinR and prevents it from repressing slrR. The loop is a bistable switch and exists in a SlrRLOW state in which autolysin genes are on, and a SlrRHIGH state in which autolysin genes are repressed by SinR•SlrR. Cells in the SlrRLOW state are driven into the SlrRHIGH state by SinI, an antirepressor that binds to and inhibits SinR. However, the mechanism by which cells in the SlrRHIGH state revert back to the SlrRLOW state is unknown. We report that SlrR is proteolytically unstable and present evidence that self-cleavage via a LexA-like autopeptidase and ClpC contribute to its degradation. Cells producing a self-cleavage-resistant mutant of SlrR exhibited more persistent chaining during growth and yielded biofilms with enhanced structural complexity. We propose that degradation of SlrR allows cells to switch from the SlrRHIGH to the SlrRLOW state. PMID:20923420

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2008-10-01

for > 3 platelet transfusion in 30 days • Gr 4 neutropenia • Febrile neutropenia • Attributable Gr > 3 non-hematologic toxicity (excluding infusion...0% No febrile neutropenia (no growth factor use) • Transaminitis (n=12 evaluable) Transient Gr 1 17% (no Gr > 1) Figure-1...therapies and 36% progressed on 1-4 lines of chemotherapy including docetaxel. No DLT’s have been seen. 2 pts experienced reversible Gr 3 neutropenia

48 CFR 538.7004 - Solicitation provisions and contract clauses.

Code of Federal Regulations, 2010 CFR

2010-10-01

...— (1) Schedule 70; (2) The Consolidated Schedule containing information technology SINs; and (3... Schedule containing information technology SINs; and (3) Schedule 84. (c) The contracting officer shall... information technology SINs; and (3) Schedule 84. (d) See 552.101-70 for authorized FAR deviations. [73 FR...

48 CFR 538.7004 - Solicitation provisions and contract clauses.

Code of Federal Regulations, 2011 CFR

2011-10-01

...— (1) Schedule 70; (2) The Consolidated Schedule containing information technology SINs; and (3... Schedule containing information technology SINs; and (3) Schedule 84. (c) The contracting officer shall... information technology SINs; and (3) Schedule 84. (d) See 552.101-70 for authorized FAR deviations. [73 FR...

Experimental evidence of trap level modulation in silicon nitride thin films by hydrogen annealing

NASA Astrophysics Data System (ADS)

Seki, Harumi; Kamimuta, Yuuichi; Mitani, Yuichiro

2018-06-01

The energy level of electron traps in silicon nitride (SiN x ) thin films was investigated by discharging current transient spectroscopy (DCTS). Results indicate that the trap level of the SiN x thin films becomes deeper with decreasing composition (N/Si) and shallower after hydrogen annealing. The dependence of the trap level on the SiN x composition and the modulation of the trap level by hydrogen annealing are possibly related to the change in the number of Si–H bonds in the SiN x thin films.

SIN3A mutations are rare in men with azoospermia.

PubMed

Miyamoto, T; Koh, E; Tsujimura, A; Miyagawa, Y; Minase, G; Ueda, Y; Namiki, M; Sengoku, K

2015-11-01

A loss of function of the murine Sin3A gene resulted in male infertility with Sertoli cell-only syndrome (SCOS) phenotype in mice. Here, we investigated the relevance of this gene to human male infertility with azoospermia caused by SCOS. Mutation analysis of SIN3A in the coding region was performed on 80 Japanese patients. However, no variants could be detected. This study suggests a lack of association of SIN3A gene sequence variants with azoospermia caused by SCOS in humans. © 2014 Blackwell Verlag GmbH.

The sin in the aetiological concept of Johann Christian August Heinroth (1773-1843): Part 2: Self-guilt as turning away from reason in the framework of Heinroth's concept of the interrelationships between body and soul.

PubMed

Steinberg, Holger

2004-12-01

Throughout his work Johann Christian August Heinroth regarded sin to be the cause of mental illness. The present two-part paper investigates what exactly Heinroth understood by sin. Based on a thorough analysis of his own texts, this study shows that on the one hand Heinroth referred to sin in a Christian-Protestant sense. On the other, however, a moral-ethical code of conduct was also involved. Thus, Heinroth did not regard sin as a singular event, but rather as a life conducted in a wrong way for years or even decades, by which he meant a steady striving towards earthly, bodily satisfaction.

Selective layer disordering in intersubband Al 0.028Ga 0.972 N/AlN superlattices with silicon nitride capping layer

DOE PAGES

Wierer, Jonathan J.; Allerman, Andrew A.; Skogen, Erik J.; ...

2015-06-01

We demonstrate the selective layer disordering in intersubband Al 0.028Ga 0.972 N/AlN superlattices using a silicon nitride (SiN x) capping layer. The (SiN x) capped superlattice exhibits suppressed layer disordering under high-temperature annealing. In addition, the rate of layer disordering is reduced with increased SiN x thickness. The layer disordering is caused by Si diffusion, and the SiN x layer inhibits vacancy formation at the crystal surface and ultimately, the movement of Al and Ga atoms across the heterointerfaces. In conclusion, patterning of the SiN x layer results in selective layer disordering, an attractive method to integrate active and passivemore » III–nitride-based intersubband devices.« less

What Is Happening at Spectral Type F5 in Hyades F Stars?

NASA Technical Reports Server (NTRS)

Boehm-Vitense, Erika; Robinson, Richard; Carpenter, Kenneth; Mena-Werth, Jose

2002-01-01

Aiming at a better understanding of the mechanisms heating the chromospheres, transition regions, and coronae of cool stars, we study ultraviolet, low-resolution Hubble Space Telescope/Space Telescope Imaging Spectrograph spectra of Hyades main-sequence F stars. We study the B-V dependence(s) of the chromospheric and transition layer emission line fluxes and their dependences on rotational velocities. We find that the transition layer emission line fluxes and also those of strong chromospheric lines decrease steeply between B-V = 0.42 and 0.45, i.e., at spectral type F5, for which the rotational velocities also decrease steeply. The magnitude of the line-flux decrease increases for lines of ions with increasing degree of ionization. This shows that the line-flux decrease is not due to a change in the surface filling factor but rather due to a change of the relative importance of different heating mechanisms. For early F stars with B-V < 0.42 we find for the transition layer emission lines increasing fluxes for increasing v sin i, indicating magnetohydrodynamic heating. The v sin i dependence is strongest for the high-ionization lines. On the other hand, the low chromospheric lines show no dependence on v sin i, indicating acoustic shock heating for these layers. This also contributes to the heating of the transition layers. The Mg II and Ca II lines show decreasing fluxes for increasing v sin i, as long as v sin i is less than approx. 40 km/s. The coronal X-ray emission also decreases for increasing v sin i, except for v sin i larger than approx. 100 km/s. We have at present no explanation for this behavior. For late F stars the chromospheric lines show v sin i dependences similar to those observed for early F stars, again indicating acoustic heating for these layers. We were unable to determine the v sin i dependence of the transition layer lines because of too few single star targets. The decrease of emission line fluxes at the spectral type F5, with steeply decreasing v sin i, indicates, however, a decreasing contribution of magnetohydrodynamic heating for the late F stars. The X-ray emission for the late F stars increases for increasing v sin i, indicating magnetohydrodynamic heating for the coronae of the late F stars, different from the early F stars.

High Prevalence of Intermediate Leptospira spp. DNA in Febrile Humans from Urban and Rural Ecuador.

PubMed

Chiriboga, Jorge; Barragan, Verónica; Arroyo, Gabriela; Sosa, Andrea; Birdsell, Dawn N; España, Karool; Mora, Ana; Espín, Emilia; Mejía, María Eugenia; Morales, Melba; Pinargote, Carmina; Gonzalez, Manuel; Hartskeerl, Rudy; Keim, Paul; Bretas, Gustavo; Eisenberg, Joseph N S; Trueba, Gabriel

2015-12-01

Leptospira spp., which comprise 3 clusters (pathogenic, saprophytic, and intermediate) that vary in pathogenicity, infect >1 million persons worldwide each year. The disease burden of the intermediate leptospires is unclear. To increase knowledge of this cluster, we used new molecular approaches to characterize Leptospira spp. in 464 samples from febrile patients in rural, semiurban, and urban communities in Ecuador; in 20 samples from nonfebrile persons in the rural community; and in 206 samples from animals in the semiurban community. We observed a higher percentage of leptospiral DNA-positive samples from febrile persons in rural (64%) versus urban (21%) and semiurban (25%) communities; no leptospires were detected in nonfebrile persons. The percentage of intermediate cluster strains in humans (96%) was higher than that of pathogenic cluster strains (4%); strains in animal samples belonged to intermediate (49%) and pathogenic (51%) clusters. Intermediate cluster strains may be causing a substantial amount of fever in coastal Ecuador.

High Prevalence of Intermediate Leptospira spp. DNA in Febrile Humans from Urban and Rural Ecuador

PubMed Central

Chiriboga, Jorge; Barragan, Verónica; Arroyo, Gabriela; Sosa, Andrea; Birdsell, Dawn N.; España, Karool; Mora, Ana; Espín, Emilia; Mejía, María Eugenia; Morales, Melba; Pinargote, Carmina; Gonzalez, Manuel; Hartskeerl, Rudy; Keim, Paul; Bretas, Gustavo; Eisenberg, Joseph N.S.

2015-01-01

Leptospira spp., which comprise 3 clusters (pathogenic, saprophytic, and intermediate) that vary in pathogenicity, infect >1 million persons worldwide each year. The disease burden of the intermediate leptospires is unclear. To increase knowledge of this cluster, we used new molecular approaches to characterize Leptospira spp. in 464 samples from febrile patients in rural, semiurban, and urban communities in Ecuador; in 20 samples from nonfebrile persons in the rural community; and in 206 samples from animals in the semiurban community. We observed a higher percentage of leptospiral DNA–positive samples from febrile persons in rural (64%) versus urban (21%) and semiurban (25%) communities; no leptospires were detected in nonfebrile persons. The percentage of intermediate cluster strains in humans (96%) was higher than that of pathogenic cluster strains (4%); strains in animal samples belonged to intermediate (49%) and pathogenic (51%) clusters. Intermediate cluster strains may be causing a substantial amount of fever in coastal Ecuador. PMID:26583534

Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases.

PubMed

Gofshteyn, Jacqueline S; Wilfong, Angus; Devinsky, Orrin; Bluvstein, Judith; Charuta, Joshi; Ciliberto, Michael A; Laux, Linda; Marsh, Eric D

2017-01-01

Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.

Leiomyoma of Urinary Bladder Presenting with Febrile Urinary Tract Infection: A Case Report.

PubMed

Haddad, Ra'ed Ghassan; Murshidi, Mujalli Mhailan; Abu Shahin, Nisreen; Murshidi, Muayyad Mujalli

2016-01-01

Leiomyomas of urinary bladder constitute only about 0.43% of all bladder tumors. Only about 250 cases were reported in English literature. This is the first reported case of bladder leiomyoma to present with febrile urinary tract infection. We report a case of a 37- year old male who presented with febrile urinary tract infection. Imaging showed a bladder lesion. This lesion was managed by transurethral resection. Pathologic diagnosis was bladder leiomyoma. Although bladder leiomyomas are benign, they can cause serious sequelae, including serious urinary tract infections as the case we present here shows. This is why it is important to early diagnose and treat this condition. This case highlights the importance of early introduction of imaging in patients presenting with severe urinary tract infections. Failure to diagnose this lesion as the underlying cause of infection may have easily led to recurrence of similar severe life-threatening infections. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Prospective cohort study with active surveillance for fever in four dengue endemic countries in Latin America.

PubMed

Dayan, Gustavo; Arredondo, Jose L; Carrasquilla, Gabriel; Deseda, Carmen C; Dietze, Reynaldo; Luz, Kleber; Costa, Maria Selma N; Cunha, Rivaldo V; Rey, Luis C; Morales, Javier; Reynales, Humberto; Miranda, Maria; Zambrano, Betzana; Rivas, Enrique; Garbes, Pedro; Noriega, Fernando

2015-07-01

To prepare for a Phase III dengue vaccine efficacy trial, 20 investigational sites were selected for this observational study to identify dengue infections in a closed cohort (N = 3,000 children 9-16 years of age). Of 255 acute febrile episodes experienced by 235 children, 50 (21.3%) were considered serologically probable dengue, and 18 (7.7%) were considered virologically confirmed (i.e., dengue NS1 antigen positive) dengue cases. Considering the disease-free and at-risk period from study start to onset of symptoms, the overall incidence density of acute febrile episodes was 17.7 per 100 person-years of follow-up, ranging from 15.3 in Colombia to 22.0 in Puerto Rico. This study showed that all sites were capable of capturing and following up acute febrile episodes within a specific timeframe among the established cohort and to detect dengue cases. © The American Society of Tropical Medicine and Hygiene.

Brucellosis among Hospitalized Febrile Patients in Northern Tanzania

PubMed Central

Bouley, Andrew J.; Biggs, Holly M.; Stoddard, Robyn A.; Morrissey, Anne B.; Bartlett, John A.; Afwamba, Isaac A.; Maro, Venance P.; Kinabo, Grace D.; Saganda, Wilbrod; Cleaveland, Sarah; Crump, John A.

2012-01-01

Acute and convalescent serum samples were collected from febrile inpatients identified at two hospitals in Moshi, Tanzania. Confirmed brucellosis was defined as a positive blood culture or a ≥ 4-fold increase in microagglutination test titer, and probable brucellosis was defined as a single reciprocal titer ≥ 160. Among 870 participants enrolled in the study, 455 (52.3%) had paired sera available. Of these, 16 (3.5%) met criteria for confirmed brucellosis. Of 830 participants with ≥ 1 serum sample, 4 (0.5%) met criteria for probable brucellosis. Brucellosis was associated with increased median age (P = 0.024), leukopenia (odds ratio [OR] 7.8, P = 0.005), thrombocytopenia (OR 3.9, P = 0.018), and evidence of other zoonoses (OR 3.2, P = 0.026). Brucellosis was never diagnosed clinically, and although all participants with brucellosis received antibacterials or antimalarials in the hospital, no participant received standard brucellosis treatment. Brucellosis is an underdiagnosed and untreated cause of febrile disease among hospitalized adult and pediatric patients in northern Tanzania. PMID:23091197

Leptospirosis among Hospitalized Febrile Patients in Northern Tanzania

PubMed Central

Biggs, Holly M.; Bui, Duy M.; Galloway, Renee L.; Stoddard, Robyn A.; Shadomy, Sean V.; Morrissey, Anne B.; Bartlett, John A.; Onyango, Jecinta J.; Maro, Venance P.; Kinabo, Grace D.; Saganda, Wilbrod; Crump, John A.

2011-01-01

We enrolled consecutive febrile admissions to two hospitals in Moshi, Tanzania. Confirmed leptospirosis was defined as a ≥ 4-fold increase in microscopic agglutination test (MAT) titer; probable leptospirosis as reciprocal MAT titer ≥ 800; and exposure to pathogenic leptospires as titer ≥ 100. Among 870 patients enrolled in the study, 453 (52.1%) had paired sera available, and 40 (8.8%) of these met the definition for confirmed leptospirosis. Of 832 patients with ≥ 1 serum sample available, 30 (3.6%) had probable leptospirosis and an additional 277 (33.3%) had evidence of exposure to pathogenic leptospires. Among those with leptospirosis the most common clinical diagnoses were malaria in 31 (44.3%) and pneumonia in 18 (25.7%). Leptospirosis was associated with living in a rural area (odds ratio [OR] 3.4, P < 0.001). Among those with confirmed leptospirosis, the predominant reactive serogroups were Mini and Australis. Leptospirosis is a major yet underdiagnosed cause of febrile illness in northern Tanzania, where it appears to be endemic. PMID:21813847

Flea-Borne Rickettsioses in the North of Caldas Province, Colombia

PubMed Central

Montoya, Viviana; Martínez, Alejandra; Mercado, Marcela; De la Ossa, Alberto; Vélez, Carolina; Estrada, Gloria; Pérez, Jorge E.; Faccini-Martínez, Alvaro A.; Labruna, Marcelo B.; Valbuena, Gustavo

2013-01-01

Abstract Rickettsia typhi and R. felis are the etiological agents of murine typhus and flea-borne spotted fever, respectively. Both are emerging acute febrile zoonotic diseases for which fleas are vectors; they also have similar clinical characteristics and global distribution. In 2005, we identified the circulation of murine typhus in 6 towns within the mountainous coffee-growing area north of Caldas, Colombia. We now report the specific seroprevalence against R. typhi and R. felis, and associated risk factors in 7 towns of this province. The combined seroprevalence against the 2 flea-borne rickettsioses is the highest yet reported in the literature: 71.7% (17.8% for R. felis, 25.2% for R. typhi, and 28.7% for both). We also report a prospective analysis of 26 patients with a febrile illness compatible with rickettsioses, including murine typhus; 9 of these patients had a rickettsiosis. This supports our sero-epidemiological results and highlights the diagnostic complexity of febrile syndromes in this region. PMID:23473218

[Results of a post-marketing surveillance of meropenem for febrile neutropenia].

PubMed

Wakisaka, Koji; Tani, Shunsuke; Ishibashi, Kazuo; Nukui, Kazuhiko; Nagao, Munehiko

2015-08-01

The post-marketing surveillance of meropenem (Meropen) for febrile neutropenia (FN) was conducted between July 2010 and June 2012 to evaluate safety and efficacy under actual clinical use. There were 1191 and 1124 evaluable cases for safety and efficacy respectively, of 1207 case cards collected from 180 institutions. In safety analysis, the incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 15.7% (187/1191 cases), and the main ADRs were alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, hepatic function abnormal, and liver disorder, which were similar to these observed in the clinical study for FN or post marketing surveillances of meropenem conducted before. In efficacy analysis, the overall efficacy was 81.8% (919/1124 cases). Also, it was 79.2% (708/894 cases) for hematological malignancy and 91.8% (213/232 cases) for solid cancer. These results confirmed meropenem (Meropen) is one of the well-tolerated and potent antimicrobial agents for febrile neutropenia.

[Experience of diagnosis and treatment of exogenous high-grade fever].

PubMed

Xiong, Xing-jiang; Wang, Jie

2011-06-01

There is a regular pattern in the diagnosis and treatment of exogenous high-grade fever, of which the key point is formula syndrome identification. Syndrome differentiation of the six channels is appropriate for not only exogenous cold but also various other conditions. The diagnosis and treatment of high-grade fever can also follow the law of syndrome differentiation of the six channels. The theory of epidemic febrile diseases stems from and elaborates on an understanding of exogenous febrile conditions, so many effective formulas used to treat epidemic febrile diseases also have great value in the treatment of high-grade fever. Deteriorated syndrome, which is central to this condition, is very commonly seen in cases of high-grade fever, the key therapeutic principle of which is established according to syndromes. Allowing analysis that does not rigidly adhere to either established modern diagnosis or traditional Chinese syndromes, prominent achievements could be made in treating high-grade fever by summarizing the regular presenting patterns in terms of the constitution and symptoms.

Management of Breast Cancer Patients with Chemotherapy-Induced Neutropenia or Febrile Neutropenia

PubMed Central

Fontanella, Caterina; Bolzonello, Silvia; Lederer, Bianca; Aprile, Giuseppe

2014-01-01

Summary Chemotherapy-induced neutropenia (CIN) is a common toxicity caused by the administration of anticancer drugs. This side effect is associated with life-threatening infections and may alter the chemotherapy schedule, thus impacting on early and long-term outcomes. Elderly breast cancer patients with impaired health status or advanced disease as well as patients undergoing dose-dense anthracycline/taxane- or docetaxel-based regimens have the highest risk of CIN. A careful assessment of the baseline risk for CIN allows the selection of patients who need primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) and/or antimicrobial agents. Neutropenic cancer patients may develop febrile neutropenia and CIN-related severe medical complications. Specific risk assessment scores, along with comprehensive clinical evaluation, are able to define a group of febrile patients with low risk for complications who can be safely treated as outpatients. Conversely, patients with higher risk of severe complications should be hospitalized and should receive intravenous antibiotic therapy with or without G-CSF. PMID:25404882

The role of ¹⁸F-FDG PET/CT for the diagnosis of infections in patients with hematological malignancies and persistent febrile neutropenia.

PubMed

Gafter-Gvili, Anat; Paul, Mical; Bernstine, Hanna; Vidal, Liat; Ram, Ron; Raanani, Pia; Yeshurun, Moshe; Tadmor, Boaz; Leibovici, Leonard; Shpilberg, Ofer; Groshar, David

2013-09-01

We assessed the performance of PET/CT for diagnosis and management of infections in high-risk hematological cancer patients with persistent febrile neutropenia in a prospective study. (18)F-FDG PET/CT with contrast-enhanced CT was performed on day 5-7 of persistent fever. Between 2008 and 2011, 91 PET/CT examinations were performed for different episodes in 79 patients, resulting in 117 diagnoses. The sensitivity of the PET/CT was 79.8% (71/89) compared to 51.7% (46/89) with chest/sinus CT alone. Specificities were 32.14% (9/28) vs. 42.85% (12/28), respectively. PET/CT resulted in a change from the pre-test diagnosis in 63/91 (69%) of episodes and in modification of patients' management in 46/91 (55%). PET/CT was beneficial in diagnosing abdominal infections. PET/CT has a potential role in the diagnostic evaluation of patients with persistent febrile neutropenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Extended-spectrum β-lactamase-producing bacteria caused less than 5% of urinary tract infections in a paediatric emergency centre.

PubMed

Jacmel, Lisa; Timsit, Sandra; Ferroni, Agnès; Auregan, Clémentine; Angoulvant, François; Chéron, Gérard

2017-01-01

The last decade has seen a significant increase in extended-spectrum β-lactamase (ESBL) secreting organisms responsible for paediatric urinary tract infections (UTIs), particularly in community-acquired infections. These expose patients to the risks of antibiotic treatment failure and renal scarring. This prospective study examined the prevalence and risk factors of febrile ESBL UTIs and their treatment in the paediatric emergency department of a university hospital. In this prospective observational study, all children from 0 to 16 years of age with febrile UTIs were included from May 2012 to April 2013. Cases with and without ESBL involvement were compared. Of the 474 diagnosed febrile UTIs, 22 (4.6%) with a 95% confidence interval (95% CI) of 2.9-6.9 were due to an ESBL-producing organism. Escherichia coli was found in 85% of cases. Significant odds ratios (OR) for ESBL urinary tract infections were prior hospitalisation (OR 4.1, 95% CI 1.6-10.8), urinary tract abnormalities (OR 3.9, 95% CI 1.5-10.2) and previous antibiotic treatment (OR 3.1, 95% CI 1.2-8.8). All ESBL urinary tract infections had positive outcomes. The prevalence of febrile ESBL urinary tract infections was less than 5% in a paediatric emergency department. This low rate was not high enough to justify changing our guidelines. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Long-term consequences of a prolonged febrile seizure in a dual pathology model.

PubMed

Gibbs, Steve; Chattopadhyaya, Bidisha; Desgent, Sébastien; Awad, Patricia N; Clerk-Lamalice, Olivier; Levesque, Maxime; Vianna, Rose-Mari; Rébillard, Rose-Marie; Delsemme, Andrée-Anne; Hébert, David; Tremblay, Luc; Lepage, Martin; Descarries, Laurent; Di Cristo, Graziella; Carmant, Lionel

2011-08-01

Clinical evidence suggests that febrile status epilepticus (SE) in children can lead to acute hippocampal injury and subsequent temporal lobe epilepsy. The contribution of febrile SE to the mechanisms underlying temporal lobe epilepsy are however poorly understood. A rat model of temporal lobe epilepsy following hyperthermic SE was previously established in our laboratory, wherein a focal cortical lesion induced at postnatal day 1 (P1), followed by a hyperthermic SE (more than 30 min) at P10, leads to hippocampal atrophy at P22 (dual pathology model) and spontaneous recurrent seizures (SRS) with mild visuospatial memory deficits in adult rats. The goal of this study was to identify the long term electrophysiological, anatomical and molecular changes in this model. Following hyperthermic SE, all cortically lesioned pups developed progressive SRS as adults, characterized by the onset of highly rhythmic activity in the hippocampus. A reduction of hippocampal volume on the side of the lesion preceded the SRS and was associated with a loss of hippocampal neurons, a marked decrease in pyramidal cell spine density, an increase in the hippocampal levels of NMDA receptor NR2A subunit, but no significant change in GABA receptors. These findings suggest that febrile SE in the abnormal brain leads to hippocampal injury that is followed by progressive network reorganization and molecular changes that contribute to the epileptogenesis as well as the observed memory deficits. Copyright © 2011 Elsevier Inc. All rights reserved.

Hemorrhagic fever with renal syndrome and Crimean-Congo hemorrhagic fever as causes of acute undifferentiated febrile illness in Bulgaria.

PubMed

Christova, Iva; Younan, Rasha; Taseva, Evgenia; Gladnishka, Teodora; Trifonova, Iva; Ivanova, Vladislava; Spik, Kristin; Schmaljohn, Connie; Mohareb, Emad

2013-03-01

Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are the 2 widespread viral hemorrhagic fevers occurring in Europe. HFRS is distributed throughout Europe, and CCHF has been reported mainly on the Balkan Peninsula and Russia. Both hemorrhagic fevers are endemic in Bulgaria. We investigated to what extent acute undifferentiated febrile illness in Bulgaria could be due to hantaviruses or to CCHF virus. Using enzyme-linked immunosorbent assays (ELISAs), we tested serum samples from 527 patients with acute febrile illness for antibodies against hantaviruses and CCHF virus. Immunoglobulin M (IgM) antibodies against hantaviruses were detected in 15 (2.8%) of the patients. Of the 15 hantavirus-positive patients, 8 (1.5%) were positive for Dobrava virus (DOBV), 5 (0.9%) were positive for Puumala virus (PUUV), and the remaining 2 were positive for both hantaviruses. A plaque reduction neutralization test (PRNT) confirmed 4 of the 10 DOBV-positive samples. PRNT was negative for all PUUV-positive samples. Serologic evidence of recent CCHF virus infection was found in 13 (2.5%) of the patients. Interestingly, HFRS and CCHF were not only detected in well-known endemic areas of Bulgaria but also in nonendemic regions. Our results suggested that in endemic countries, CCHF and/or HFRS might appear as a nonspecific febrile illness in a certain proportion of patients. Physicians must be aware of possible viral hemorrhagic fever cases, even if hemorrhages or renal impairment are not manifested.

Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children.

PubMed

Kim, Hyun Hee; Chung, Mi Hae; Bin, Joong Hyun; Cho, Kyoung Soon; Lee, Juyoung; Suh, Jin Soon

2018-01-01

Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (P<0.001). The area under the ROC curve for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine. © The Korean Society for Laboratory Medicine

Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children

PubMed Central

Kim, Hyun Hee; Chung, Mi Hae; Bin, Joong Hyun; Cho, Kyoung Soon; Lee, Juyoung

2018-01-01

Background Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. Methods In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. Results The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (P<0.001). The area under the ROC curve for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. Conclusions Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine. PMID:29071817

Prevention of urinary tract infections by antibiotic cycling in spinal cord injury patients and low emergence of multidrug resistant bacteria.

PubMed

Poirier, C; Dinh, A; Salomon, J; Grall, N; Andremont, A; Bernard, L

2016-09-01

Urinary tract infections (UTIs) are a major recurrent problem for spinal cord injury (SCI) patients. Repeated antibiotic treatments contribute to the emergence of multidrug-resistant bacteria (MDRB). We evaluated the use of weekly oral cycling antibiotics (WOCA) in the prevention of UTIs over a mean follow-up period of 53 months (median follow-up period: 57 months) and analyzed the risk of MDRB emergence. We conducted a cross-sectional study of adult SCI patients with neurogenic bladder who were receiving the WOCA regimen. We included 50 patients, mainly men (60%), with a mean age of 51±13.5 years. Overall, 66% of patients had been paraplegic or tetraplegic for 19.4±14.3 years; 92% underwent intermittent catheterization; and 36% had no postvoid residual. The number of febrile and non-febrile UTIs significantly reduced after WOCA initiation (9.45 non-febrile UTIs before WOCA initiation vs. 1.57 after; 2.25 febrile UTIs before WOCA initiation vs. 0.18 after; P=0.0001). Only one adverse event was reported during the follow-up period. The number of MDRB-colonized patients decreased from 9/50 to 4/50 during the follow-up period. WOCA is an effective and safe strategy to prevent UTIs in SCI patients with neurogenic bladder. WOCA does not lead to the emergence of MDRB resistance and even seems to reduce MDRB carriage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Calcium channel blockers inhibit endogenous pyrogen fever in rats and rabbits.

PubMed

Stitt, J T; Shimada, S G

1991-09-01

We have previously shown that febrile responses in both rats and rabbits are elicited by the intravenous injection of a semipurified endogenous pyrogen (EP) prepared from human monocytes. We are now presenting evidence that these febrile responses are mediated via activation of Ca2+ channels by EP. The febrile responses of male New Zealand White rabbits and Sprague-Dawley rats to a standard dose of EP were determined at their respective thermoneutral ambient temperatures. The animals were then treated with Ca2+ channel blocker verapamil (7.5 mg/kg iv) 30-60 min before the EP challenge. In every case the febrile response to EP was markedly attenuated after verapamil pretreatment, while administration of verapamil by itself had no detectable effect on body temperature. Another Ca2+ channel blocker, nifedipine (5 mg/kg iv), was shown to possess antipyretic activity in rats also. To localize where in the fever pathway these Ca2+ channel blockers were acting, we investigated the effect of verapamil at the same dose on fevers that were produced by microinjection of prostaglandin E (PGE) directly into the brain. These PGE fevers were unaffected by verapamil pretreatment, indicating that the antipyretic action of Ca2+ channel blockers occurs before the formation of PGE in response to EP stimulation. The most likely locus of action is the activation of the enzyme phospholipase A2, which regulates the production of arachidonic acid from cellular phospholipids in the prostanoid cascade.

Central mediators involved in the febrile response: effects of antipyretic drugs

PubMed Central

Zampronio, Aleksander R; Soares, Denis M; Souza, Glória E P

2015-01-01

Fever is a complex signal of inflammatory and infectious diseases. It is generally initiated when peripherally produced endogenous pyrogens reach areas that surround the hypothalamus. These peripheral endogenous pyrogens are cytokines that are produced by leukocytes and other cells, the most known of which are interleukin-1β, tumor necrosis factor-α, and interleukin-6. Because of the capacity of these molecules to induce their own synthesis and the synthesis of other cytokines, they can also be synthesized in the central nervous system. However, these pyrogens are not the final mediators of the febrile response. These cytokines can induce the synthesis of cyclooxygenase-2, which produces prostaglandins. These prostanoids alter hypothalamic temperature control, leading to an increase in heat production, the conservation of heat, and ultimately fever. The effect of antipyretics is based on blocking prostaglandin synthesis. In this review, we discuss recent data on the importance of prostaglandins in the febrile response, and we show that some endogenous mediators can still induce the febrile response even when known antipyretics reduce the levels of prostaglandins in the central nervous system. These studies suggest that centrally produced mediators other than prostaglandins participate in the genesis of fever. Among the most studied central mediators of fever are corticotropin-releasing factor, endothelins, chemokines, endogenous opioids, and substance P, which are discussed herein. Additionally, recent evidence suggests that these different pathways of fever induction may be activated during different pathological conditions. PMID:27227071

Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.

PubMed

Yoshida, M; Karasawa, M; Naruse, T; Fukuda, M; Hirashima, K; Oh, H; Ninomiya, H; Abe, T; Saito, K; Shishido, H; Moriyama, Y; Shibata, A; Motoyoshi, K; Nagata, N; Miura, Y

1999-02-01

The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

Mannose-binding lectin 2 polymorphisms do not influence frequency or type of infection in adults with chemotherapy induced neutropaenia.

PubMed

Wong, Michelle; Öhrmalm, Lars; Broliden, Kristina; Aust, Carl; Hibberd, Martin; Tolfvenstam, Thomas

2012-01-01

Mannose-binding Lectin protein (MBL) has been suggested to be relevant in the defence against infections in immunosuppressed individuals. In a Swedish adult cohort immunosuppressed from both the underlying disease and from iatrogenic treatments for their underlying disease we investigated the role of MBL in susceptibility to infection. In this cross sectional, prospective study, blood samples obtained from 96 neutropaenic febrile episodes, representing 82 individuals were analysed for single nucleotide polymorphism (SNP) in the MBL2 gene. Concurrent measurement of plasma MBL protein concentrations was also performed for observation of acute response during febrile episodes. No association was observed between MBL2 genotype or plasma MBL concentrations, and the type or frequency of infection. Adding to the literature, we found no evidence that viral infections or co-infections with virus and bacteria would be predisposed by MBL deficiency. We further saw no correlation between MBL2 genotype and the risk of fever. However, fever duration in febrile neutropaenic episodes was negatively associated with MBL2 SNP mutations (p<0.05). Patients with MBL2 SNP mutations presented a median febrile duration of 1.8 days compared with 3 days amongst patients with wildtype MBL2 genotype. We found no clear association between infection, or infection type to MBL2 genotypes or plasma MBL concentration, and add to the reports casting doubts on the benefit of recombinant MBL replacement therapy use during iatrogenic neutropaenia.

Mannose-Binding Lectin 2 Polymorphisms Do Not Influence Frequency or Type of Infection in Adults with Chemotherapy Induced Neutropaenia

PubMed Central

Wong, Michelle; Öhrmalm, Lars; Broliden, Kristina; Aust, Carl; Hibberd, Martin; Tolfvenstam, Thomas

2012-01-01

Background Mannose-binding Lectin protein (MBL) has been suggested to be relevant in the defence against infections in immunosuppressed individuals. In a Swedish adult cohort immunosuppressed from both the underlying disease and from iatrogenic treatments for their underlying disease we investigated the role of MBL in susceptibility to infection. Methods In this cross sectional, prospective study, blood samples obtained from 96 neutropaenic febrile episodes, representing 82 individuals were analysed for single nucleotide polymorphism (SNP) in the MBL2 gene. Concurrent measurement of plasma MBL protein concentrations was also performed for observation of acute response during febrile episodes. Findings No association was observed between MBL2 genotype or plasma MBL concentrations, and the type or frequency of infection. Adding to the literature, we found no evidence that viral infections or co-infections with virus and bacteria would be predisposed by MBL deficiency. We further saw no correlation between MBL2 genotype and the risk of fever. However, fever duration in febrile neutropaenic episodes was negatively associated with MBL2 SNP mutations (p<0.05). Patients with MBL2 SNP mutations presented a median febrile duration of 1.8 days compared with 3 days amongst patients with wildtype MBL2 genotype. Interpretation We found no clear association between infection, or infection type to MBL2 genotypes or plasma MBL concentration, and add to the reports casting doubts on the benefit of recombinant MBL replacement therapy use during iatrogenic neutropaenia. PMID:22363494

Pentraxin 3 predicts complicated course of febrile neutropenia in haematological patients, but the decision level depends on the underlying malignancy.

PubMed

Juutilainen, Auni; Vänskä, Matti; Pulkki, Kari; Hämäläinen, Sari; Nousiainen, Tapio; Jantunen, Esa; Koivula, Irma

2011-11-01

This study aimed at assessing the cut-off levels for pentraxin 3 (PTX3) in predicting complications of neutropenic fever (bacteraemia, septic shock) in haematological patients. A prospective study during 2006-2009 was performed at haematology ward in Kuopio University Hospital. A patient was eligible for the study if having neutropenic fever after intensive therapy for acute myeloid leukaemia (AML) (n = 32) or non-Hodgkin lymphoma (NHL) (n = 35). Blood cultures were taken, and maximal PTX3 and C-reactive protein (CRP) were evaluated during d0 to d3 from the beginning of fever onset. The level of PTX3 was associated with both the underlying malignancy and the presence of complications, with highest level in NHL patients with complicated course of febrile neutropenia and lowest in AML patients with non-complicated course. The cut-off level of PTX3 to predict complications was ten-fold in patients with NHL (115 μg/L) in comparison with patients with AML (11.5 μg/L). In combined analysis based on separate cut-offs, PTX3 predicted complications of febrile neutropenia with sensitivity of 0.86, specificity of 0.83, positive predictive value of 0.57 and negative predictive value of 0.96.   PTX3 was superior to CRP in predicting complicated course of febrile neutropenia, but only when the effect of the underlying malignancy had been taken into account. © 2011 John Wiley & Sons A/S.

Neural Correlates of Early Sound Encoding and their Relationship to Speech-in-Noise Perception

PubMed Central

Coffey, Emily B. J.; Chepesiuk, Alexander M. P.; Herholz, Sibylle C.; Baillet, Sylvain; Zatorre, Robert J.

2017-01-01

Speech-in-noise (SIN) perception is a complex cognitive skill that affects social, vocational, and educational activities. Poor SIN ability particularly affects young and elderly populations, yet varies considerably even among healthy young adults with normal hearing. Although SIN skills are known to be influenced by top-down processes that can selectively enhance lower-level sound representations, the complementary role of feed-forward mechanisms and their relationship to musical training is poorly understood. Using a paradigm that minimizes the main top-down factors that have been implicated in SIN performance such as working memory, we aimed to better understand how robust encoding of periodicity in the auditory system (as measured by the frequency-following response) contributes to SIN perception. Using magnetoencephalograpy, we found that the strength of encoding at the fundamental frequency in the brainstem, thalamus, and cortex is correlated with SIN accuracy. The amplitude of the slower cortical P2 wave was previously also shown to be related to SIN accuracy and FFR strength; we use MEG source localization to show that the P2 wave originates in a temporal region anterior to that of the cortical FFR. We also confirm that the observed enhancements were related to the extent and timing of musicianship. These results are consistent with the hypothesis that basic feed-forward sound encoding affects SIN perception by providing better information to later processing stages, and that modifying this process may be one mechanism through which musical training might enhance the auditory networks that subserve both musical and language functions. PMID:28890684

Gas diffusion ultrabarriers on polymer substrates using Al2O3 atomic layer deposition and SiN plasma-enhanced chemical vapor deposition

NASA Astrophysics Data System (ADS)

Carcia, P. F.; McLean, R. S.; Groner, M. D.; Dameron, A. A.; George, S. M.

2009-07-01

Thin films grown by Al2O3 atomic layer deposition (ALD) and SiN plasma-enhanced chemical vapor deposition (PECVD) have been tested as gas diffusion barriers either individually or as bilayers on polymer substrates. Single films of Al2O3 ALD with thicknesses of ≥10 nm had a water vapor transmission rate (WVTR) of ≤5×10-5 g/m2 day at 38 °C/85% relative humidity (RH), as measured by the Ca test. This WVTR value was limited by H2O permeability through the epoxy seal, as determined by the Ca test for the glass lid control. In comparison, SiN PECVD films with a thickness of 100 nm had a WVTR of ˜7×10-3 g/m2 day at 38 °C/85% RH. Significant improvements resulted when the SiN PECVD film was coated with an Al2O3 ALD film. An Al2O3 ALD film with a thickness of only 5 nm on a SiN PECVD film with a thickness of 100 nm reduced the WVTR from ˜7×10-3 to ≤5×10-5 g/m2 day at 38 °C/85% RH. The reduction in the permeability for Al2O3 ALD on the SiN PECVD films was attributed to either Al2O3 ALD sealing defects in the SiN PECVD film or improved nucleation of Al2O3 ALD on SiN.

Effect of SiN x diffusion barrier thickness on the structural properties and photocatalytic activity of TiO2 films obtained by sol-gel dip coating and reactive magnetron sputtering.

PubMed

Ghazzal, Mohamed Nawfal; Aubry, Eric; Chaoui, Nouari; Robert, Didier

2015-01-01

We investigate the effect of the thickness of the silicon nitride (SiN x ) diffusion barrier on the structural and photocatalytic efficiency of TiO2 films obtained with different processes. We show that the structural and photocatalytic efficiency of TiO2 films produced using soft chemistry (sol-gel) and physical methods (reactive sputtering) are affected differentially by the intercalating SiN x diffusion barrier. Increasing the thickness of the SiN x diffusion barrier induced a gradual decrease of the crystallite size of TiO2 films obtained by the sol-gel process. However, TiO2 obtained using the reactive sputtering method showed no dependence on the thickness of the SiN x barrier diffusion. The SiN x barrier diffusion showed a beneficial effect on the photocatalytic efficiency of TiO2 films regardless of the synthesis method used. The proposed mechanism leading to the improvement in the photocatalytic efficiency of the TiO2 films obtained by each process was discussed.

Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity.

PubMed

Witteveen, Josefine S; Willemsen, Marjolein H; Dombroski, Thaís C D; van Bakel, Nick H M; Nillesen, Willy M; van Hulten, Josephus A; Jansen, Eric J R; Verkaik, Dave; Veenstra-Knol, Hermine E; van Ravenswaaij-Arts, Conny M A; Wassink-Ruiter, Jolien S Klein; Vincent, Marie; David, Albert; Le Caignec, Cedric; Schieving, Jolanda; Gilissen, Christian; Foulds, Nicola; Rump, Patrick; Strom, Tim; Cremer, Kirsten; Zink, Alexander M; Engels, Hartmut; de Munnik, Sonja A; Visser, Jasper E; Brunner, Han G; Martens, Gerard J M; Pfundt, Rolph; Kleefstra, Tjitske; Kolk, Sharon M

2016-08-01

Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development.

Fuzzy adaptive integration scheme for low-cost SINS/GPS navigation system

NASA Astrophysics Data System (ADS)

Nourmohammadi, Hossein; Keighobadi, Jafar

2018-01-01

Due to weak stand-alone accuracy as well as poor run-to-run stability of micro-electro mechanical system (MEMS)-based inertial sensors, special approaches are required to integrate low-cost strap-down inertial navigation system (SINS) with global positioning system (GPS), particularly in long-term applications. This paper aims to enhance long-term performance of conventional SINS/GPS navigation systems using a fuzzy adaptive integration scheme. The main concept behind the proposed adaptive integration is the good performance of attitude-heading reference system (AHRS) in low-accelerated motions and its degradation in maneuvered or accelerated motions. Depending on vehicle maneuvers, gravity-based attitude angles can be intelligently utilized to improve orientation estimation in the SINS. Knowledge-based fuzzy inference system is developed for decision-making between the AHRS and the SINS according to vehicle maneuvering conditions. Inertial measurements are the main input data of the fuzzy system to determine the maneuvering level during the vehicle motions. Accordingly, appropriate weighting coefficients are produced to combine the SINS/GPS and the AHRS, efficiently. The assessment of the proposed integrated navigation system is conducted via real data in airborne tests.

Piperacillin/tazobactam: a pharmacoeconomic review of its use in moderate to severe bacterial infections.

PubMed

Young, M; Plosker, G L

2001-01-01

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models. Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.

Cultural categorization of febrile illnesses in correlation with herbal remedies used for treatment in Southwestern Nigeria.

PubMed

Ajaiyeoba, E O; Oladepo, O; Fawole, O I; Bolaji, O M; Akinboye, D O; Ogundahunsi, O A T; Falade, C O; Gbotosho, G O; Itiola, O A; Happi, T C; Ebong, O O; Ononiwu, I M; Osowole, O S; Oduola, O O; Ashidi, J S; Oduola, A M J

2003-04-01

The ethnographic study was conducted in two communities in Oyo State in Southwestern Nigeria. The study sites consisted of a rural and an urban local government area located in the tropical rain forest zone of Nigeria. The study was designed to obtain information on febrile illnesses and herbal remedies for treatment with the aim of identifying potential antimalarial drugs. The study revealed that fever is a general term for describing illnesses associated with elevated body temperature. The indigenous Yoruba ethnic population has categorized fever based on symptoms and causes. The present communication is the result of focus group discussion and semi-structured questionnaire administered to traditional healers, herb sellers, elders and mothers. This was on types of fevers, symptoms and causes of febrile illnesses. The investigation also included use of traditional herbs in the prevention and treatment of the illnesses in the two communities.A total of 514 respondents were interviewed. This was made up of 266 (51.8%) from Atiba local government area (LGA), an urban centre while 248 (48.2%) respondents were interviewed from Itesiwaju LGA, a rural community. The LGAs are located in Oyo State of Nigeria. The respondents proffered 12 types of febrile illnesses in a multiple response answering system in Yoruba language. The most common ones (direct translation into English) were: yellow fever (39.1%), typhoid (34.8%), ordinary (28.8%), rainy season (20.8%) and headache (10.5%) fevers, respectively. Perceived causes of each of the febrile illnesses included stress, mosquito bites, unclean water, rains and over exposure to the sun. Methods of fever prevention were mainly with the use of herbal decoctions, powdered herbs, orthodox medications and maintenance of proper hygiene. Of a total of 112 different herbal remedies used in the treatment of the febrile illnesses compiled from the study, 25 recipes are presented. Recipes consisted of 2-7 ingredients. Oral decoctions (84%), oral powders (63%), use as soaps and creams (40%) in a multiple response system, were the most prevalent routes of administration of prepared herbs used in the treatment of the fevers. Boiling in water or alcohol was the most common method used in the preparation of the remedies. The four most frequently mentioned (multiple response system) plants in the Southwest ethnobotany for fevers were Azadirachta indica (87.5%), Mangifera indica (75.0%), Morinda lucida (68.8%) and Citrus medica (68.8%).

Clinical prediction models for young febrile infants at the emergency department: an international validation study.

PubMed

Vos-Kerkhof, Evelien de; Gomez, Borja; Milcent, Karen; Steyerberg, Ewout W; Nijman, Ruud Gerard; Smit, Frank J; Mintegi, Santiago; Moll, Henriette A; Gajdos, Vincent; Oostenbrink, Rianne

2018-05-24

To assess the diagnostic value of existing clinical prediction models (CPM; ie, statistically derived) in febrile young infants at risk for serious bacterial infections. A systematic literature review identified eight CPMs for predicting serious bacterial infections in febrile children. We validated these CPMs on four validation cohorts of febrile children in Spain (age <3 months), France (age <3 months) and two cohorts in the Netherlands (age 1-3 months and >3-12 months). We evaluated the performance of the CPMs by sensitivity/specificity, area under the receiver operating characteristic curve (AUC) and calibration studies. The original cohorts in which the prediction rules were developed (derivation cohorts) ranged from 381 to 15 781 children, with a prevalence of serious bacterial infections varying from 0.8% to 27% and spanned an age range of 0-16 years. All CPMs originally performed moderately to very well (AUC 0.60-0.93). The four validation cohorts included 159-2204 febrile children, with a median age range of 1.8 (1.2-2.4) months for the three cohorts <3 months and 8.4 (6.0-9.6) months for the cohort >3-12 months of age. The prevalence of serious bacterial infections varied between 15.1% and 17.2% in the three cohorts <3 months and was 9.8% for the cohort >3-12 months of age. Although discriminative values varied greatly, best performance was observed for four CPMs including clinical signs and symptoms, urine dipstick analyses and laboratory markers with AUC ranging from 0.68 to 0.94 in the three cohorts <3 months (ranges sensitivity: 0.48-0.94 and specificity: 0.71-0.97). For the >3-12 months' cohort AUC ranges from 0.80 to 0.89 (ranges sensitivity: 0.70-0.82 and specificity: 0.78-0.90). In general, the specificities exceeded sensitivities in our cohorts, in contrast to derivation cohorts with high sensitivities, although this effect was stronger in infants <3 months than in infants >3-12 months. We identified four CPMs, including clinical signs and symptoms, urine dipstick analysis and laboratory markers, which can aid clinicians in identifying serious bacterial infections. We suggest clinicians should use CPMs as an adjunctive clinical tool when assessing the risk of serious bacterial infections in febrile young infants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of peripheral and central capillary refill time in febrile children presenting to a paediatric emergency department and its utility in identifying children with serious bacterial infection.

PubMed

de Vos-Kerkhof, Evelien; Krecinic, Tarik; Vergouwe, Yvonne; Moll, Henriëtte A; Nijman, Ruud G; Oostenbrink, Rianne

2017-01-01

To determine the agreement between peripheral and central capillary refill time (pCRT/cCRT) and their diagnostic values for detecting serious bacterial infection (SBI) in febrile children attending the paediatric emergency department (ED). Prospective observational study. Paediatric ED, Erasmus Medium Care-Sophia Children's hospital, the Netherlands. 1193 consecutively included, previously healthy, febrile children (1 month-16 years) with both pCRT measurements and cCRT measurements available. SBI diagnosis was based on abnormal radiographic findings and/or positive cultures from normally sterile locations in addition to clinical criteria. Agreement between pCRT and cCRT (Cohen's κ), overall and stratified for age and body temperature. The diagnostic value of pCRT and cCRT for SBI was assessed with logistic regression. Overall agreement was 0.35 (95% CI 0.27 to 0.43; considered 'fair'). Although not significant, agreement was lower in children aged 1-<5 years (κ: 0.15 (95% CI 0.04 to 0.27)) and decreased with higher body temperatures with κ ranging from 0.55 (95% CI 0.32 to 0.79) for temperature <37.5°C to 0.21 (95% CI 0.07 to 0.34) for temperature >39.5°C. Abnormal pCRT (>2 s) was observed in 153 (12.8%; 95% CI 10.9% to 14.7%) and abnormal cCRT in 55 (4.6%; 95% CI 3.4% to 5.8%) children. The OR of abnormal pCRT (>2 s) for predicting SBI was 1.10 (95% CI 0.65 to 1.84). For abnormal cCRT (>2 s), the OR was 0.43 (95% CI 0.13 to 1.39). The pCRT and cCRT values showed only fair agreement in a general population of febrile children at the ED, and no significant association with age or body temperature was found. Only a small part of febrile children at risk for serious infections at the ED show abnormal CRT values. Both abnormal pCRT and cCRT (defined as >2 s) performed poorly and were non-significant in this study detecting SBI in a general population of febrile children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Mothers' perception of recovery and satisfaction with patent medicine dealers' treatment of childhood febrile conditions in rural communities.

PubMed

Ibeneme, Georgian Chiaka; Nwaneri, Ada Caroline; Ibeneme, Sam Chidi; Ezenduka, Pauline; Strüver, Vanessa; Fortwengel, Gehard; Okoye, Ifeoma Joy

2016-06-28

Infant mortality in rural areas of Nigeria can be minimized if childhood febrile conditions are treated by trained health personnel, deployed to primary healthcare centres (PHCs) rather than the observed preference of mothers for patent medicine dealers (PMDs). However, health service utilization/patronage is driven by consumer satisfaction and perception of services/product value. The objective of this study was to determine 'mothers' perception of recovery' and 'mothers' satisfaction' after PMD treatment of childhood febrile conditions, as likely drivers of mothers' health-seeking behaviour, which must be targeted to reverse the trend. Ugwuogo-Nike, in Enugu, Nigeria, has many PMDs/PHCs, and was selected based on high prevalence of childhood febrile conditions. In total, 385 consenting mothers (aged 15-45 years) were consecutively recruited at PMD shops, after purchasing drugs for childhood febrile conditions, in a cross-sectional observational study using a pre-tested instrument; 33 of them (aged 21-47 years) participated in focus group discussions (FGDs). Qualitative data were thematically analysed while a quantitative study was analysed with Z score and Chi square statistics, at p < 0.05. Most participants in FGDs perceived that their child had delayed recovery, but were satisfied with PMDs' treatment of childhood febrile conditions, for reasons that included politeness, caring attitude, drug availability, easy accessibility, flexibility in pricing, shorter waiting time, their God-fearing nature, and disposition as good listeners. Mothers' satisfaction with PMDs' treatment is significantly (p < 0.05) associated with mothers' perception of recovery of their child (χ(2) = 192.94, df = 4; p < 0.0001; Cramer's V = 0.7079). However, predicting mothers' satisfaction with PMDs' treatment from a knowledge of mothers' perception of recovery shows a high accord (lambda[A from B] = 0.8727), unlike when predicting mothers' perception of recovery based on knowledge of mothers' satisfaction with PMDs' treatment (lambda[A from B] = 0.4727). Mothers' satisfaction could be the key 'driver' of mothers' health-seeking behaviour and is less likely to be influenced by mothers' perception of recovery of their child. Therefore, mothers' negative perception of their child's recovery may not induce proportionate decline in mothers' health-seeking behaviour (patronage of PMDs), which might be influenced mainly by mothers' satisfaction with the positive attributes of PMDs' personality/practice and sets an important agenda for PHC reforms.

Febrile patients admitted to remote hospitals in Northeastern Kenya: seroprevalence, risk factors and a clinical prediction tool for Q-Fever.

PubMed

Njeru, J; Henning, K; Pletz, M W; Heller, R; Forstner, C; Kariuki, S; Fèvre, E M; Neubauer, H

2016-06-03

Q fever in Kenya is poorly reported and its surveillance is highly neglected. Standard empiric treatment for febrile patients admitted to hospitals is antimalarials or penicillin-based antibiotics, which have no activity against Coxiella burnetii. This study aimed to assess the seroprevalence and the predisposing risk factors for Q fever infection in febrile patients from a pastoralist population, and derive a model for clinical prediction of febrile patients with acute Q fever. Epidemiological and clinical data were obtained from 1067 patients from Northeastern Kenya and their sera tested for IgG antibodies against Coxiella burnetii antigens by enzyme-linked-immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA) and quantitative real-time PCR (qPCR). Logit models were built for risk factor analysis, and diagnostic prediction score generated and validated in two separate cohorts of patients. Overall 204 (19.1 %, 95 % CI: 16.8-21.6) sera were positive for IgG antibodies against phase I and/or phase II antigens or Coxiella burnetii IS1111 by qPCR. Acute Q fever was established in 173 (16.2 %, 95 % CI: 14.1-18.7) patients. Q fever was not suspected by the treating clinicians in any of those patients, instead working diagnosis was fever of unknown origin or common tropical fevers. Exposure to cattle (adjusted odds ratio [aOR]: 2.09, 95 % CI: 1.73-5.98), goats (aOR: 3.74, 95 % CI: 2.52-9.40), and animal slaughter (aOR: 1.78, 95 % CI: 1.09-2.91) were significant risk factors. Consumption of unpasteurized cattle milk (aOR: 2.49, 95 % CI: 1.48-4.21) and locally fermented milk products (aOR: 1.66, 95 % CI: 1.19-4.37) were dietary factors associated with seropositivity. Based on regression coefficients, we calculated a diagnostic score with a sensitivity 93.1 % and specificity 76.1 % at cut off value of 2.90: fever >14 days (+3.6), abdominal pain (+0.8), respiratory tract infection (+1.0) and diarrhoea (-1.1). Q fever is common in febrile Kenyan patients but underappreciated as a cause of community-acquired febrile illness. The utility of Q fever score and screening patients for the risky social-economic and dietary practices can provide a valuable tool to clinicians in identifying patients to strongly consider for detailed Q fever investigation and follow up on admission, and making therapeutic decisions.

Sinomenine attenuates renal fibrosis through Nrf2-mediated inhibition of oxidative stress and TGFβ signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Tian

Renal fibrosis is the common feature of chronic kidney disease and mainly mediated by TGFβ-associated pro-fibrogenic signaling, which causes excessive extracellular matrix accumulation and successive loss of kidney functions. Sinomenine (SIN), an alkaloid derived from medicinal herb extensively used in treatment of rheumatoid arthritis and various inflammatory disorders, displays renal protective properties in experimental animals; however its pharmacological potency against renal fibrosis is not explored. In this study we report that SIN possesses strong anti-renal fibrosis functions in kidney cell and in mouse fibrotic kidney. SIN beneficially modulated the pro-fibrogenic protein expression in TGFβ-treated kidney cells and attenuated the renalmore » fibrotic pathogenesis incurred by unilateral ureteral obstruction (UUO), which correlated with its activation of Nrf2 signaling - the key defender against oxidative stress with anti-fibrotic potentials. Further investigation on its regulation of Nrf2 downstream events revealed that SIN significantly balanced oxidative stress via improving the expression and activity of anti-oxidant and detoxifying enzymes, and interrupted the pro-fibrogenic signaling of TGFβ/Smad and Wnt/β-catenin. Even more impressively SIN achieved its anti-fibrotic activities in an Nrf2-dependent manner, suggesting that SIN regulation of Nrf2-associated anti-fibrotic activities constitutes a critical component of SIN's renoprotective functions. Collectively our studies have demonstrated a novel anti-fibrotic property of SIN and its upstream events and provided a molecular basis for SIN's potential applications in treatment of renal fibrosis-associated kidney disorders. - Highlights: • Sinomenine has strong potency of inhibiting renal fibrosis in UUO mouse kidney. • Sinomenine attenuates the expression of profibrogenic proteins. • Sinomenine balances renal fibrosis-associated oxidative stress. • Sinomenine mitigates profibrogenic signaling of TGBβ/Smad and Wnt/β-catenin. • Sinomenine exerts anti-renal fibrotic functions mainly via activating Nrf2 pathways.« less

Computation of the Quantities Describing the Lunar Librations in the Astronomical Almanac

DTIC Science & Technology

2010-08-01

this system ~e ( COS( -(3) cost >. + 180’ - tt)) cost -(3) sine>. + 180’ - tt) sin(-(3) , (1) Consid~r neXt, point M referred to axes OX’’z’ iIi...now write (7) as the three equl\\tions " cos b cos(1 + LM - tt) = cosj3 cost >. - tt - N) cos b sin(1 + LM - tt) ,= cos Lcosj3si,n(>’,- tt -’N) ,- sin...8217?’~ on . .the sel~~~centric sphere. The geocentric right ascension and declination of the Moon are 0:, 0 and so the right ascension and declination of

Pragmatic Idealism: Ernesto Che Guevaras Strategic Choice for Bolivia

DTIC Science & Technology

2017-06-01

that the guerrilla foco could be used as an inspiration to the masses, and that, by its very existence, people would be encouraged to support and join...Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE June 2017 3. REPORT TYPE AND...strategic, and psychological factors meant to achieve a specific end. 14. SUBJECT TERMS Che, Guevara, guerrilla warfare, Cuba, Bolivia

Biofunctionalized silicon nitride platform for sensing applications.

PubMed

Hoi, Hiofan; Rezaie, Salva S; Gong, Lu; Sen, Payel; Zeng, Hongbo; Montemagno, Carlo; Gupta, Manisha

2018-04-15

Silicon nitride (SiN x ) based biosensors have the potential to converge on the technological achievements of semiconductor microfabrication and biotechnology. Development of biofunctionalized SiN x surface and its integration with other devices will allow us to integrate the biosensing capability with probe control, data acquisition and data processing. Here we use the hydrogen plasma generated by inductively coupled plasma-reactive ion etching (ICP-RIE) technique to produce amino-functionality on the surface of SiN x which can then be readily used for biomolecule immobilization. ICP-RIE produces high-density hydrogen ions/radicals at low energy, which produces high-density amino group on the SiN x surface within a short duration of time and with minimal surface damage. In this work, we have demonstrated selective amination of SiN x surface as compared to Si surface. The as-activated SiN x surface can be readily biofunctionalized with both protein and oligonucleotide through covalent immobilization. N-5-azido-2-nitrobenzoyloxysuccinimide, a photoactivable amino reactive bifunctional crosslinker, was used and greater than 90% surface coverage was achieved for protein immobilization. In addition, ssDNA immobilization and hybridization with its complemented strand was shown. Thus, we demonstrate a uniform, reliable, fast and economical technique for creating biofunctionalized SiN x surface that can be used for developing compact high-sensitivity biosensors. Copyright © 2017 Elsevier B.V. All rights reserved.

Silicon Nitride Deposition for Flexible Organic Electronic Devices by VHF (162 MHz)-PECVD Using a Multi-Tile Push-Pull Plasma Source.

PubMed

Kim, Ki Seok; Kim, Ki Hyun; Ji, You Jin; Park, Jin Woo; Shin, Jae Hee; Ellingboe, Albert Rogers; Yeom, Geun Young

2017-10-19

Depositing a barrier film for moisture protection without damage at a low temperature is one of the most important steps for organic-based electronic devices. In this study, the authors investigated depositing thin, high-quality SiN x film on organic-based electronic devices, specifically, very high-frequency (162 MHz) plasma-enhanced chemical vapor deposition (VHF-PECVD) using a multi-tile push-pull plasma source with a gas mixture of NH 3 /SiH 4 at a low temperature of 80 °C. The thin deposited SiN x film exhibited excellent properties in the stoichiometry, chemical bonding, stress, and step coverage. Thin film quality and plasma damage were investigated by the water vapor transmission rate (WVTR) and by electrical characteristics of organic light-emitting diode (OLED) devices deposited with SiN x , respectively. The thin deposited SiN x film exhibited a low WVTR of 4.39 × 10 -4  g (m 2 · day) -1 for a single thin (430 nm thick) film SiN x and the electrical characteristics of OLED devices before and after the thin SiN x film deposition on the devices did not change, which indicated no electrical damage during the deposition of SiN x on the OLED device.

Measurement of sin2θefflept using e+e- pairs from γ*/Z bosons produced in p p ¯ collisions at a center-of-momentum energy of 1.96 TeV

NASA Astrophysics Data System (ADS)

Aaltonen, T.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Auerbach, B.; Aurisano, A.; Azfar, F.; Badgett, W.; Bae, T.; Barbaro-Galtieri, A.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartos, P.; Bauce, M.; Bedeschi, F.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Bhatti, A.; Bland, K. R.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brigliadori, L.; Bromberg, C.; Brucken, E.; Budagov, J.; Budd, H. S.; Burkett, K.; Busetto, G.; Bussey, P.; Butti, P.; Buzatu, A.; Calamba, A.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cerri, A.; Cerrito, L.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Chokheli, D.; Clark, A.; Clarke, C.; Convery, M. E.; Conway, J.; Corbo, M.; Cordelli, M.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; d'Ascenzo, N.; Datta, M.; de Barbaro, P.; Demortier, L.; Deninno, M.; D'Errico, M.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Dittmann, J. R.; Donati, S.; D'Onofrio, M.; Dorigo, M.; Driutti, A.; Ebina, K.; Edgar, R.; Erbacher, R.; Errede, S.; Esham, B.; Farrington, S.; Fernández Ramos, J. P.; Field, R.; Flanagan, G.; Forrest, R.; Franklin, M.; Freeman, J. C.; Frisch, H.; Funakoshi, Y.; Galloni, C.; Garfinkel, A. F.; Garosi, P.; Gerberich, H.; Gerchtein, E.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Giokaris, N.; Giromini, P.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grosso-Pilcher, C.; Guimaraes da Costa, J.; Hahn, S. R.; Han, J. Y.; Happacher, F.; Hara, K.; Hare, M.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hays, C.; Heinrich, J.; Herndon, M.; Hocker, A.; Hong, Z.; Hopkins, W.; Hou, S.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jang, D.; Jayatilaka, B.; Jeon, E. J.; Jindariani, S.; Jones, M.; Joo, K. K.; Jun, S. Y.; Junk, T. R.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Kasmi, A.; Kato, Y.; Ketchum, W.; Keung, J.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. H.; Kim, S. B.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kurata, M.; Laasanen, A. T.; Lammel, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lee, H. S.; Lee, J. S.; Leo, S.; Leone, S.; Lewis, J. D.; Limosani, A.; Lipeles, E.; Lister, A.; Liu, Q.; Liu, T.; Lockwitz, S.; Loginov, A.; Lucchesi, D.; Lucà, A.; Lueck, J.; Lujan, P.; Lukens, P.; Lungu, G.; Lys, J.; Lysak, R.; Madrak, R.; Maestro, P.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Marchese, L.; Margaroli, F.; Marino, P.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Mesropian, C.; Miao, T.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nakano, I.; Napier, A.; Nett, J.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Okusawa, T.; Orava, R.; Ortolan, L.; Pagliarone, C.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parker, W.; Pauletta, G.; Paulini, M.; Paus, C.; Phillips, T. J.; Piacentino, G.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pondrom, L.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ristori, L.; Robson, A.; Rodriguez, T.; Rolli, S.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sakumoto, W. K.; Sakurai, Y.; Santi, L.; Sato, K.; Saveliev, V.; Savoy-Navarro, A.; Schlabach, P.; Schmidt, E. E.; Schwarz, T.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Semenov, A.; Sforza, F.; Shalhout, S. Z.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simonenko, A.; Sliwa, K.; Smith, J. R.; Snider, F. D.; Song, H.; Sorin, V.; St. Denis, R.; Stancari, M.; Stentz, D.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Ukegawa, F.; Uozumi, S.; Vázquez, F.; Velev, G.; Vellidis, C.; Vernieri, C.; Vidal, M.; Vilar, R.; Vizán, J.; Vogel, M.; Volpi, G.; Wagner, P.; Wallny, R.; Wang, S. M.; Waters, D.; Wester, W. C.; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wolbers, S.; Wolfe, H.; Wright, T.; Wu, X.; Wu, Z.; Yamamoto, K.; Yamato, D.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W.-M.; Yeh, G. P.; Yi, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G. B.; Yu, I.; Zanetti, A. M.; Zeng, Y.; Zhou, C.; Zucchelli, S.; CDF Collaboration

2016-06-01

At the Fermilab Tevatron proton-antiproton (p p ¯) collider, Drell-Yan lepton pairs are produced in the process p p ¯→e+e-+X through an intermediate γ*/Z boson. The forward-backward asymmetry in the polar-angle distribution of the e- as a function of the e+e--pair mass is used to obtain sin2θefflept, the effective leptonic determination of the electroweak-mixing parameter sin2θW. The measurement sample, recorded by the Collider Detector at Fermilab (CDF), corresponds to 9.4 fb-1 of integrated luminosity from p p ¯ collisions at a center-of-momentum energy of 1.96 TeV, and is the full CDF Run II data set. The value of sin2θefflept is found to be 0.23248 ±0.00053 . The combination with the previous CDF measurement based on μ+μ- pairs yields sin2θefflept=0.23221±0.00046 . This result, when interpreted within the specified context of the standard model assuming sin2θW=1 - MW2/MZ2 and that the W - and Z -boson masses are on-shell, yields sin2θW=0.22400 ±0.00045 , or equivalently a W -boson mass of 80.328 ±0.024 GeV /c2 .

Ultralow power switching in a silicon-rich SiNy/SiNx double-layer resistive memory device.

PubMed

Kim, Sungjun; Chang, Yao-Feng; Kim, Min-Hwi; Bang, Suhyun; Kim, Tae-Hyeon; Chen, Ying-Chen; Lee, Jong-Ho; Park, Byung-Gook

2017-07-26

Here we demonstrate low-power resistive switching in a Ni/SiN y /SiN x /p ++ -Si device by proposing a double-layered structure (SiN y /SiN x ), where the two SiN layers have different trap densities. The LRS was measured to be as low as 1 nA at a voltage of 1 V, because the SiN x layer maintains insulating properties for the LRS. The single-layered device suffers from uncontrollability of the conducting path, accompanied by the inherent randomness of switching parameters, weak immunity to breakdown during the reset process, and a high operating current. On the other hand, for a double-layered device, the effective conducting path in each layer, which can determine the operating current, can be well controlled by the I CC during the initial forming and set processes. A one-step forming and progressive reset process is observed for a low-power mode, which differs from the high-power switching mode that shows a two-step forming and reset process. Moreover, nonlinear behavior in the LRS, whose origin can be attributed to the P-F conduction and F-N tunneling driven by abundant traps in the silicon-rich SiN x layer, would be beneficial for next-generation nonvolatile memory applications by using a conventional passive SiN x layer as an active dielectric.

Stress engineering in GaN structures grown on Si(111) substrates by SiN masking layer application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szymański, Tomasz, E-mail: tomasz.szymanski@pwr.edu.pl; Wośko, Mateusz; Paszkiewicz, Bogdan

2015-07-15

GaN layers without and with an in-situ SiN mask were grown by using metal organic vapor phase epitaxy for three different approaches used in GaN on silicon(111) growth, and the physical and optical properties of the GaN layers were studied. For each approach applied, GaN layers of 1.4 μm total thickness were grown, using silan SiH{sub 4} as Si source in order to grow Si{sub x}N{sub x} masking layer. The optical micrographs, scanning electron microscope images, and atomic force microscope images of the grown samples revealed cracks for samples without SiN mask, and micropits, which were characteristic for the samples grownmore » with SiN mask. In situ reflectance signal traces were studied showing a decrease of layer coalescence time and higher degree of 3D growth mode for samples with SiN masking layer. Stress measurements were conducted by two methods—by recording micro-Raman spectra and ex-situ curvature radius measurement—additionally PLs spectra were obtained revealing blueshift of PL peak positions with increasing stress. The authors have shown that a SiN mask significantly improves physical and optical properties of GaN multilayer systems reducing stress in comparison to samples grown applying the same approaches but without SiN masking layer.« less

Magnetic heading reference

NASA Technical Reports Server (NTRS)

Garner, H. D. (Inventor)

1983-01-01

Devices are disclosed for vectorially summing two signals. In a first embodiment, the vectorial summation is implemented by a mechanical sin/cos mechanism in which a crank drives two linear potentiometers out of phase. In a second embodiment, a polarized light resolver generates the sin and cos functions. In a third embodiment, a printed circuit resolver generates the sin and cos functions.

Quantifying benefits and risks of vaccinating Australian children aged six months to four years with trivalent inactivated seasonal influenza vaccine in 2010.

PubMed

Kelly, H; Carcione, D; Dowse, G; Effler, P

2010-09-16

Australian and New Zealand health authorities identified seasonal trivalent inactivated influenza vaccines manufactured by CSL Biotherapies as the probable cause of increased febrile convulsions in children under five within 24 hours of vaccination and recommended against their use in this age group. We quantified the benefit-risk profile of the CSL vaccines using the number needed to vaccinate and suggest they might have caused two to three hospital admissions due to febrile convulsions for every hospital admission due to influenza prevented.

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2010-10-01

count < 15,000 > 7 days or need for > 3 plt transfusions in 30 days • Gr 4 neutropenia > 7 days • Febrile neutropenia • Attributable Gr > 3...11% No febrile neutropenia (no growth factor use) • Transaminitis Transient Gr 1 AST 29% (1 Gr 2) Need for transfusions 6 pts...No pts had significant bleeding; 2 received plt transfusions (cohort 6) • Neutropenia Gr 0 = 40%; Gr 1-2 = 32%; Gr 3 = 29%; Gr 4

A Performance and Plume Comparison of Xenon and Krypton Propellant on the SPT-100

DTIC Science & Technology

2012-07-20

2 2 )sin()cos()()( )cos(     dvmr vmT mvm      dvvf vdvvf v )( )(     2/ 2/ 2 2/ 2/ 2 )sin()( )sin()()(       dmr

Constructing a Counternarrative: Students Informing Now (S.I.N.) Reframes Immigration and Education in the United States

ERIC Educational Resources Information Center

Dominguez, Neidi; Duarte, Yazmin; Espinosa, Pedro Joel; Martinez, Luis; Nygreen, Kysa; Perez, Renato; Ramirez, Izel; Saba, Mariella

2009-01-01

The work of Students Informing Now (S.I.N.), an immigrant student organization at the University of California, Santa Cruz, is described in this column. The authors argue that S.I.N.'s diverse activities and textual products construct a counternarrative that challenges and reframes the debate on undocumented students and immigration. Focusing on…

New Spectroscopic Solution of the Eclipsing Binary HX Vel A

NASA Astrophysics Data System (ADS)

Sürgit, D.; Erdem, A.; Özkardeş, B.; Butland, R.; Budding, E.

2015-07-01

We present a preliminary analysis of new spectroscopic observations of the southern binary HX Vel A. High-resolution spectroscopic observations were made at the Mt. John University Observatory in 2014. Radial velocities for HX Vel A were determined from the Gaussian profile-fitting method. The Keplerian radial velocity model gives the close binary mass ratio as 0.57±0.06. The resulting orbital elements are a1sin i=0.0086 ±0.0003 au, a2sin i=0.0151 ±0.0003 au, M1 sin3i =0.887 ±0.046 M⊙, and M2 sin3i =0.504 ±0.032 M⊙.

Strategies to alleviate original antigenic sin responses to influenza viruses.

PubMed

Kim, Jin Hyang; Davis, William G; Sambhara, Suryaprakash; Jacob, Joshy

2012-08-21

Original antigenic sin is a phenomenon wherein sequential exposure to closely related influenza virus variants reduces antibody (Ab) response to novel antigenic determinants in the second strain and, consequently, impairs the development of immune memory. This could pose a risk to the development of immune memory in persons previously infected with or vaccinated against influenza. Here, we explored strategies to overcome original antigenic sin responses in mice sequentially exposed to two closely related hemagglutinin 1 neuraminidase 1 (H1N1) influenza strains A/PR/8/34 and A/FM/1/47. We found that dendritic cell-activating adjuvants [Bordetella pertussis toxin (PT) or CpG ODN or a squalene-based oil-in-water nanoemulsion (NE)], upon administration during the second viral exposure, completely protected mice from a lethal challenge and enhanced neutralizing-Ab titers against the second virus. Interestingly, PT and NE adjuvants when administered during the first immunization even prevented original antigenic sin in subsequent immunization without any adjuvants. As an alternative to using adjuvants, we also found that repeated immunization with the second viral strain relieved the effects of original antigenic sin. Taken together, our studies provide at least three ways of overcoming original antigenic sin.

Influence of barrier absorption properties on laser patterning thin organic films

NASA Astrophysics Data System (ADS)

Naithani, Sanjeev; Mandamparambil, Rajesh; van Assche, Ferdie; Schaubroeck, David; Fledderus, Henri; Prenen, An; Van Steenberge, Geert; Vanfleteren, Jan

2012-06-01

This paper presents a study of selective ablation of thin organic films (LEP- Light Emitting Polymer, PEDOT:PSS- Poly 3,4-ethylenedioxythiophene: polystyrene sulfonate) by using 248 nm Excimer laser, on various kinds of multilayered SiN barrier foils for the development of Organic Light Emitting Diodes (OLED). Different Silicon Nitride (SiN) barrier foils with dedicated absorption spectra are taken into account for this purpose. The drive for looking into different types of SiN originates from the fact that the laser selective removal of a polymer without damage to the barrier layer underneath is challenging in the dynamic laser processing of thin films. The barrier is solely responsible for the proper encapsulation of the OLED stack. The main limitation of current OLED design is its shorter life span, which is directly related to the moisture or water permeation into the stack, leading to black spots. An optimization of laser parameters like fluence and number of shots has been carried out for the various types of SiN barrier foils. We are able to obtain a wider working process window for the selective removal of LEP and PEDOT:PSS from SiN barrier, by variation of the different types of SiN.

Fixed interface charges between AlGaN barrier and gate stack composed of in situ grown SiN and Al{sub 2}O{sub 3} in AlGaN/GaN high electron mobility transistors with normally off capability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capriotti, M., E-mail: mattia.capriotti@tuwien.ac.at; Alexewicz, A.; Fleury, C.

2014-03-17

Using a generalized extraction method, the fixed charge density N{sub int} at the interface between in situ deposited SiN and 5 nm thick AlGaN barrier is evaluated by measurements of threshold voltage V{sub th} of an AlGaN/GaN metal insulator semiconductor high electron mobility transistor as a function of SiN thickness. The thickness of the originally deposited 50 nm thick SiN layer is reduced by dry etching. The extracted N{sub int} is in the order of the AlGaN polarization charge density. The total removal of the in situ SiN cap leads to a complete depletion of the channel region resulting in V{sub th} = +1 V.more » Fabrication of a gate stack with Al{sub 2}O{sub 3} as a second cap layer, deposited on top of the in situ SiN, is not introducing additional fixed charges at the SiN/Al{sub 2}O{sub 3} interface.« less

Associations of Initial Society for Fetal Urology Grades and Urinary Tract Dilatation Risk Groups with Clinical Outcomes in Patients with Isolated Prenatal Hydronephrosis.

PubMed

Braga, Luis H; McGrath, Melissa; Farrokhyar, Forough; Jegatheeswaran, Kizanee; Lorenzo, Armando J

2017-03-01

There are limited comparative data on the predictive value of the 2 most commonly used classification systems, that is SFU (Society for Fetal Urology) hydronephrosis grades and urinary tract dilatation risk groups, in regard to the future risk of surgical intervention and the development of febrile urinary tract infection. We explored this topic in infants with isolated hydronephrosis. After screening 938 patients with prenatal hydronephrosis from 2009 to 2016 we selected 322 patients with ureteropelvic junction obstruction-like hydronephrosis for study. Hydronephrosis grades were prospectively collected at baseline, surgery and last followup. Gender, circumcision status, antibiotic prophylaxis and renal pelvis anteroposterior diameter were captured. The primary outcome was pyeloplasty and the development of febrile urinary tract infection. Comparative analyses between SFU grades/urinary tract dilatation groups and the primary outcome were performed with the Fisher exact and log rank tests. Mean ± SD age at presentation was 3.3 ± 2.6 months and mean followup was 22 ± 19 months. Pyeloplasty was performed in 32% of patients with SFU III/IV vs 31% with urinary tract dilatation 2/3. The rate of febrile urinary tract infection in patients with SFU III/IV was similar to that in those with urinary tract dilatation group 2/3 (8% vs 10%). Children with SFU III/IV showed a significantly higher rate of surgery than those with SFU I/II (32% vs 2%, p <0.01). Similar findings were seen when using urinary tract dilatation groups to compare patients at low risk (1) vs moderate/high risk (2/3). Both grading systems equally allowed for proper risk stratification and prediction of clinical outcomes based on baseline ultrasound. They correctly separated most infants who underwent surgery or in whom febrile urinary tract infection developed from those who could be treated nonsurgically. Use of the new urinary tract dilatation classification should not affect how families of children with isolated hydronephrosis are counseled regarding surgical intervention and the risk of febrile urinary tract infection. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bayesian Latent Class Models in Malaria Diagnosis

PubMed Central

Gonçalves, Luzia; Subtil, Ana; de Oliveira, M. Rosário; do Rosário, Virgílio; Lee, Pei-Wen; Shaio, Men-Fang

2012-01-01

Aims The main focus of this study is to illustrate the importance of the statistical analysis in the evaluation of the accuracy of malaria diagnostic tests, without admitting a reference test, exploring a dataset (3317) collected in São Tomé and Príncipe. Methods Bayesian Latent Class Models (without and with constraints) are used to estimate the malaria infection prevalence, together with sensitivities, specificities, and predictive values of three diagnostic tests (RDT, Microscopy and PCR), in four subpopulations simultaneously based on a stratified analysis by age groups (, 5 years old) and fever status (febrile, afebrile). Results In the afebrile individuals with at least five years old, the posterior mean of the malaria infection prevalence is 3.2% with a highest posterior density interval of [2.3–4.1]. The other three subpopulations (febrile 5 years, afebrile or febrile children less than 5 years) present a higher prevalence around 10.3% [8.8–11.7]. In afebrile children under-five years old, the sensitivity of microscopy is 50.5% [37.7–63.2]. In children under-five, the estimated sensitivities/specificities of RDT are 95.4% [90.3–99.5]/93.8% [91.6–96.0] – afebrile – and 94.1% [87.5–99.4]/97.5% [95.5–99.3] – febrile. In individuals with at least five years old are 96.0% [91.5–99.7]/98.7% [98.1–99.2] – afebrile – and 97.9% [95.3–99.8]/97.7% [96.6–98.6] – febrile. The PCR yields the most reliable results in four subpopulations. Conclusions The utility of this RDT in the field seems to be relevant. However, in all subpopulations, data provide enough evidence to suggest caution with the positive predictive values of the RDT. Microscopy has poor sensitivity compared to the other tests, particularly, in the afebrile children less than 5 years. This type of findings reveals the danger of statistical analysis based on microscopy as a reference test. Bayesian Latent Class Models provide a powerful tool to evaluate malaria diagnostic tests, taking into account different groups of interest. PMID:22844405

Response to fever and utilization of standby emergency treatment (SBET) for malaria in travellers to Southeast Asia: a questionnaire-based cohort study.

PubMed

Vinnemeier, Christof D; Rothe, Camilla; Kreuels, Benno; Addo, Marylyn M; Vygen-Bonnet, Sabine; Cramer, Jakob P; Rolling, Thierry

2017-01-25

Guidelines in several European countries recommend standby emergency treatment (SBET) for travellers to regions with low or medium malaria transmission instead of continuous chemoprophylaxis: travellers are advised to seek medical assistance within 24 h in case of fever and to self-administer SBET only if they are not able to consult a doctor within the time period specified. Data on healthcare-seeking behaviour of febrile travellers and utilization of SBET is however scarce as only two studies were performed in the mid-1990s. Since tourism is constantly increasing and malaria epidemiology has dramatically changed in the meantime more knowledge is urgently needed. Some 876 travellers to destinations in South and Southeast Asia with low or medium malaria transmission were recruited in the travel clinic of the University Medical Center Hamburg-Eppendorf. Demographic and travel-related data were collected by using questionnaires. Pre-travel advice was carried out and SBET was prescribed in accordance to national guidelines. Post-travel phone interviews were performed to assess health incidents during travel and individual responses of travellers to febrile illness. Out of 714 patients who were monitored, 130 (18%) reported onset of fever during travel or 14 days after return. Of those travellers who reported fever, 100 (80%) carried SBET during travel. The vast majority of 79 (79%) febrile travellers who carried SBET did not seek medical assistance. Overall, 14 (14%) febrile patients who carried SBET and six (20%) patients who did not carry SBET took the correct measure (doctor visit or timely SBET administration) as a response to febrile illness, respectively. Only two travellers self-administered SBET, but both of them applied the wrong regimen. In view of declining malaria transmission and improving medical infrastructure in most countries of Southeast Asia and obvious obstacles concerning SBET as shown in this study the current strategy should be re-evaluated. Pre-travel advice concerning malaria in SEA should focus on appropriate mosquito bite protection and clearly emphasize the need to see a doctor within 24 h after onset of fever.

Recommendations for the inclusion of Fabry disease as a rare febrile condition in existing algorithms for fever of unknown origin.

PubMed

Manna, Raffaele; Cauda, Roberto; Feriozzi, Sandro; Gambaro, Giovanni; Gasbarrini, Antonio; Lacombe, Didier; Livneh, Avi; Martini, Alberto; Ozdogan, Huri; Pisani, Antonio; Riccio, Eleonora; Verrecchia, Elena; Dagna, Lorenzo

2017-10-01

Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.

Can procalcitonin reduce unnecessary voiding cystoureterography in children with first febrile urinary tract infection?

PubMed

Halimi-Asl, Aliasghar; Hosseini, Amir Hossein; Nabavizadeh, Pooneh

2014-08-01

Recently, new predictors of vesicoureteral reflux (VUR) in children with a first febrile UTI such as Procalcitonin (PCT) were introduced as selective approaches for cystography. This study wants to show the capability of PCT in predicting presence of VUR at the first febrile UTI in children. Patients between 1 month and 15 years of age with febrile UTI were included in this prospective study. PCT values were measured through a semi-quantitative method in four grades comprising values less than 0.5, 0.5-2.0, 2.0-10.0 and above 10.0 ng/ml. The independence of PCT levels in predicting VUR were assessed after adjustment for all potential confounders using a logistic-regression model. A total of 68 patients, 54 (79.4%) girls and 14 (20.6%) boys were evaluated. PCT level demonstrated a significant difference between patients with positive VUR and those with negative VUR (P=0.012). To calculate the independent factors that may predict the presence of VUR, all included variables were adjusted for age and sex. Results of logistic regression showed that a PCT level between 2.0 and 10.0 ng/mL could independently predict presence of VUR (Odds ratio=6.11, CI 95%= 1.22-30.77, P=0.03). Our finding in this study showed that readily available semi-quantitative measures for PCT are feasible for detecting patients with VUR. We suggest that in semi-quantitative measurements of PCT, levels between 2.0 and 10.0 ng/ml could be an independent predictor of positive VUR.

Prevalence and risk factors for encephalomyocarditis virus infection in Peru.

PubMed

Czechowicz, Josephine; Huaman, Jose Luis; Forshey, Brett M; Morrison, Amy C; Castillo, Roger; Huaman, Alfredo; Caceda, Roxana; Eza, Dominique; Rocha, Claudio; Blair, Patrick J; Olson, James G; Kochel, Tadeusz J

2011-04-01

Although encephalomyocarditis virus (EMCV) infection has been commonly documented among domestic animals, less is known about EMCV transmission among humans. Recently, we described the isolation of EMCV from two febrile patients in Peru. To further investigate EMCV transmission in Peru, we screened febrile patients reporting to health clinics in Peru for serological evidence of recent EMCV infection. We also conducted a serological survey for EMCV-neutralizing antibodies in the city of Iquitos, located in the Amazon basin department of Loreto, Peru. Additionally, we screened serum from rodents collected from 10 departments in Peru for evidence of EMCV exposure. EMCV infection was found to be only rarely associated with acute febrile disease in Peru, accounting for <1% of febrile episodes analyzed. Despite the low acute disease burden associated with the virus, human exposure was quite common, as prevalence of EMCV-neutralizing antibodies ranged between 6.0% in the coastal city of Tumbes and >17% in cities in the tropical rainforest of northeastern Peru (Iquitos and Yurimaguas). On the basis of the serological survey conducted in Iquitos, risk factors for past infection include increased age, socioeconomic indicators such as residence construction materials and neighborhood, and swine ownership. Evidence from the rodent survey indicates that EMCV exposure is common among Murinae subfamily rodents in Peru (9.4% EMCV IgG positive), but less common among Sigmodontinae rodents (1.0% positive). Further studies are necessary to more precisely delineate the mode of EMCV transmission to humans, other potential disease manifestations, and the economic impact of EMCV transmission among swine in Peru.

Midazolam fails to prevent neurological damage in children with convulsive refractory febrile status epilepticus.

PubMed

Nagase, Hiroaki; Nishiyama, Masahiro; Nakagawa, Taku; Fujita, Kyoko; Saji, Yohsuke; Maruyama, Azusa

2014-07-01

We conducted a retrospective study to compare the outcome of intravenous midazolam infusion without electroencephalography or targeted temperature management and barbiturate coma therapy with electroencephalography and targeted temperature management for treating convulsive refractory febrile status epilepticus. Of 49 consecutive convulsive refractory febrile status epilepticus patients admitted to the pediatric intensive care unit of our hospital, 29 were excluded because they received other treatments or because of various underlying illnesses. Thus, eight patients were treated with midazolam and 10 with barbiturate coma therapy using thiamylal. Midazolam-treated patients were intubated only when necessary, whereas barbiturate coma therapy patients were routinely intubated. Continuous electroencephalography monitoring was utilized only for the barbiturate coma group. The titration goal for anesthesia was clinical termination of status epilepticus in the midazolam group and suppression or burst-suppression patterns on electroencephalography in the barbiturate coma group. Normothermia was maintained using blankets and neuromuscular blockade in the barbiturate coma group and using antipyretics in the midazolam group. Prognoses were measured at 1 month after onset; children were classified into poor and good outcome groups. Good outcome was achieved in all the barbiturate coma group patients and 50% of the midazolam group patients (P = 0.02, Fisher's exact test). Although the sample size was small and our study could not determine which protocol element is essential for the neurological outcome, the findings suggest that clinical seizure control using midazolam without continuous electroencephalography monitoring or targeted temperature management is insufficient in preventing neurological damage in children with convulsive refractory febrile status epilepticus. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevalence of and risk factors for symptomatic urinary tract infection after endoscopic incision for the treatment of ureterocele in children.

PubMed

Moriya, Kimihiko; Nakamura, Michiko; Nishimura, Yoko; Kanno, Yukiko; Kitta, Takeya; Kon, Masafumi; Shinohara, Nobuo

2017-09-01

To clarify the impact of endoscopic incision (EI) for ureterocele as an initial procedure, by performing a retrospective chart review, focusing on the prevalence of and risk factors for symptomatic urinary tract infection (UTI) after EI. In the present study we included children with ureterocele, managed between September 1994 and April 2016, who were observed conservatively without additional surgical management after EI. Ureterocele was categorized as intravesical or ectopic. Symptomatic UTI was defined as either recurrent non-febrile or febrile UTI. The prevalence of and risk factors for symptomatic UTI were analysed using Cox proportional hazard models or Kaplan-Meier curves, and the log-rank test. A total of 36 children met the inclusion criteria. The median age of the participants at EI was 8.9 months. Eleven children had symptomatic UTIs (febrile, n = 9; recurrent non-febrile, n = 2) during the median follow-up of 75.5 months. Initial symptomatic UTI in each child occurred <25 months after EI. The symptomatic UTI-free rate after EI was 65.6%. The risk factors for symptomatic UTI were female gender, duplex system, ectopic ureterocele, and unchanged hydronephrosis after EI. The present study determined the critical period and risk factors for symptomatic UTI after EI for the treatment of ureterocele. The results suggest that when conservative management is indicated after EI, patients, especially those with risk factors, should be followed carefully at least for 25 months after EI for symptomatic UTI. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Renal excretion of prostaglandin metabolites, arginine vasopressin, and sodium during endotoxin and endogenous pyrogen induced fever in the goat.

PubMed

Jónasson, H; Basu, S; Andersson, B; Kindahl, H

1984-04-01

Responses to intravenous injections of an endotoxin (E. coli-lipopolysaccharide, 1 microgram/kg b.wt.) and endogenous pyrogen were studied in euhydrated and hyperhydrated goats. The biphasic febrile response to the endotoxin was associated with a pronounced increase in the renal excretion of measured prostaglandin (PG) metabolites (11-ketotetranor PGF metabolites). This increase was time-correlated with the elevation of the rectal temperature, and (in hyperhydrated animals) with an inhibition of the water diuresis and an increase in renal excretion of arginine vasopressin (AVP). Other effects of the endotoxin were an immediate depression of renal Na and K excretion followed by the development of pronounced natriuresis, and a reduction of plasma Fe and Zn concentrations. The appearance of the febrile reactions (peripheral vasoconstriction and shivering) was accompanied by miosis. The maximum elevation of the rectal temperature was significantly greater during euhydration than during hyperhydration. Also endogenous pyrogen elicited miosis concomitant with febrile reactions, and an elevation of the renal excretion of PG metabolites which was closely correlated in time with the monophasic febrile response, and (during hyperhydration) with temporary inhibition of the water diuresis and an increase in the renal AVP excretion. However, the responses were much weaker than the corresponding endotoxin effects. No appreciable changes in renal excretion of Na and K were observed in response to the endogenous pyrogen. It is concluded that the observed effects on renal cation excretion were manifestations of direct endotoxin influences on kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of the variability in the febrile responses of rabbits to endogenous pyrogen.

PubMed

Stitt, J T

1985-10-01

The range of body temperature increases elicited by a standard dose of endogenous pyrogen (0.5 ml/kg iv) was examined in a population of 26 male New Zealand White rabbits. Although the mean maximum increase in rectal temperature was 0.88 +/- 0.06 degree C (SE), individual responses varied from 0.4 degree to 1.5 degree C. Three representative animals that responded to the standard dose of pyrogen with small, intermediate, and large febrile responses were selected and challenged with the same dose of pyrogen on eight separate occasions, and the variability of these responses was examined. There was little variability within the characteristic responses of any particular animal to the repeated challenges. The variability of the febrile responses elicited by both intravenous and intracerebroventricular administration of the same pyrogen was examined and compared using another group of 11 rabbits. The variability in response to the intravenous route was similar to that found in the larger population, whereas the variation in response to the intracerebroventricular route was smaller, and all 11 animals had fevers that were greater than 1 degrees C. It is concluded that the variability of the febrile responses of rabbits to intravenous pyrogen was due to differences between individual sensitivities of animals to the intravenously administered pyrogen. This difference in sensitivity may be due to a difference in the amount of pyrogen that reaches the putative receptor sites, or to a difference in the density or effectiveness of receptor sites in translating the pyrogenic stimulus into a fever response.

Incidence of respiratory viruses among travelers with a febrile syndrome returning from tropical and subtropical areas.

PubMed

Camps, M; Vilella, A; Marcos, M A; Letang, E; Muñoz, J; Salvadó, E; González, A; Gascón, J; Jiménez de Anta, M T; Pumarola, T

2008-04-01

Fifty million people are estimated to travel from industrial countries to the tropics annually. In spite of exhaustive studies and widely different diagnosis among returned patients, some cases of febrile illnesses remain without an etiological diagnosis, suggesting that these cases could be due to viral respiratory tract infections. From August 2005 to October 2006, 118 febrile patients without a specific diagnosis in their first visit at the Center for International Health of the Hospital Clínic of Barcelona were included. In all of them, in order to study respiratory viruses, a nasopharyngeal swab was collected. Clinical and radiological features and epidemiological data, as well as other samples for microbiologic studies, were also collected during consultation. Based on the physician's judgment at the time of consultation, patients were classified into four groups: respiratory symptoms (62%), febrile syndrome with nonspecific symptoms (24%), digestive symptoms (10%), and patients presenting both respiratory and digestive symptoms (4%). A pathogen microorganism was detected in 61 patients (52%). Respiratory viruses were detected in 44 out of 118 (37%) travelers included in the study, representing 56% of the patients with respiratory symptoms. The most frequently viruses detected were influenza virus (38%), rhinovirus (23%), adenovirus (9%), and respiratory syncytial virus (9%). Respiratory viruses have been shown to play an important role in imported fever. In light of the fact that international tourism is an increasing phenomenon, new strategies to prevent the spread of respiratory viruses should be considered, specially for influenza when a vaccine is available.

A clinical evaluation of efficacy and safety of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia in a tertiary care centre of north India.

PubMed

Aamir, Mohammad; Abrol, Pankaj; Sharma, Deepak; Punia, Harish

2016-07-01

To evaluate clinically the efficacy and safety in northern India of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia. Children aged ≤18 years admitted febrile with chemotherapy-induced neutropenia were randomised into two groups comprising 20 cases in each group viz. CEF (receiving cefepime only) and PIP-TAZO (receiving piperacillin-tazobactam). Based on clinical and laboratory tests, patients were classified into: microbiologically documented infections (MDI); clinically documented infections (CDI); and unexplained fever (UF). They were assessed for clinical signs and symptoms as well as laboratory parameters at the time of enrolment and subsequently on days 3 and 7. Incidence of MDI, CDI and UF were 22.5%, 47.5% and 30%, respectively. The mean duration of neutropenia (in days) was 5.45 ± 2.1 in the PIP-TAZO group and 5.5 ± 1.5 in the CEF group (P = 0.305). The success rate defined as clearing infection effectively and improvement of neutropenia was comparable (P = 0.705). There was a mortality rate of 20% in the PIP-TAZO group as compared to 10% in the CEF group. We conclude that cefepime monotherapy and piperacillin-tazobactam are equally efficacious and safe in treating patients with febrile neutropenia. Empirical monotherapy with cefepime would prevent an unnecessary extra economic burden as well as avoiding the serious adverse or toxic effects of multi-drug regimes, especially in low- and middle-income countries. © The Author(s) 2015.

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

PubMed

Gerritsen, M G; Willemink, M J; Pompe, E; van der Bruggen, T; van Rhenen, A; Lammers, J W J; Wessels, F; Sprengers, R W; de Jong, P A; Minnema, M C

2017-01-01

We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia

PubMed Central

Averbuch, Diana; Orasch, Christina; Cordonnier, Catherine; Livermore, David M.; Mikulska, Małgorzata; Viscoli, Claudio; Gyssens, Inge C.; Kern, Winfried V.; Klyasova, Galina; Marchetti, Oscar; Engelhard, Dan; Akova, Murat

2013-01-01

Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4th European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient’s risk factors for resistant bacteria and for a complicated clinical course. An ‘escalation’ approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A ‘de-escalation’ approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72–96 h should be based on the patient’s clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance. PMID:24323983

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography

PubMed Central

Pompe, E.; van der Bruggen, T.; van Rhenen, A.; Lammers, J. W. J.; Wessels, F.; Sprengers, R. W.; de Jong, P. A.; Minnema, M. C.

2017-01-01

We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose. PMID:28235014

Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

PubMed

McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

2018-04-25

Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

Empirical first-line treatment with tigecycline for febrile episodes following abdominal surgery in cancer patients.

PubMed

Secondo, Giovanni; Vassallo, Francesca; Solari, Nicola; Moresco, Luciano; Percivale, Pierluigi; Zappi, Lucia; Cafiero, Ferdinando; De Maria, Andrea

2010-11-01

Cancer patients with complicated infections following abdominal surgery represent one of the worst clinical scenarios that is useful for testing the efficacy of empirical antimicrobial therapy. No study so far has evaluated the performance of tigecycline (TIG) when administered as empirical first-line treatment in a homogeneous population of surgical cancer patients with a febrile episode. An observational review of the data records of 24 sequential patients receiving TIG for a febrile episode following a major abdominal procedure in a single cancer institute was performed. Large bowel surgery represented 68% of all procedures, followed by gastric surgery (16%) and urinary-gynaecologic-biliary surgery (16%). Complications following surgery were observed in 68% of febrile episodes, with peritonitis and sepsis accounting for 59% and 24% of complications, respectively. Eight patients needed repeat surgery for source control. The mean duration of TIG treatment was 8 days. Causative pathogens were detected in 16 episodes (64%), and a total of 44 microorganisms were recovered (29% Escherichia coli, 9% Enterococcus faecalis and 9% coagulase-negative staphylococci). TIG was effective in 12 episodes (48%). The success rate was 67% when infectious episodes sustained by intrinsically resistant bacteria and fungi were excluded. Treatment failure was associated with the presence of complications and with microbiologically documented infection. TIG may be useful as a first-line treatment option in cancer patients requiring antibiotic treatment following surgery when complications are not present or suspected on clinical grounds and when local microbial epidemiology shows a low incidence of primary resistant bacteria. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Low-temperature SiON films deposited by plasma-enhanced atomic layer deposition method using activated silicon precursor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suh, Sungin; Kim, Jun-Rae; Kim, Seongkyung

2016-01-15

It has not been an easy task to deposit SiN at low temperature by conventional plasma-enhanced atomic layer deposition (PE-ALD) since Si organic precursors generally have high activation energy for adsorption of the Si atoms on the Si-N networks. In this work, in order to achieve successful deposition of SiN film at low temperature, the plasma processing steps in the PE-ALD have been modified for easier activation of Si precursors. In this modification, the efficiency of chemisorption of Si precursor has been improved by additional plasma steps after purging of the Si precursor. As the result, the SiN films preparedmore » by the modified PE-ALD processes demonstrated higher purity of Si and N atoms with unwanted impurities such as C and O having below 10 at. % and Si-rich films could be formed consequently. Also, a very high step coverage ratio of 97% was obtained. Furthermore, the process-optimized SiN film showed a permissible charge-trapping capability with a wide memory window of 3.1 V when a capacitor structure was fabricated and measured with an insertion of the SiN film as the charge-trap layer. The modified PE-ALD process using the activated Si precursor would be one of the most practical and promising solutions for SiN deposition with lower thermal budget and higher cost-effectiveness.« less

Lineage-specific SoxR-mediated Regulation of an Endoribonuclease Protects Non-enteric Bacteria from Redox-active Compounds*

PubMed Central

Kim, Jisun; Park, Chulwoo; Imlay, James A.; Park, Woojun

2017-01-01

Bacteria use redox-sensitive transcription factors to coordinate responses to redox stress. The [2Fe-2S] cluster-containing transcription factor SoxR is particularly tuned to protect cells against redox-active compounds (RACs). In enteric bacteria, SoxR is paired with a second transcription factor, SoxS, that activates downstream effectors. However, SoxS is absent in non-enteric bacteria, raising questions as to how SoxR functions. Here, we first show that SoxR of Acinetobacter oleivorans displayed similar activation profiles in response to RACs as did its homolog from Escherichia coli but controlled a different set of target genes, including sinE, which encodes an endoribonuclease. Expression, gel mobility shift, and mutational analyses indicated that sinE is a direct target of SoxR. Redox potentials and permeability of RACs determined optimal sinE induction. Bioinformatics suggested that only a few γ- and β-proteobacteria might have SoxR-regulated sinE. Purified SinE, in the presence of Mg2+ ions, degrades rRNAs, thus inhibiting protein synthesis. Similarly, pretreatment of cells with RACs demonstrated a role for SinE in promoting persistence in the presence of antibiotics that inhibit protein synthesis. Our data improve our understanding of the physiology of soil microorganisms by suggesting that both non-enteric SoxR and its target SinE play protective roles in the presence of RACs and antibiotics. PMID:27895125

Development and preliminary validation of a measure of social inclusion for use in people with mental health problems: the SInQUE.

PubMed

Mezey, Gillian; White, Sarah; Thachil, Ajoy; Berg, Rachel; Kallumparam, Sen; Nasiruddin, Omar; Wright, Christine; Killaspy, Helen

2013-08-01

Social exclusion can be both a cause and a consequence of mental health problems. Socially inclusive practice by mental health professionals can mitigate against the stigmatizing and excluding effects of severe mental illness. To develop and test the validity of a measure of social inclusion for individuals with severe mental illness - the Social Inclusion Questionnaire User Experience (SInQUE). The domains of the SInQUE were chosen to reflect the domains of social inclusion identified in the Poverty and Social Exclusion Survey. Patients with severe mental illness were recruited from rehabilitation, general and forensic psychiatric services and were asked to complete the questionnaire in an individual interview with a researcher. Sixty six patients with schizophrenia and schizoaffective disorder completed the SInQUE, alongside measures of psychiatric symptoms, needs and quality of life, to assess its acceptability, and concurrent and construct (convergent and discriminant) validity. The SInQUE took 45 minutes to complete and was found to have good concurrent and discriminant validity. Convergent validity was established for two domains: social integration and productivity. Preliminary findings suggest that the SInQUE may be a useful tool for assessing and monitoring social inclusion in individuals with severe mental illness. It has construct and concurrent validity with measures of unmet need and quality of life in this group. Further testing of the reliability of the SInQUE on a larger population is indicated.

Role of Fluorine-18-Fluorodeoxyglucose in the Work-up of Febrile AIDS Patients. Experience with Dual Head Coincidence Imaging.

PubMed

Santiago, Jonas F.; Jana, Suman; Gilbert, Holly M.; Salem, Shahenda; Bellman, Paul Curtis; Hsu, Ricky K.S.; Naddaf, Sleiman; Abdel-Dayem, Hussein M.

1999-11-01

OBJECTIVE AND METHODS: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.RESULTS: Our data show good sensitivity for scanning with F18-FDG by DHCI in determining the extent of Castleman's disease, lymphoma, Kaposi's sarcoma (KS), adenocarcinoma, and germ cell carcinoma. Various opportunistic infections also manifest with increased F18-FDG uptake.CONCLUSION: Total-body imaging can be done with F18-FDG with better resolution and a shorter procedure time compared to imaging with Gallium-67 (Ga-67). Furthermore, F18-FDG is more sensitive than Ga-67 for evaluating extent of involvement in various pathologies affecting AIDS patients. The new technology of DHCI is a good alternative for hospitals with no dedicated positron emission tomography (PET) scanner.

Febrile Illness with Skin Rashes

PubMed Central

2015-01-01

Skin rashes that appear during febrile illnesses are in fact caused by various infectious diseases. Since infectious exanthematous diseases range from mild infections that disappear naturally to severe infectious diseases, focus on and basic knowledge of these diseases is very important. But, these include non-infectious diseases, so that comprehensive knowledge of these other diseases is required. Usually, early diagnostic testing for a febrile illness with a rash is inefficient. For clinical diagnosis of diseases accompanied by skin rash and fever, a complete history must be taken, including recent travel, contact with animals, medications, and exposure to forests and other natural environments. In addition, time of onset of symptoms and the characteristics of the rash itself (morphology, location, distribution) could be helpful in the clinical diagnosis. It is also critical to understand the patient's history of specific underlying diseases. However, diagnostic basic tests could be helpful in diagnosis if they are repeated and the clinical course is monitored. Generally, skin rashes are nonspecific and self-limited. Therefore, it could be clinically meaningful as a characteristic diagnostic finding in a very small subset of specific diseases. PMID:26483989

Low risk of perioperative infection without prophylactic antibiotics for transperineal prostate brachytherapy.

PubMed

Wallner, K; Roy, J; Harrison, L

1996-10-01

To determine the incidence of postimplant infection in patients who are not given prophylactic antibiotics (ATBs). One hundred thirty-one patients had computerized tomography (CT)-planned transperineal 125I implantation of the prostate from 1988 through 1995. One hundred fourteen of the patients did not receive prophylactic ATBs, 19 of whom required postimplant Foley catheter drainage for 1 day or more for acute urinary retention. The incidence of postimplant febrile episodes within 2 weeks of surgery among the patients who had not received prophylactic ATBs was 2 of 114 (2%). One of the two patients who developed postimplantation febrile episodes was treated successfully with ATBs as an outpatient. The second patient, who had a history of chronic lymphocytic leukemia (CLL) and immune suppression, developed E. coli sepsis and required intravenous antibiotics. Of 17 patients who received prophylactic ATBs, none had a postoperative febrile episode. We continue to refrain from routinely prescribing prophylactic ATBs unless there is some compelling circumstance including rheumatic heart disease, prosthetic devices, immune compromise, or a previous history of prostatitis.

The automated analysis of clustering behaviour of piglets from thermal images in response to immune challenge by vaccination.

PubMed

Cook, N J; Bench, C J; Liu, T; Chabot, B; Schaefer, A L

2018-01-01

An automated method of estimating the spatial distribution of piglets within a pen was used to assess huddling behaviour under normal conditions and during a febrile response to vaccination. The automated method was compared with a manual assessment of clustering activity. Huddling behaviour was partly related to environmental conditions and clock time such that more huddling occurred during the night and at lower ambient air temperatures. There were no positive relationships between maximum pig temperatures and environmental conditions, suggesting that the narrow range of air temperatures in this study was not a significant factor for pig temperature. Spatial distribution affected radiated pig temperature measurements by IR thermography. Higher temperatures were recorded in groups of animals displaying huddling behaviour. Huddling behaviour was affected by febrile responses to vaccination with increased huddling occurring 3 to 8 h post-vaccination. The automated method of assessing spatial distribution from an IR image successfully identified periods of huddling associated with a febrile response, and to changing environmental temperatures. Infrared imaging could be used to quantify temperature and behaviour from the same images.

The time has come for new models in febrile neutropenia: a practical demonstration of the inadequacy of the MASCC score.

PubMed

Carmona-Bayonas, A; Jiménez-Fonseca, P; Virizuela Echaburu, J; Sánchez Cánovas, M; Ayala de la Peña, F

2017-09-01

Since its publication more than 15 years ago, the MASCC score has been internationally validated any number of times and recommended by most clinical practice guidelines for the management of febrile neutropenia (FN) around the world. We have used an empirical data-supported simulated scenario to demonstrate that, despite everything, the MASCC score is impractical as a basis for decision-making. A detailed analysis of reasons supporting the clinical irrelevance of this model is performed. First, seven of its eight variables are "innocent bystanders" that contribute little to selecting low-risk candidates for ambulatory management. Secondly, the training series was hardly representative of outpatients with solid tumors and low-risk FN. Finally, the simultaneous inclusion of key variables both in the model and in the outcome explains its successful validation in various series of patients. Alternative methods of prognostic classification, such as the Clinical Index of Stable Febrile Neutropenia, have been specifically validated for patients with solid tumors and should replace the MASCC model in situations of clinical uncertainty.

Challenges of establishing the correct diagnosis of outbreaks of acute febrile illnesses in Africa: the case of a likely Brucella outbreak among nomadic pastoralists, northeast Kenya, March-July 2005.

PubMed

Ari, Mary D; Guracha, Argata; Fadeel, Moustafa Abdel; Njuguna, Charles; Njenga, M Kariuki; Kalani, Rosalia; Abdi, Hassan; Warfu, Osman; Omballa, Victor; Tetteh, Christopher; Breiman, Robert F; Pimentel, Guillermo; Feikin, Daniel R

2011-11-01

An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed.

Febrile neutropenia: outline of management.

PubMed

Oberoi, Sapna; Suthar, Renu; Bansal, Deepak; Marwaha, R K

2013-02-01

Febrile neutropenia is a common emergency encountered in children receiving chemotherapy for a malignancy. Left untreated, it can lead to serious morbidity and mortality. Febrile neutropenia is suspected in any patient on chemotherapy who presents with fever. Prompt evaluation and management by the primary contact pediatrician is essential for a successful outcome. A detailed history and physical examination is warranted to identify source of infection, although two thirds of them may not have localizing symptoms or signs. Risk stratification is valuable in categorizing the severity and guiding therapy. Initial stabilization, prompt initiation of appropriate antibiotics and adequate supportive care are the cornerstone of treatment. Knowledge of the locally prevailing bacteriological profile and antimicrobial susceptibility data is crucial for each hospital/unit to frame and periodically modify guidelines for the choice of antimicrobials. Delay in initiating antimicrobials significantly worsens the outcome. Education of the family as well as the members of the treating unit is important in this regard. Pro-active steps must be taken to reduce incidence of hospital acquired sepsis. Diagnosis and management in relevance to the emergency room is reviewed and institutional practice is shared.

Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.

PubMed

Schubert, Julian; Siekierska, Aleksandra; Langlois, Mélanie; May, Patrick; Huneau, Clément; Becker, Felicitas; Muhle, Hiltrud; Suls, Arvid; Lemke, Johannes R; de Kovel, Carolien G F; Thiele, Holger; Konrad, Kathryn; Kawalia, Amit; Toliat, Mohammad R; Sander, Thomas; Rüschendorf, Franz; Caliebe, Almuth; Nagel, Inga; Kohl, Bernard; Kecskés, Angela; Jacmin, Maxime; Hardies, Katia; Weckhuysen, Sarah; Riesch, Erik; Dorn, Thomas; Brilstra, Eva H; Baulac, Stephanie; Møller, Rikke S; Hjalgrim, Helle; Koeleman, Bobby P C; Jurkat-Rott, Karin; Lehman-Horn, Frank; Roach, Jared C; Glusman, Gustavo; Hood, Leroy; Galas, David J; Martin, Benoit; de Witte, Peter A M; Biskup, Saskia; De Jonghe, Peter; Helbig, Ingo; Balling, Rudi; Nürnberg, Peter; Crawford, Alexander D; Esguerra, Camila V; Weber, Yvonne G; Lerche, Holger

2014-12-01

Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.

2016 Update of the Italian Pediatric Society Guidelines for Management of Fever in Children.

PubMed

Chiappini, Elena; Venturini, Elisabetta; Remaschi, Giulia; Principi, Nicola; Longhi, Riccardo; Tovo, Pier-Angelo; Becherucci, Paolo; Bonsignori, Francesca; Esposito, Susanna; Festini, Filippo; Galli, Luisa; Lucchesi, Bice; Mugelli, Alessandro; Marseglia, Gian Luigi; de Martino, Maurizio

2017-01-01

To review new scientific evidence to update the Italian guidelines for managing fever in children as drafted by the panel of the Italian Pediatric Society. Relevant publications in English and Italian were identified through search of MEDLINE and the Cochrane Database of Systematic Reviews from May 2012 to November 2015. Previous recommendations are substantially reaffirmed. Antipyretics should be administered with the purpose to control the child's discomfort. Antipyretics should be administered orally; rectal administration is discouraged except in the setting of vomiting. Combined use of paracetamol and ibuprofen is discouraged, considering risk and benefit. Antipyretics are not recommended preemptively to reduce the incidence of fever and local reactions in children undergoing vaccination, or in attempt to prevent febrile convulsions in children. Ibuprofen and paracetamol are not contraindicated in children who are febrile with asthma, with the exception of known cases of paracetamol- or nonsteroidal anti-inflammatory drug-induced asthma. Recent medical literature leads to reaffirmation of previous recommendations for use of antipyretics in children who are febrile. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence of PCR detectable malaria infection among febrile patients with a negative Plasmodium falciparum specific rapid diagnostic test in Zanzibar.

PubMed

Baltzell, Kimberly A; Shakely, Deler; Hsiang, Michelle; Kemere, Jordan; Ali, Abdullah Suleiman; Björkman, Anders; Mårtensson, Andreas; Omar, Rahila; Elfving, Kristina; Msellem, Mwinyi; Aydin-Schmidt, Berit; Rosenthal, Philip J; Greenhouse, Bryan

2013-02-01

We screened for malaria in 594 blood samples from febrile patients who tested negative by a Plasmodium falciparum-specific histidine-rich protein-2-based rapid diagnostic test at 12 health facilities in Zanzibar districts North A and Micheweni, from May to August 2010. Screening was with microscopy, polymerase chain reaction (PCR) targeting the cytochrome b gene (cytbPCR) of the four major human malaria species, and quantitative PCR (qPCR). The prevalence of cytbPCR-detectable malaria infection was 2% (12 of 594), including 8 P. falciparum, 3 Plasmodium malariae, and 1 Plasmodium vivax infections. Microscopy identified 4 of 8 P. falciparum infections. Parasite density as estimated by microscopy or qPCR was > 4,000 parasites/μL in 5 of 8 cytbPCR-detectable P. falciparum infections. The infections that were missed by the rapid diagnostic test represent a particular challenge in malaria elimination settings and highlight the need for more sensitive point-of-care diagnostic tools to improve case detection of all human malaria species in febrile patients.

Molecular Evidence of Malaria and Zoonotic Diseases Among Rapid Diagnostic Test-Negative Febrile Patients in Low-Transmission Season, Mali.

PubMed

Touré, Mahamoudou; Petersen, Pelle T; Bathily, Sidy N'd; Sanogo, Daouda; Wang, Christian W; Schiøler, Karin L; Konradsen, Flemming; Doumbia, Seydou; Alifrangis, Michael

2017-02-08

From November to December 2012 in Sélingué-Mali, blood samples from 88 febrile patients who tested negative by malaria Paracheck ® rapid diagnostic tests (RDTs) were used to assess the presence of sub-RDT Plasmodium falciparum as well as Borrelia , Coxiella burnetii , and Babesia applying molecular tools. Plasmodium sp. was present among 57 (60.2%) of the 88 malaria RDT-negative patients, whereas the prevalence of Borrelia , C. burnetii , and Babesia were 3.4% ( N = 3), 1.1% ( N = 1), and 0.0%, respectively. The additional diagnostic use of polymerase chain reaction (PCR) identified a high proportion of Plasmodium sp.-positive samples and although this may be a concern for malaria control, the respective PCR-identified malaria infections were less likely responsible for the observed fevers given the low parasite density. Also, the low infection levels of Borrelia and C. burnetii and lack of Babesia among the febrile patients call for further studies to assess the causes of fever among malaria RDT-negative patients in Sélingué. © The American Society of Tropical Medicine and Hygiene.

[Pathophysiology and diagnosis of cancer patients with febrile neutropenia].

PubMed

Saito, Takeshi; Aiba, Keisuke

2013-06-01

Exogenous pyrogens induce several cytokines which activate immune responses, and produce fever. In Japan, febrile neutropenia is defined as having an axillary temperature of>37. 5°C, and neutropenia showing an absolute neutrophil count (ANC)of<500 cells/mL or an ANC that is expected to reduce to<500 cells/mL during the next 48 hours. Signs and symptoms of inflammation are often attenuated or absent in neutropenic patients. Therefore, careful physical examination is required to detect subtle symptoms and signs of infection. As an initial assessment, laboratory tests should include the following: a ) complete blood cell count with differential leukocyte count and platelet count, b ) measurement of serum levels of creatinine, electrolytes, and hepatic transaminase enzymes, c ) serologic assay for fungal infection, and d ) at least 2 sets of blood cultures. Radiographical approaches are also important for detecting the focus of infection. Proper risk classification should be performed using the Multinational Association for Supportive Care in Cancer(MASCC)scoring system to distinguish high-risk and low-risk patients with febrile neutropenia.

Challenges of Establishing the Correct Diagnosis of Outbreaks of Acute Febrile Illnesses in Africa: The Case of a Likely Brucella Outbreak among Nomadic Pastoralists, Northeast Kenya, March–July 2005

PubMed Central

Ari, Mary D.; Guracha, Argata; Fadeel, Moustafa Abdel; Njuguna, Charles; Njenga, M. Kariuki; Kalani, Rosalia; Abdi, Hassan; Warfu, Osman; Omballa, Victor; Tetteh, Christopher; Breiman, Robert F.; Pimentel, Guillermo; Feikin, Daniel R.

2011-01-01

An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed. PMID:22049048

The seven sins in academic behavior in the natural sciences.

PubMed

van Gunsteren, Wilfred F

2013-01-02

"Seven deadly sins" in modern academic research and publishing can be condensed into a list ranging from poorly described experimental or computational setups to falsification of data. This Essay describes these sins and their ramifications, and serves as a code of best practice for researchers in their quest for scientific truth. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differintegration: The One Branch of Calculus

ERIC Educational Resources Information Center

Berry, Andrew J.

2007-01-01

How might one define a functional operator D[superscript I]f(x), say for f(x) = 1 + x[superscript 2] + sin x, such that D[superscript +1](1 + x[superscript 2] + sin x) = 2x + cos x and D[superscript -1](1 + x[superscript 2] + sin x) = x + x[superscript 3]/3 - cos x? Our task in this article is to describe such an operator using a single formula…

The human dark side: evolutionary psychology and original sin.

PubMed

Lee, Joseph; Theol, M

2014-04-01

Human nature has a dark side, something important to religions. Evolutionary psychology has been used to illuminate the human shadow side, although as a discipline it has attracted criticism. This article seeks to examine the evolutionary psychology's understanding of human nature and to propose an unexpected dialog with an enduring account of human evil known as original sin. Two cases are briefly considered: murder and rape. To further the exchange, numerous theoretical and methodological criticisms and replies of evolutionary psychology are explored jointly with original sin. Evolutionary psychology can partner with original sin since they share some theoretical likenesses and together they offer insights into the nature of what it means to be human.

Optimal Guidance Trajectories for a Nanosat Docking with a Non Cooperative Resident Space Object

DTIC Science & Technology

2014-03-07

12 − 3 sin 2 rref sin 2(kt)/2− (1 + cos 2iref)/8] + fx ÿ = −2(nc)ẋ− 3n2J2(R2e/2rref) sin2 iref sin(2kt) + fy z̈ = −(3c2 − 2)n2z + fz (24) where fx ...dynamics assumes three normalized controls: u = [ fx fxmax fy fymax fz fzmax ] (26) For simplicity, it is assumed that fimax = 1m/s2 for i = x, y, z...American Institute of Aeronautics and Astro - nautics, 2010. [7] G. Boyarko, O. Yakimenko, and M. Romano, Optimal rendezvous trajectories of a controlled

Louse-borne relapsing fever in Finland in two asylum seekers from Somalia.

PubMed

Hytönen, Jukka; Khawaja, Tamim; Grönroos, Juha O; Jalava, Anna; Meri, Seppo; Oksi, Jarmo

2017-01-01

We report two cases of louse-borne relapsing fever (LBRF) in young Somali asylum seekers having recently arrived to Finland. They had sought medical attention for a febrile illness. Blood smears were examined for suspected malaria, but instead, spirochete shaped bacteria were observed. The bacteria were confirmed as Borrelia recurrentis by PCR and sequencing. The patients survived, but their treatment was complicated by Jarisch-Herxheimer reaction. We conclude that LBRF must be considered as a diagnostic option in febrile refugees also in the northernmost parts of Europe. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Use of computed tomography abdomen and pelvis for investigation of febrile neutropenia in adult haematology patients.

PubMed

Lim, H Y; Ashby, M; Williams, B; Grigg, A

2016-11-01

We retrospectively evaluated the use of computed tomography abdomen and pelvis (CTAP) in febrile neutropenic autologous stem cell transplant (ASCT) and acute myeloid leukaemia (AML) patients. CTAP was more common in ASCT patients (59%) compared with AML (31%; P  < 0.001). Although abnormal findings were reported in 51%, only 10% resulted in therapy change (addition of anaerobic antibiotic/bowel rest), which would have otherwise been instituted based on clinical grounds. CTAP in these patients rarely provide useful information unsuspected clinically. © 2016 Royal Australasian College of Physicians.

Performance analysis of device-level SINS/ACFSS deeply integrated navigation method

NASA Astrophysics Data System (ADS)

Zhang, Hao; Qin, Shiqiao; Wang, Xingshu; Jiang, Guangwen; Tan, Wenfeng

2016-10-01

The Strap-Down Inertial Navigation System (SINS) is a widely used navigation system. The combination of SINS and the Celestial Navigation System (CNS) is one of the popular measures to constitute the integrated navigation system. A Star Sensor (SS) is used as a precise attitude determination device in CNS. To solve the problem that the star image obtained by SS under dynamic conditions is motion-blurred, the Attitude Correlated Frames (ACF) is presented and the star sensor which works based on ACF approach is named ACFSS. Depending on the ACF approach, a novel device-level SINS/ACFSS deeply integrated navigation method is proposed in this paper. Feedback to the ACF process from the error of the gyro is one of the typical characters of the SINS/CNS deeply integrated navigation method. Herein, simulation results have verified its validity and efficiency in improving the accuracy of gyro and it can be proved that this method is feasible in theory.

Resisting the therapeutic reduction: on the significance of sin.

PubMed

Delkeskamp-Hayes, Corinna

2007-01-01

Sin-talk, though politically incorrect, is indispensable. Placing human life under the "hermeneutic of sin" means acknowledging that one ought to aim flawlessly at God, and that one can fail in this endeavor. None of this can be appreciated within the contemporary post-Christian, mindset, which has attempted to reduce religion to morality and culture. In such a secular context, the guilt-feelings connected with the recognition of sin are considered to be harmful; the eternal benefit of a repentance is disregarded. Nevertheless, spirituality appears to have therapeutic benefits. Therefore attempts are made to re-locate within healthcare a religion shorn of its transcendent claims, so as then to harvest the benefits of a spirituality "saved from sin". This reduction of religiosity to its therapeutic function is nourished by a post-modern constructivist construal of religion. This article critically examines the dis-ingenuity marring such recasting, as well as the incoherence of related attempts to reduce transcendence to solidarity, and to re-shape the significance of religious rituals.

People Who Have Committed a Certain Sin Ought to Be Dead

ERIC Educational Resources Information Center

Leenaars, Antoon A.

2006-01-01

People who have committed a certain sin ought to be dead; I am a person who has committed that sin; therefore, I ought to be dead. Thus is the logic of a suicidal mind. Lester, Szaz, and others argue the "sinner" should always be allowed to kill him/herself. Shneidman, Leenaars and others do not agree. Once one knows the suicidal mind, it is easy…

S-Adenosyl-Homocysteine Is a Weakly Bound Inhibitor for a Flaviviral Methyltransferase

PubMed Central

Chen, Hui; Zhou, Bing; Brecher, Matthew; Banavali, Nilesh; Jones, Susan A.; Li, Zhong; Zhang, Jing; Nag, Dilip; Kramer, Laura D.; Ghosh, Arun K.; Li, Hongmin

2013-01-01

The methyltransferase enzyme (MTase), which catalyzes the transfer of a methyl group from S-adenosyl-methionine (AdoMet) to viral RNA, and generates S-adenosyl-homocysteine (AdoHcy) as a by-product, is essential for the life cycle of many significant human pathogen flaviviruses. Here we investigated inhibition of the flavivirus MTase by several AdoHcy-derivatives. Unexpectedly we found that AdoHcy itself barely inhibits the flavivirus MTase activities, even at high concentrations. AdoHcy was also shown to not inhibit virus growth in cell-culture. Binding studies confirmed that AdoHcy has a much lower binding affinity for the MTase than either the AdoMet co-factor, or the natural AdoMet analog inhibitor sinefungin (SIN). While AdoMet is a positively charged molecule, SIN is similar to AdoHcy in being uncharged, and only has an additional amine group that can make extra electrostatic contacts with the MTase. Molecular Mechanics Poisson-Boltzmann Sovation Area analysis on AdoHcy and SIN binding to the MTase suggests that the stronger binding of SIN may not be directly due to interactions of this amine group, but due to distributed differences in SIN binding resulting from its presence. The results suggest that better MTase inhibitors could be designed by using SIN as a scaffold rather than AdoHcy. PMID:24130807

S-adenosyl-homocysteine is a weakly bound inhibitor for a flaviviral methyltransferase.

PubMed

Chen, Hui; Zhou, Bing; Brecher, Matthew; Banavali, Nilesh; Jones, Susan A; Li, Zhong; Zhang, Jing; Nag, Dilip; Kramer, Laura D; Ghosh, Arun K; Li, Hongmin

2013-01-01

The methyltransferase enzyme (MTase), which catalyzes the transfer of a methyl group from S-adenosyl-methionine (AdoMet) to viral RNA, and generates S-adenosyl-homocysteine (AdoHcy) as a by-product, is essential for the life cycle of many significant human pathogen flaviviruses. Here we investigated inhibition of the flavivirus MTase by several AdoHcy-derivatives. Unexpectedly we found that AdoHcy itself barely inhibits the flavivirus MTase activities, even at high concentrations. AdoHcy was also shown to not inhibit virus growth in cell-culture. Binding studies confirmed that AdoHcy has a much lower binding affinity for the MTase than either the AdoMet co-factor, or the natural AdoMet analog inhibitor sinefungin (SIN). While AdoMet is a positively charged molecule, SIN is similar to AdoHcy in being uncharged, and only has an additional amine group that can make extra electrostatic contacts with the MTase. Molecular Mechanics Poisson-Boltzmann Sovation Area analysis on AdoHcy and SIN binding to the MTase suggests that the stronger binding of SIN may not be directly due to interactions of this amine group, but due to distributed differences in SIN binding resulting from its presence. The results suggest that better MTase inhibitors could be designed by using SIN as a scaffold rather than AdoHcy.

Understanding original antigenic sin in influenza with a dynamical system.

PubMed

Pan, Keyao

2011-01-01

Original antigenic sin is the phenomenon in which prior exposure to an antigen leads to a subsequent suboptimal immune response to a related antigen. Immune memory normally allows for an improved and rapid response to antigens previously seen and is the mechanism by which vaccination works. I here develop a dynamical system model of the mechanism of original antigenic sin in influenza, clarifying and explaining the detailed spin-glass treatment of original antigenic sin. The dynamical system describes the viral load, the quantities of healthy and infected epithelial cells, the concentrations of naïve and memory antibodies, and the affinities of naïve and memory antibodies. I give explicit correspondences between the microscopic variables of the spin-glass model and those of the present dynamical system model. The dynamical system model reproduces the phenomenon of original antigenic sin and describes how a competition between different types of B cells compromises the overall effect of immune response. I illustrate the competition between the naïve and the memory antibodies as a function of the antigenic distance between the initial and subsequent antigens. The suboptimal immune response caused by original antigenic sin is observed when the host is exposed to an antigen which has intermediate antigenic distance to a second antigen previously recognized by the host's immune system.

A Feasibility Analysis of Land-Based SINS/GNSS Gravimetry for Groundwater Resource Detection in Taiwan

PubMed Central

Chiang, Kai-Wei; Lin, Cheng-An; Kuo, Chung-Yen

2015-01-01

The integration of the Strapdown Inertial Navigation System and Global Navigation Satellite System (SINS/GNSS) has been implemented for land-based gravimetry and has been proven to perform well in estimating gravity. Based on the mGal-level gravimetry results, this research aims to construct and develop a land-based SINS/GNSS gravimetry device containing a navigation-grade Inertial Measurement Unit. This research also presents a feasibility analysis for groundwater resource detection. A preliminary comparison of the kinematic velocities and accelerations using multi-combination of GNSS data including Global Positioning System, Global Navigation Satellite System, and BeiDou Navigation Satellite System, indicates that three-system observations performed better than two-system data in the computation. A comparison of gravity derived from SINS/GNSS and measured using a relative gravimeter also shows that both agree reasonably well with a mean difference of 2.30 mGal. The mean difference between repeat measurements of gravity disturbance using SINS/GNSS is 2.46 mGal with a standard deviation of 1.32 mGal. The gravity variation because of the groundwater at Pingtung Plain, Taiwan could reach 2.72 mGal. Hence, the developed land-based SINS/GNSS gravimetry can sufficiently and effectively detect groundwater resources. PMID:26426019

A Feasibility Analysis of Land-Based SINS/GNSS Gravimetry for Groundwater Resource Detection in Taiwan.

PubMed

Chiang, Kai-Wei; Lin, Cheng-An; Kuo, Chung-Yen

2015-09-29

The integration of the Strapdown Inertial Navigation System and Global Navigation Satellite System (SINS/GNSS) has been implemented for land-based gravimetry and has been proven to perform well in estimating gravity. Based on the mGal-level gravimetry results, this research aims to construct and develop a land-based SINS/GNSS gravimetry device containing a navigation-grade Inertial Measurement Unit. This research also presents a feasibility analysis for groundwater resource detection. A preliminary comparison of the kinematic velocities and accelerations using multi-combination of GNSS data including Global Positioning System, Global Navigation Satellite System, and BeiDou Navigation Satellite System, indicates that three-system observations performed better than two-system data in the computation. A comparison of gravity derived from SINS/GNSS and measured using a relative gravimeter also shows that both agree reasonably well with a mean difference of 2.30 mGal. The mean difference between repeat measurements of gravity disturbance using SINS/GNSS is 2.46 mGal with a standard deviation of 1.32 mGal. The gravity variation because of the groundwater at Pingtung Plain, Taiwan could reach 2.72 mGal. Hence, the developed land-based SINS/GNSS gravimetry can sufficiently and effectively detect groundwater resources.

Salpingitis Isthmica Nodosa: Technical Success and Outcome of Fluoroscopic Transcervical Fallopian Tube Recanalization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houston, J. Graeme; Machan, Lindsay S.

1998-01-15

Purpose: To evaluate the technical success and outcome of fallopian tube recanalization (FTR) in salpingitis isthmica nodosa (SIN). Methods: SIN is a well-recognized pathological condition affecting the proximal fallopian tube and is associated with infertility and ectopic pregnancy. We reviewed the presentations, films, and case records of all patients attending for FTR for infertility from 1990 to 1994. Technical success and total, intrauterine, and ectopic pregnancy rates at follow-up were determined. Results: SIN was observed in 22 of 349 (6%) patients. FTR was attempted in 34 tubes in these 22 patients. Technical success was achieved in 23 of 34 (68%)more » tubes affected by SIN. In 5 of the 11 failed recanalizations, failure was due to distal obstruction. At least one tube was patent on selective postprocedural salpingography in 17 of 22 (77%) patients. There were no recorded perforations or complications. At follow-up (mean 14 months), total, intrauterine, and ectopic pregnancy rates were 23%, 18%, and 4.5%, respectively. Conclusion: FTR in SIN is technically successful and, compared with previously reported results in unselected infertility patients, is associated with only a slightly less favorable intrauterine pregnancy rate and a comparable ectopic pregnancy rate. The findings of SIN at FTR should not discourage attempted fluoroscopic transcervical recanalization.« less

Optimization and evaluation of pluronic lecithin organogels as a transdermal delivery vehicle for sinomenine.

PubMed

Ba, Wenqiang; Li, Zhou; Wang, Lisheng; Wang, Ding; Liao, Weiguo; Fan, Wentao; Wu, Yinai; Liao, Fengyun; Yu, Jianye

2016-08-01

The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box-Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (Jss) of SIN from PLO was 146.55 ± 2.93 μg/cm(2)/h, significantly higher than that of gel (120.39 μg/cm(2)/h) and the amount of SIN deposited in skin from the PLO was 10.08 ± 0.86 μg/cm(2), significantly larger than that from gel (6.01 ± 0.04 μg/cm(2)). In vivo skin microdialysis studies showed that the maximum concentration (Cmax) of SIN from PLO in "permeation study" and "drug-deposition study" were 150.27 ± 20.85 μg/ml and 67.95 μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73 μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.

Measurement of sin 2 θ eff lept using e + e - pairs from γ * / Z bosons produced in p p ¯ collisions at a center-of-momentum energy of 1.96 TeV

DOE PAGES

Aaltonen, T.; Amerio, S.; Amidei, D.; ...

2016-06-28

Here, at the Fermilab Tevatron proton-antiproton (pmore » $$\\bar{p}$$) collider, Drell-Yan lepton pairs are produced in the process p$$\\bar{p}$$→e +e -+X through an intermediate γ*/Z boson. The forward-backward asymmetry in the polar-angle distribution of the e - as a function of the e +e --pair mass is used to obtain sin 2θ$$lept\\atop{eff}$$, the effective leptonic determination of the electroweak-mixing parameter sin2θW. The measurement sample, recorded by the Collider Detector at Fermilab (CDF), corresponds to 9.4 fb -1 of integrated luminosity from p$$\\bar{p}$$ collisions at a center-of-momentum energy of 1.96 TeV, and is the full CDF Run II data set. The value of sin 2θ$$lept\\atop{eff}$$ is found to be 0.23248±0.00053. The combination with the previous CDF measurement based on μ +μ - pairs yields sin 2θ$$lept\\atop{eff}$$=0.23221±0.00046. This result, when interpreted within the specified context of the standard model assuming sin 2θW=1-M$$2\\atop{W}$$/M$$2\\atop{Z}$$ and that the W- and Z-boson masses are on-shell, yields sin 2θW=0.22400±0.00045, or equivalently a W-boson mass of 80.328±0.024 GeV/c 2.« less

Study on UKF based federal integrated navigation for high dynamic aviation

NASA Astrophysics Data System (ADS)

Zhao, Gang; Shao, Wei; Chen, Kai; Yan, Jie

2011-08-01

High dynamic aircraft is a very attractive new generation vehicles, in which provides near space aviation with large flight envelope both speed and altitude, for example the hypersonic vehicles. The complex flight environments for high dynamic vehicles require high accuracy and stability navigation scheme. Since the conventional Strapdown Inertial Navigation System (SINS) and Global Position System (GPS) federal integrated scheme based on EKF (Extended Kalman Filter) is invalidation in GPS single blackout situation because of high speed flight, a new high precision and stability integrated navigation approach is presented in this paper, in which the SINS, GPS and Celestial Navigation System (CNS) is combined as a federal information fusion configuration based on nonlinear Unscented Kalman Filter (UKF) algorithm. Firstly, the new integrated system state error is modeled. According to this error model, the SINS system is used as the navigation solution mathematic platform. The SINS combine with GPS constitute one error estimation filter subsystem based on UKF to obtain local optimal estimation, and the SINS combine with CNS constitute another error estimation subsystem. A non-reset federated configuration filter based on partial information is proposed to fuse two local optimal estimations to get global optimal error estimation, and the global optimal estimation is used to correct the SINS navigation solution. The χ 2 fault detection method is used to detect the subsystem fault, and the fault subsystem is isolation through fault interval to protect system away from the divergence. The integrated system takes advantages of SINS, GPS and CNS to an immense improvement for high accuracy and reliably high dynamic navigation application. Simulation result shows that federated fusion of using GPS and CNS to revise SINS solution is reasonable and availably with good estimation performance, which are satisfied with the demands of high dynamic flight navigation. The UKF is superior than EKF based integrated scheme, in which has smaller estimation error and quickly convergence rate.

Design and Phenomenology of the FEBSTAT Study

PubMed Central

Hesdorffer, Dale C; Shinnar, Shlomo; Lewis, Darrell V; Moshé, Solomon L; Nordli, Douglas R; Pellock, John M; MacFall, James; Shinnar, Ruth C; Masur, David; Frank, L Matthew; Epstein, Leon G; Litherland, Claire; Seinfeld, Syndi; Bello, Jacqueline A; Chan, Stephen; Bagiella, Emilia; Sun, Shumei

2012-01-01

Purpose Febrile status epilepticus (FSE) has been associated with hippocampal injury and subsequent hipppocampal sclerosis (HS) and temporal lobe epilepsy. The FEBSTAT study was designed to prospectively examine the association between prolonged febrile seizures and development of HS and associated temporal lobe epilepsy, one of the most controversial issues in epilepsy. We report on the baseline phenomenology of the final cohorts as well as detailed aims and methodology. Methods The “Consequences of Prolonged Febrile Seizures in Childhood” (FEBSTAT) study is a prospective, multicenter study. Enrolled are children, aged 1 month to 6 years, presenting with a febrile seizure lasting 30 minutes or more based upon ambulance, emergency department, and hospital records, and parental interview. At baseline, procedures included an MRI and EEG done within 72 hours of FSE, and a detailed history and neurological examination. Baseline development and behavior are assessed at one month. The baseline assessment is repeated, with age- appropriate developmental testing at one and five years after enrollment as well as at the development of epilepsy and one year after that. Telephone calls every three months document further seizures. Two other groups of children are included: a ‘control’ group consisting of children with a first febrile seizure ascertained at Columbia University and with almost identical baseline and one year follow-up examinations and a pilot cohort of FSE from Duke University. Key findings The FEBSTAT cohort consists of 199 children with a median age at baseline of 16.0 months (Interquartile range (IQR)=12.0–24.0) and a median duration of FSE of 70.0 minutes (IQR=47.0–110.0). Seizures were continuous in 57.3% and behaviorally intermittent (without recovery in between) in 31.2%; most were partial (4;2.0%) or secondary generalized (65.8%), and almost all (98.0%) culminated in a generalized tonic clonic seizure. Of the 199 children, 86.4% had normal development and 20% had prior febrile seizures. In one third of cases, FSE was unrecognized in the emergency department. The Duke existing cohort consists of 23 children with a median age of FSE onset of 18.0 months (IQR 14.0–28.0) and median duration of FSE of 90.0 minutes (IQR 50.0–170.0). The Columbia control cohort consists of 159 children with a first febrile seizure who received almost the same work-up as the FEBSTAT cohort at baseline and at one-year. They were followed by telephone every 4 months for a median of 42 months. Among the control cohort, 64.2% had a first simple FS, 26.4% had a first complex FS that was not FSE, and 9.4% had FSE. Among the 15 with FSE, the median age at onset was 14.0 months (IQR 12.0–20.0) and the median duration of FSE was 43.0 minutes (IQR 35.0–75.0). Significance The FEBSTAT study presents an opportunity to prospectively study the relationship between FSE and acute hippocampal damage, the development of MTS, epilepsy (particularly TLE), and impaired hippocampal function in a large cohort. It is hoped that this study may illuminate a major mystery in clinical epilepsy today, and permit the development of interventions designed to prevent the sequelae of FSE. PMID:22742587

[The use of teicoplanin in neutropenic patients: values and limits].

PubMed

Espinouse, D; Chomarat, M

1990-06-01

The efficacy and the safety of teicoplanin were evaluated for the treatment of febrile episodes in neutropenic patients. A total of 18 patients received teicoplanin once daily as an intravenous injection of 200 mg in 6 patients (after a loading dose of 400 mg) or 400 mg in 12 patients (loading dose: 800 mg). The mean duration of therapy was 15.9 days (range 9 to 39 days). In all patients teicoplanin was combined with another antibiotic usually a beta-lactam. Thirteen of 18 patients were successfully treated. Three febrile episodes proved to be microbiologically documented infections and were cured by teicoplanin: one Streptococcus mitis and two methicillin-resistant (methi-R) Staphylococcus epidermidis bacteremias. Neither toxicity nor side effects were observed in the reported group. Six patients experiencing reactions to vancomycin (2 cases of cutaneous allergy) or to vancomycin and amphotericin B combination (4 cases of nephrotoxicity) were subsequently treated with teicoplanin without any evidence of cross-sensitivity. We observed emergence of teicoplanin-resistant coagulase-negative Staphylococcus in 3 patients receiving teicoplanin: 20, 18 and 8 days after a first febrile episode cured by teicoplanin and a beta-lactam, they developed fever while receiving the same antibiotic regimen. Methi-R Staphylococcus epidermidis was isolated from blood cultures in the first patient and methi-R Staphylococcus haemolyticus in the two other patients. In one patient, successfully treated by teicoplanin for a first febrile episode related to a methi-R Staphylococcus epidermidis, emergence of Staphylococcus haemolyticus occurred 8 days later while the patient was on teicoplanin therapy (6 mg/kg). MICs of teicoplanin were 16 mg/l for the two Staphylococcus strains isolated in this patient.(ABSTRACT TRUNCATED AT 250 WORDS)

New prediction model for diagnosis of bacterial infection in febrile infants younger than 90 days.

PubMed

Vujevic, Matea; Benzon, Benjamin; Markic, Josko

2017-01-01

Vujevic M, Benzon B, Markic J. New prediction model for diagnosis of bacterial infection in febrile infants younger than 90 days. Turk J Pediatr 2017; 59: 261-268. Due to non-specific clinical presentation in febrile infants, extensive laboratory testing is often carried out to distinguish simple viral disease from serious bacterial infection (SBI). Objective of this study was to compare efficacy of different biomarkers in early diagnosis of SBI in infants < 90 days old. Also, we developed prediction models with whom it will be possible to diagnose SBI with more accuracy than with any biomarkers independently. Febrile < 90-day-old infants hospitalized in 2-year-period at Department of Pediatrics, University Hospital Centre Split with suspicion of having SBI were included in this study. Retrospective cohort analysis of data acquired from medical records was performed. Out of 181 enrolled patients, SBI was confirmed in 70. Most common diagnosis was urinary tract infection (68.6%), followed by pneumonia (12.9%), sepsis (11.4%), gastroenterocolitis (5.7%) and meningitis (1.4%). Male gender was shown to be a risk factor for SBI in this population (p=0.008). White blood cell count (WBC), absolute neutrophil count (ANC) and C-reactive protein (CRP) were confirmed as the independent predictors of SBI, with CRP as the best one. Two prediction models built by combining biomarkers and clinical variables were selected as optimal with sensitivities of 74.3% and 75.7%, and specificities of 88.3% and 86%. Evidently, CRP is a more superior biomarker in diagnostics of SBI comparing to WBC and ANC. Prediction models were shown to be better in predicting SBI than independent biomarkers. Although both showed high sensitivity and specificity, their true strength should be determined using validation cohort.

Role of procalcitonin in predicting dilating vesicoureteral reflux in young children hospitalized with a first febrile urinary tract infection.

PubMed

Sun, Hai-Lun; Wu, Kang-Hsi; Chen, Shan-Ming; Chao, Yu-Hua; Ku, Min-Sho; Hung, Tong-Wei; Liao, Pen-Fen; Lue, Ko-Huang; Sheu, Ji-Nan

2013-09-01

The aim of this article was to assess the usefulness of procalcitonin (PCT) as a marker for predicting dilating (grades III-V) vesicoureteral reflux (VUR) in young children with a first febrile urinary tract infection. Children ≤2 years of age with a first febrile urinary tract infection were prospectively evaluated. Serum samples were tested for PCT at the time of admission to a tertiary hospital. All children underwent renal ultrasonography (US), Tc-dimercaptosuccinic acid renal scan, and voiding cystourethrography. The diagnostic characteristics of PCT test for acute pyelonephritis and dilating VUR were calculated. Of 272 children analyzed (168 boys and 104 girls; median age, 5 months), 169 (62.1%) had acute pyelonephritis. There was VUR demonstrated in 97 (35.7%), including 70 (25.7%) with dilating VUR. The median PCT value was significantly higher in children with VUR than in those without (P < 0.001). Using a PCT cutoff value of ≥1.0 ng/mL, the sensitivity and negative predictive value for predicting dilating VUR were 94.3% and 95.4%, respectively, for PCT, and 97.1% and 97.8%, respectively, for the combined PCT and US studies, whereas the positive and negative likelihood ratios were 2.03 and 0.107, respectively, for PCT, and 1.72 and 0.067, respectively, for the combined studies. By multivariate analysis, high PCT values and abnormalities on US were independent predictors of dilating VUR. PCT is useful for diagnosing acute pyelonephritis and predicting dilating VUR in young children with a first febrile urinary tract infection. A voiding cystourethrography is indicated only in children with high PCT values (≥1.0 ng/mL) and/or abnormalities found on a US.

Comparison of procalcitonin and different guidelines for first febrile urinary tract infection in children by imaging.

PubMed

Liao, Pei-Fen; Ku, Min-Sho; Tsai, Jeng-Dau; Choa, Yu-Hua; Hung, Tung-Wei; Lue, Ko-Huang; Sheu, Ji-Nan

2014-09-01

We examined the ability of a procalcitonin (PCT) protocol to detect vesicoureteral reflux (VUR) and renal scarring (RS), evaluated procedural costs and radiation burden, and compared four representative guidelines for children with their first febrile urinary tract infection (UTI). Children aged ≤2 years with their first febrile UTI who underwent renal ultrasonography (US), acute and late technetium-99m ((99m)Tc)-dimercaptosuccinic acid scan, and voiding cystourethrography were prospectively studied. The representative guidelines applied in a retrospective simulation included the American Academy of Pediatrics (AAP), National Institute of Clinical Excellence, top-down approach (TDA), and Italian Society of Pediatric Nephrology (ISPN). These were compared in terms of ability to detect abnormalities, procedural costs and radiation. Of 278 children analyzed, 172 (61.9%) had acute pyelonephritis. There was VUR in 101 (36.3%) children, including 73 (26.3%) with grades III-V VUR. RS was identified in 75 (27.0%) children. To detect VUR, TDA and PCT had the highest sensitivity for grades I-V VUR (80.2%) and III-V VUR (94.5%), respectively, whereas AAP had the highest specificity for I-V VUR (77.4%) and III-V VUR (78.0%), respectively. TDA and PCT had the highest sensitivity (100%) for detecting RS. The highest cost and radiation dose was associated with TDA, whereas AAP had the least expenditure and radiation exposure. By multivariate analysis, PCT and VUR, especially grades III-V, were independent predictors of RS. There is no perfect guideline for first febrile UTI children. The PCT protocol has good ability for detecting high-grade VUR and RS. If based on available imaging modalities and reducing cost and radiation burden, clinical suggestions in the AAP guidelines represent a considerable protocol.

Probabilities of Dilating Vesicoureteral Reflux in Children with First Time Simple Febrile Urinary Tract Infection, and Normal Renal and Bladder Ultrasound.

PubMed

Rianthavorn, Pornpimol; Tangngamsakul, Onjira

2016-11-01

We evaluated risk factors and assessed predicted probabilities for grade III or higher vesicoureteral reflux (dilating reflux) in children with a first simple febrile urinary tract infection and normal renal and bladder ultrasound. Data for 167 children 2 to 72 months old with a first febrile urinary tract infection and normal ultrasound were compared between those who had dilating vesicoureteral reflux (12 patients, 7.2%) and those who did not. Exclusion criteria consisted of history of prenatal hydronephrosis or familial reflux and complicated urinary tract infection. The logistic regression model was used to identify independent variables associated with dilating reflux. Predicted probabilities for dilating reflux were assessed. Patient age and prevalence of nonEscherichia coli bacteria were greater in children who had dilating reflux compared to those who did not (p = 0.02 and p = 0.004, respectively). Gender distribution was similar between the 2 groups (p = 0.08). In multivariate analysis older age and nonE. coli bacteria independently predicted dilating reflux, with odds ratios of 1.04 (95% CI 1.01-1.07, p = 0.02) and 3.76 (95% CI 1.05-13.39, p = 0.04), respectively. The impact of nonE. coli bacteria on predicted probabilities of dilating reflux increased with patient age. We support the concept of selective voiding cystourethrogram in children with a first simple febrile urinary tract infection and normal ultrasound. Voiding cystourethrogram should be considered in children with late onset urinary tract infection due to nonE. coli bacteria since they are at risk for dilating reflux even if the ultrasound is normal. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The weakening effect of soluble epoxide hydrolase inhibitor AUDA on febrile response to lipopolysaccharide and turpentine in rat.

PubMed

Piotrowski, Jakub; Jędrzejewski, Tomasz; Pawlikowska, Małgorzata; Pacuła, Agata Joanna; Ścianowski, Jacek; Kozak, Wiesław

2017-11-01

A still growing body of evidence suggests the importance of epoxyeicosatrienoic acids (EETs) in the regulation of inflammatory response; therefore, drugs that stabilize their levels by targeting the soluble epoxide hydrolase (sEH), an enzyme responsible for their metabolism, are currently under investigation. The effect of sEH inhibitors on molecular components of fever mechanism, i.e., on synthesis of pro-inflammatory cytokines or prostaglandins, has been repeatedly proven; however, the hypothesis that sEH inhibitors affect febrile response has never been tested. The aim of this study was to examine if sEH inhibition affects core body temperature (Tb) as well as Tb changes during febrile response to infectious (lipopolysaccharide; LPS) or non-infectious (turpentine; TRP) stimuli. Male Wistar rats were implanted intra-abdominally with miniature biotelemeters to monitor Tb. A potent sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) was suspended in olive oil and administrated into animals in the intraperitoneal (i.p.) dose of 15 mg/kg, which, as we showed, has no significant influence on normal Tb. We have found that AUDA injected 3 h after LPS (50 μg/kg i.p.) significantly weakened febrile rise of Tb. Moreover, injection of sEH inhibitor 7 h after turpentine (administrated subcutaneously in a dose of 100 μL/rat) markedly reduced the peak period of aseptic fever. Obtained results provide first experimental evidence that sEH inhibitors possess anti-pyretic properties. Therefore, medicines targeting sEH enzymatic activity should be considered as a complement to the arsenal of topical medications used to treat fever especially in clinical situations when non-steroidal anti-inflammatory drugs are ineffective.

High-risk febrile neutropenia in Auckland 2003-2004: the influence of the microbiology laboratory on patient treatment and the use of pathogen-specific therapy.

PubMed

Ritchie, S; Palmer, S; Ellis-Pegler, R

2007-01-01

International guidelines recommend routine microbiological assessment of patients with febrile neutropenia, but do not recommend a change from broad-spectrum antibiotic therapy to pathogen-specific therapy when a clinically relevant organism has been isolated. The aim of the study was to determine the aetiology of febrile neutropenia in adult haematology patients at Auckland City Hospital, to document the changes in treatment made following isolation of a clinically relevant organism and to assess adverse outcomes in any patient who received pathogen-specific therapy after a positive culture result. The results of all microbiological tests together with antibiotic therapy were recorded from consecutive patients with fever and a neutrophil count <0.5 x 10(9)/L over 1 year beginning in May 2003. One thousand one hundred and ninety-six specimens were collected from 81 patients during 116 episodes of febrile neutropenia. A pathogen was isolated from blood cultures in 40 episodes: Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for 35%. Isolation of a pathogen from blood cultures resulted in a change of treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes, antibiotic therapy was optimized to a single pathogen-specific agent. No adverse events or subsequent changes in antibiotic therapy occurred in any of these 12 patients. Isolation of a pathogen from specimens other than blood seldom led to a change in therapy. Isolation of a pathogen from blood cultures often allows antibiotic therapy to be simplified to a pathogen-specific regimen. Further study of this approach is warranted.

Childhood febrile illness and the risk of myopia in UK Biobank participants.

PubMed

Guggenheim, J A; Williams, C

2016-04-01

Historical reports suggest febrile illness during childhood is a risk factor for myopia. The establishment of the UK Biobank provided a unique opportunity to investigate this relationship. We studied a sample of UK Biobank participants of White ethnicity aged 40-69 years old who underwent autorefraction (N=91 592) and were classified as myopic (≤-0.75 Dioptres (D)), highly myopic (≤-6.00 D), or non-myopic (>-0.75 D). Self-reported age at diagnosis of past medical conditions was ascertained during an interview with a nurse at a Biobank assessment centre. Logistic regression analysis was used to calculate the odds ratio (OR) for myopia or high myopia associated with a diagnosis before age 17 years of each of nine febrile illnesses, after adjusting for potential confounders (age, sex, highest educational qualification, and birth order). Rubella, mumps, and pertussis were associated with myopia: rubella, OR=1.38, 95% CI: 1.03-1.85, P=0.030; mumps, OR=1.32, 95% CI: 1.07-1.64, P=0.010; and pertussis, OR=1.39, 95% CI 1.03-1.87, P=0.029. Measles, rubella, and pertussis were associated with high myopia: measles, OR=1.48, 95% CI: 1.07-2.07, P=0.019; rubella, OR=1.94, 95% CI: 1.12-3.35, P=0.017; and pertussis, OR=2.15, 95% CI: 1.24-3.71, P=0.006. The evidence did not support an interaction between education and febrile illness in explaining the above risks. A history of childhood measles, rubella, or pertussis was associated with high myopia, whereas a history of childhood rubella, mumps, or pertussis was associated with any myopia. The reasons for these associations are unclear.

Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures.

PubMed

Klein, Nicola P; Fireman, Bruce; Yih, W Katherine; Lewis, Edwin; Kulldorff, Martin; Ray, Paula; Baxter, Roger; Hambidge, Simon; Nordin, James; Naleway, Allison; Belongia, Edward A; Lieu, Tracy; Baggs, James; Weintraub, Eric

2010-07-01

In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine. Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses. MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6). Among 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.

Positioning irrigation of contrast cystography for diagnosis of occult vesicoureteric reflux: association with technetium-99m dimercaptosuccinic acid scans.

PubMed

Berger, Christoph; Becker, Tanja; Koen, Mark; Zeino, Mazen; Fitz, Friedrich; Beheshti, Mohsen; Wolf-Kohlmeier, Iris; Haim, Silke; Riccabona, Marcus

2013-12-01

Positioning irrigation of contrast (PIC) cystography identifies occult or PIC vesicoureteral reflux (PIC-VUR) in children with recurrent febrile urinary tract infections (UTI) but no vesicoureteric reflux (VUR) on standard voiding cystourethrogram (VCUG). We sought to identify the relationship between PIC-VUR and renal scarring in technetium-99m dimercaptosuccinic acid (DMSA) scans. We retrospectively analysed PIC cystograms and DMSA scans for 154 kidneys in 81 children (65 girls; 16 boys; median age, 4.7 years; range, 0.9-15.2). Renal scarring was graded on a scale of 0-3. DMSA scans were pathologic in 66 patients (81%). Children had experienced mean 3.8 febrile UTI (range 1-25). Forty-seven (58%) children had a history of reflux, including 15 (19%) with previous anti-reflux operations. Indications for PIC cystography were recurrence of febrile UTI after either bilateral negative VCUG (66 children) or unilateral VUR (15 children) with contralateral/bilateral scarring or reflux that had changed sides in subsequent VCUGs. PIC-VUR was bilateral in 63, unilateral in 12, and absent in 6 children. Statistically significant associations between PIC-VUR grade and severity of renal scarring were identified in inter-individual (n = 77, p = 0.017) and intra-individual (refluxing vs. nonrefluxing kidney; n = 12, p = 0.008) analyses. After excluding patients with history of VUR, statistical significance was maintained in inter-individual analysis (n = 49; p = 0.018). The data suggest an association between PIC-VUR and severity of renal scarring, and legitimise the use of PIC cystography in children with renal scarring due to recurrent febrile UTI but negative findings on VCUG. Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

[Rash and fever illness caused by herpes simplex virus type 1 needs to be distinguished from hand, foot and mouth disease].

PubMed

Zhu, Shuang-Li; Liu, Jian-Feng; Sun, Qiang; Li, Jing; Li, Xiao-Lei; Zhang, Yong; Chen, Ying; Wen, Xiao-Yun; Yan, Dong-Mei; Huang, Guo-Hong; Zhang, Bao-Min; Zhang, Bo; An, Hong-Qiu; Li, Hui; Xu, Wen-Bo

2013-06-01

An epidemic of rash and fever illnesses suspected of hand, foot and mouth disease (HFMD) occurred in Gansu Province of China in 2008, laboratory tests were performed in order to identify the pathogen that caused this epidemic. Eight clinical specimens collected from the 4 patients (each patient has throat swab and herpes fluid specimens) with rash and febrile illness, were inoculated onto RD and HEp-2 cells for virus isolation, and the viral nucleic acid was then extracted with the positive virus isolates, the dual-channel real-time reverse transcript-polymerase chain reaction (RT-PCR) was performed to detect the nucleic acid of human enterovirus (HEV) in the viral isolates at the same time. For the viral isolates with the negative results of HEV, a sequence independent single primer amplification technique (SISPA) was used for "unknown pathogen" identification. Totally, 6 viral isolates were identified as herpes simplex virus type 1 (HSV-1). Comprehensive analyses results of the clinical manifestations of the patients, epidemiological findings and laboratory test indicated that this epidemic of rash and febrile illness was caused by HSV-1. The differences among the gG region of 6 HSV-1 isolates at nucleotide level and amino acid level were all small, and the identities were up to 98. 8% and 97.9%, respectively, showing that this outbreak was caused by only one viral transmission chain of HSV-1. HSV-1 and other viruses that cause rash and febrile illnesses need differential diagnosis with HFMD. The etiology of rash and febrile illness is sometimes difficult to distinguish from the clinical symptoms and epidemiological data, the laboratory diagnosis is therefore critical.

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PubMed

Elting, L S; Rubenstein, E B; Rolston, K; Cantor, S B; Martin, C G; Kurtin, D; Rodriguez, S; Lam, T; Kanesan, K; Bodey, G

2000-11-01

To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

A retrospective review of vital signs and clinical outcomes of febrile infants younger than 3 months old presenting to the emergency department.

PubMed

Chong, Shu-Ling; Ong, Gene Yong-Kwang; Chin, Wendy Yi Wen; Chua, John Mingzhou; Nair, Praseetha; Ong, Alicia Shu Zhen; Ng, Kee Chong; Maconochie, Ian

2018-01-01

Febrile infants younger than 3 months old present a diagnostic dilemma to the emergency physician. We aim to describe a large population of febrile infants less than 3 months old presenting to a pediatric emergency department (ED) and to assess the performance of current heart rate guidelines in the prediction of serious infections (SI). We performed a retrospective review of febrile infants younger than 3 months old, between March 2015 and Feb 2016, in a large tertiary pediatric ED. We documented the primary outcome of SI for each infant, as well as the clinical findings, vital signs, and Severity Index Score (SIS). We assessed the performance of the Paediatric Canadian Triage and Acuity Scale (PaedCTAS), Advanced Pediatric Life Support (APLS) guidelines and Fleming normal reference values, using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under receiver operating characteristics curve (AUC). 1057 infants were analyzed, with 326 (30.6%) infants diagnosed with SI. High temperature, tachycardia, and low SIS score were significantly associated with SI. Item analysis showed that the SIS performance was driven by the presence of mottling (p = 0.003) and high temperature (p<0.001). The APLS guideline had the highest sensitivity (66.0%, 95% CI 60.5-71.1%), NPV (73.3%, 95% CI 69.7-76.5%) and AUC (0.538), while the PaedCTAS (2 standard deviation from normal) had the highest specificity (98.5%, 95% CI 97.3-99.3%) and PPV (55.2%, 95% CI 32.7-71.0%). Current guidelines on infantile heart rates have a variable performance. In our study, the APLS heart rate guidelines performed with the highest sensitivity, but no individual guideline predicted for SIs satisfactorily.

Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study

PubMed Central

Lahat, Eli; Goldman, Michael; Barr, Joseph; Bistritzer, Tzvi; Berkovitch, Matithyahu

2000-01-01

Objective To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures. Design Prospective randomised study. Setting Paediatric emergency department in a general hospital. Subjects 47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period. Interventions Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg). Main outcome measures Time from arrival at hospital to starting treatment and cessation of seizures. Results Intranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7.9 to 8.3). No significant side effects were observed in either group. Conclusion Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home. PMID:10884257

Refining the Association of Fever with Functional Outcome in Aneurysmal Subarachnoid Hemorrhage.

PubMed

Kramer, Christopher L; Pegoli, Marianna; Mandrekar, Jay; Lanzino, Giuseppe; Rabinstein, Alejandro A

2017-02-01

We analyzed the impact of cause, severity, and duration of fever on functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Fever characteristics were analyzed in 584 consecutive patients with aSAH. Fever was defined as core body temperature ≥38.3 °C on ≥2 consecutive days. Subfebrile measurements were those between 37 and 38.2 °C. Febrile and subfebrile loads were the number of hours with fever or subfebrile measurements, respectively. Univariate and multivariate logistic regression models were developed to define predictors of outcome using various categorizations of fever cause, severity, and duration. Febrile measurements were observed in 281/584 (48.1 %) patients, recurring over a mean duration of 2.1 ± 3.0 days. Early fever within 24 and 72 h was encountered in 69 (11.9 %) and 110 (18.9 %) of patients, respectively. An infectious source was discovered in 126 (44.8 %) febrile patients. On univariate analysis, days of fever, febrile load, and fever onset within 24 and 72 h were associated with poor outcome (all p < 0.001); but subfebrile load was not (p = 0.56). On multivariate model constructed with all variables associated with outcome on univariate analyses, days of fever remained independently associated with poor outcome (OR 1.14 of poor outcome per day of fever, 95 % CI 1.06-1.22; p = 0.0006) displacing all other fever measures from the final model. Early onset of fever, number of hours with fever, and especially days of fever are associated with poor functional outcome. Conversely, subfebrile load does not influence clinical outcome. These data suggest prolonged fever should be avoided, but subfebrile temperatures may not justify intervention.

Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia.

PubMed

Boztug, Heidrun; Mühlegger, Nora; Pötschger, Ulrike; Attarbaschi, Andishe; Peters, Christina; Mann, Georg; Dworzak, Michael

2017-01-01

Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient's quality of life and decrease health care costs.

Risk-adapted approach for fever and neutropenia in paediatric cancer patients--a national multicentre study.

PubMed

Miedema, Karin G E; Tissing, Wim J E; Abbink, Floor C H; Ball, Lynne M; Michiels, Erna M C; van Vliet, Michel J; de Vries, Wilma Y; Kamps, Willem A; Norbruis, Obbe F; Fiocco, Marta; de Groot-Kruseman, Hester A; van de Wetering, Marianne D; de Bont, Eveline S J M

2016-01-01

In this national multicentre study, we examined the safety of reducing antibiotics in selected paediatric cancer patients with febrile neutropenia. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk and received antibiotic therapy. Remaining patients were allocated to low- or medium risk, depending on their interleukin-8 level. Low-risk patients did not receive any antibiotics and were discharged from the hospital after having been afebrile for 12 h. Medium-risk patients were re-evaluated after 72 h of antibiotic treatment and, in selected patients, antibiotics were stopped. Two hundred thirty-three febrile neutropenic episodes in 141 paediatric cancer patients were included in the study. Sixty-four episodes were classified high risk (28%), 122 medium risk (52%), and 47 (20%) low risk. In the medium-risk group, antibiotics were stopped after 72 h in 50 in 122 episodes (41%). Median duration of antibiotic treatment and hospital admission was significantly lower in low- and medium-risk episodes with early discharge. No failures were observed in the medium-risk group with early discharge. In the low-risk group, six failures were observed (12.8%), due to coagulase-negative staphylococci-positive blood cultures and recurrent fever. We showed that it is safe to shorten antibiotic treatment to 72 h in selected medium-risk patients with febrile neutropenia, regardless of the neutrophil count. The safety of withholding antibiotics in selected low-risk paediatric cancer patients with febrile neutropenia requires further investigation, using more suitable definitions for safety. Reduction in hospital admissions allows children with cancer more time at home and consequently improves their quality of life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validation of a case definition for leptospirosis diagnosis in patients with acute severe febrile disease admitted in reference hospitals at the State of Pernambuco, Brazil.

PubMed

Albuquerque Filho, Alfredo Pereira Leite de; Araújo, Jéssica Guido de; Souza, Inacelli Queiroz de; Martins, Luciana Cardoso; Oliveira, Marta Iglis de; Silva, Maria Jesuíta Bezerra da; Montarroyos, Ulisses Ramos; Miranda Filho, Demócrito de Barros

2011-01-01

Leptospirosis is often mistaken for other acute febrile illnesses because of its nonspecific presentation. Bacteriologic, serologic, and molecular methods have several limitations for early diagnosis: technical complexity, low availability, low sensitivity in early disease, or high cost. This study aimed to validate a case definition, based on simple clinical and laboratory tests, that is intended for bedside diagnosis of leptospirosis among hospitalized patients. Adult patients, admitted to two reference hospitals in Recife, Brazil, with a febrile illness of less than 21 days and with a clinical suspicion of leptospirosis, were included to test a case definition comprising ten clinical and laboratory criteria. Leptospirosis was confirmed or excluded by a composite reference standard (microscopic agglutination test, ELISA, and blood culture). Test properties were determined for each cutoff number of the criteria from the case definition. Ninety seven patients were included; 75 had confirmed leptospirosis and 22 did not. Mean number of criteria from the case definition that were fulfilled was 7.8±1.2 for confirmed leptospirosis and 5.9±1.5 for non-leptospirosis patients (p<0.0001). Best sensitivity (85.3%) and specificity (68.2%) combination was found with a cutoff of 7 or more criteria, reaching positive and negative predictive values of 90.1% and 57.7%, respectively; accuracy was 81.4%. The case definition, for a cutoff of at least 7 criteria, reached average sensitivity and specificity, but with a high positive predictive value. Its simplicity and low cost make it useful for rapid bedside leptospirosis diagnosis in Brazilian hospitalized patients with acute severe febrile disease.

Outpatient management of young febrile infants with urinary tract infections.

PubMed

Schnadower, David; Kuppermann, Nathan; Macias, Charles G; Freedman, Stephen B; Agrawal, Dewesh; Mao, Jingnan; Dayan, Peter S

2014-09-01

Controversy exists regarding the disposition of young febrile infants who present to emergency departments (EDs) with urinary tract infections (UTIs). In a large multicenter cohort of such patients, we aimed to determine the variation in patient disposition and clinical factors independently associated with outpatient management. Secondary analysis of a retrospective study of infants 29 to 60 days with fever (≥38.0°C), urinalysis finding, and culture-proven UTIs presenting to 20 North American EDs belonging to the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. We determined independent factors associated with outpatient management. Of 1764 infants with UTIs, 132 (7.5%) were discharged home from the ED. The proportion of infants managed as outpatients varied among sites (0%-20.0%). Of the 132 infants, 29 (22.0%) were subsequently hospitalized after culture results were known, including 5 patients with bacteremia. None of the 107 patients initially discharged from the ED for whom outcomes were known had adverse events (0%; 95% CI, 0%-2.7%). On multivariable regression and generalized estimated equations analyses, only clinical site, presence of upper respiratory tract infection symptoms, absence of vomiting, and having fewer than 10 white blood cells per microliter on cerebrospinal fluid examination were independently associated with discharge from the ED. Clinical site was the factor most highly associated with outpatient management (odds ratio, 8.8; 95% confidence interval, 5.2-15.0). There is substantial practice variation regarding the disposition of febrile infants 29 to 60 days of age with UTIs. Institutional practice is the strongest predictor of outpatient management. Further evidence is needed to guide the management of non-toxic-appearing young febrile infants with UTIs.

Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency.

PubMed

Sanna, M; Caocci, G; Orrù, F; Ledda, A; Vacca, A; Piras, E; Fozza, C; Deias, P; Tidore, G; Dore, F; La Nasa, G

2017-12-01

Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy-induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia. We retrospectively analysed 242 patients treated with 628 intensive chemotherapy courses. Of these, 59 patients were with G6PD-. All patients underwent fluoroquinolone prophylaxis and were transfused according to our single-unit transfusion policy. The principal endpoint was the incidence of acute haemolytic anaemia. Secondary endpoints included the incidence of febrile neutropenia, microbiologically and clinically documented infection (MDI and CDI) and the incidence of Gram-positive or Gram-negative infections. No episode of acute haemolytic anaemia was observed in the entire cohort. The incidence of MDI and CDI was similar, but the incidence of invasive fungal disease (IFD; P<.0001, HR 11.4, 95%CI 3.5-37.05) and Candida sepsis (P=.008, HR 37, 95%CI 2.01-680.9) was higher in patients with G6PD-. Interestingly, we observed a reduced incidence of febrile neutropenia in patients with G6PD- (P=.01, HR 0.46, 95%CI 0.25-0.8). Our data suggest that fluoroquinolone prophylaxis in patients with G6PD-, treated with intensive chemotherapy, is feasible and safe. Our findings on the incidence of IFD and febrile neutropenia suggest that G6PD may be important in susceptibility to opportunistic pathogens and host response in neutropenic patients. © 2017 John Wiley & Sons Ltd.

Three-day treatment with imipenem for unexplained fever during prolonged neutropaenia in haematology patients receiving fluoroquinolone and fluconazole prophylaxis: a prospective observational safety study.

PubMed

Slobbe, Lennert; Waal, Loes van der; Jongman, Lydia R; Lugtenburg, Pieternella J; Rijnders, Bart J A

2009-11-01

Guidelines advocate >7d of broad-spectrum antibiotics for unexplained fever (UF) during neutropaenia. However, effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. This study evaluates the safety of discontinuing empirical broad-spectrum antibiotics if no microbial source is documented after an initial work-up of 72 h. Prospective observational study at a tertiary-care haematology-unit in patients suffering from haematologic malignancies and treatment-induced prolonged neutropaenia of 10d. Oral fluoroquinolone and fluconazole prophylaxis was given from day 1. Fever was empirically treated with imipenem which was discontinued after 72 h if, following a standardised protocol, no infectious aetiology was documented. Duration of fever, antimicrobial therapy and overall mortality were registered. One hundred and sixty six patients were evaluated during 276 neutropaenic episodes. One hundred and thirty six patients (82.5%) experienced 1 febrile episode. A total of 317 febrile episodes were observed, of which 177 (56%) were diagnosed as UF. In 135 febrile episodes (43%), a probable/definite infectious origin was documented. Mean duration of fever in neutropaenic periods with 1 febrile episode was 5d, and mean time of treatment with imipenem was 4.7d. In patients without documented infection, mean time of imipenem treatment was only 3.7d. Overall mortality 30 d after neutrophil recovery was 3.6% (6/166); no patient died from untreated bacterial infection. Discontinuation of broad-spectrum antibiotics during neutropaenia in haematology patients on fluoroquinolone and fluconazole prophylaxis is safe, provided that no infectious aetiology is established after 72 h.

Accuracy of diagnosis codes to identify febrile young infants using administrative data.

PubMed

Aronson, Paul L; Williams, Derek J; Thurm, Cary; Tieder, Joel S; Alpern, Elizabeth R; Nigrovic, Lise E; Schondelmeyer, Amanda C; Balamuth, Fran; Myers, Angela L; McCulloh, Russell J; Alessandrini, Evaline A; Shah, Samir S; Browning, Whitney L; Hayes, Katie L; Feldman, Elana A; Neuman, Mark I

2015-12-01

Administrative data can be used to determine optimal management of febrile infants and aid clinical practice guideline development. Determine the most accurate International Classification of Diseases, Ninth Revision (ICD-9) diagnosis coding strategies for identification of febrile infants. Retrospective cross-sectional study. Eight emergency departments in the Pediatric Health Information System. Infants aged <90 days evaluated between July 1, 2012 and June 30, 2013 were randomly selected for medical record review from 1 of 4 ICD-9 diagnosis code groups: (1) discharge diagnosis of fever, (2) admission diagnosis of fever without discharge diagnosis of fever, (3) discharge diagnosis of serious infection without diagnosis of fever, and (4) no diagnosis of fever or serious infection. The ICD-9 diagnosis code groups were compared in 4 case-identification algorithms to a reference standard of fever ≥100.4°F documented in the medical record. Algorithm predictive accuracy was measured using sensitivity, specificity, and negative and positive predictive values. Among 1790 medical records reviewed, 766 (42.8%) infants had fever. Discharge diagnosis of fever demonstrated high specificity (98.2%, 95% confidence interval [CI]: 97.8-98.6) but low sensitivity (53.2%, 95% CI: 50.0-56.4). A case-identification algorithm of admission or discharge diagnosis of fever exhibited higher sensitivity (71.1%, 95% CI: 68.2-74.0), similar specificity (97.7%, 95% CI: 97.3-98.1), and the highest positive predictive value (86.9%, 95% CI: 84.5-89.3). A case-identification strategy that includes admission or discharge diagnosis of fever should be considered for febrile infant studies using administrative data, though underclassification of patients is a potential limitation. © 2015 Society of Hospital Medicine.

Accuracy of Diagnosis Codes to Identify Febrile Young Infants Using Administrative Data

PubMed Central

Aronson, Paul L.; Williams, Derek J.; Thurm, Cary; Tieder, Joel S.; Alpern, Elizabeth R.; Nigrovic, Lise E.; Schondelmeyer, Amanda C.; Balamuth, Fran; Myers, Angela L.; McCulloh, Russell J.; Alessandrini, Evaline A.; Shah, Samir S.; Browning, Whitney L.; Hayes, Katie L.; Feldman, Elana A.; Neuman, Mark I.

2015-01-01

Background Administrative data can be used to determine optimal management of febrile infants and aid clinical practice guideline development. Objective Determine the most accurate International Classification of Diseases, 9th revision (ICD-9) diagnosis coding strategies for identification of febrile infants. Design Retrospective cross-sectional study. Setting Eight emergency departments in the Pediatric Health Information System. Patients Infants age < 90 days evaluated between July 1, 2012 and June 30, 2013 were randomly selected for medical record review from one of four ICD-9 diagnosis code groups: 1) discharge diagnosis of fever, 2) admission diagnosis of fever without discharge diagnosis of fever, 3) discharge diagnosis of serious infection without diagnosis of fever, and 4) no diagnosis of fever or serious infection. Exposure The ICD-9 diagnosis code groups were compared in four case-identification algorithms to a reference standard of fever ≥ 100.4°F documented in the medical record. Measurements Algorithm predictive accuracy was measured using sensitivity, specificity, negative and positive predictive values. Results Among 1790 medical records reviewed, 766 (42.8%) infants had fever. Discharge diagnosis of fever demonstrated high specificity (98.2%, 95% confidence interval [CI]: 97.8-98.6) but low sensitivity (53.2%, 95% CI: 50.0-56.4). A case-identification algorithm of admission or discharge diagnosis of fever exhibited higher sensitivity (71.1%, 95% CI: 68.2-74.0), similar specificity (97.7%, 95% CI: 97.3-98.1), and the highest positive predictive value (86.9%, 95% CI: 84.5-89.3). Conclusions A case-identification strategy that includes admission or discharge diagnosis of fever should be considered for febrile infant studies using administrative data, though under-classification of patients is a potential limitation. PMID:26248691

Bias in medicine in the context of the film Aligarh.

PubMed

Sasi, Aiswarya

2017-01-01

In today's world, I feel another sin needs to be added to the list of the seven deadly sins, viz the sin of intolerance. We hear this term on the news every other day and see society display this attitude more often than not. While the movie Aligarh raised myriad social issues, as a medical student, I would like to speak of one in particular - the influence of stigma on healthcare.

Sin(x)**2 + cos(x)**2 = 1. [programming identities using comparative combinatorial substitutions

NASA Technical Reports Server (NTRS)

Stoutemyer, D. R.

1977-01-01

Attempts to achieve tasteful automatic employment of the identities sin sq x + cos sq x = 1 and cos sq h x -sin sq h x = 1 in a manner which truly minimizes the complexity of the resulting expression are described. The disappointments of trigonometric reduction, trigonometric expansion, pattern matching, Poisson series, and Demoivre's theorem are related. The advantages of using the method of comparative combinatorial substitutions are illustrated.

Destroying God's Temple? Physical Inactivity, Poor Diet, Obesity, and Other "Sin" Behaviors.

PubMed

Faries, Mark D; McClendon, Megan; Jones, Eric J

2017-02-17

On average, our participants (N = 112), who self-proclaimed to be Christians, believed that physically inactive lifestyles, unhealthy eating, overeating, and being obese destroy the body, God's temple. However, these beliefs were less definitive, than those of other common "sin" behaviors, such as drug use, smoking, and excessive drinking of alcohol. In addition, destroying the body with physical inactivity or poor diet was not necessarily viewed as sinful. Subsequently, these beliefs did not relate to self-reported physical activity, dietary behavior, or body mass index. It is possible that inactivity, poor dietary habits, and obesity are not internalized into the spiritual perspective as destroying the body, God's temple, in the same way as other "sin" behaviors.

Improved search for muon-neutrino to electron-neutrino oscillations in MINOS

DOE PAGES

Adamson, P.

2011-10-27

The authors report the results of a search for ν e appearance in ν μ beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2 x 10 20 protons on the NuMI target at Fermilab, they find that 2 sin 2 (θ 23 sin 2 (θ 13) < 0.12 (0.20) at 90% confidence level for δ = 0 and the normal (inverted) neutrino mass hierarchy, with a best fit of 2 sin 2θ 23) sin 2 (2θ 13) = 0.041 -0.031 +0.047 (0.079 -0.053 +0.071). The θ 13= 0 hypothesis is disfavored bymore » the MINOS data at the 89% confidence level.« less

Observation and modelling of main-sequence star chromospheres - XIV. Rotation of dM1 stars

NASA Astrophysics Data System (ADS)

Houdebine, E. R.

2010-09-01

We have measured v sin i for a selected sample of dM1-type stars. We give 114 measurements of v sin i for 88 different stars, and six upper detection limits. These are the first measurements of v sin i for most of the stars studied here. This represents the largest sample of v sin i measurements for M dwarfs at a given spectral type. For these measurements, we used four different spectrographs: HARPS (ESO), SOPHIE (OHP), ÉLODIE (OHP) and UVES (ESO). Two of these spectrographs (HARPS and SOPHIE) are particularly stable in wavelength since they were designed for exoplanet searches. We measured v sin i down to an accuracy of 0.3kms-1 for the highest resolution spectrographs and a detection limit of about 1kms-1. We show that this unprecedented accuracy for M dwarfs in our data set is possible because all the targets have the same spectral type. This is an advantage and it facilitates the determination of the narrowest line profiles for v sin i ~ 0. Although it is possible to derive the zero-point profiles using several spectral types at a time. These values were combined with other measurements taken from the literature. The total sample represents detected rotation for 100 stars (10 dM1e and 90 dM1 stars). We confirm our finding of Paper VII that the distribution of the projected rotation period is bimodal for dM1 stars with a much larger sample, i.e. there are two groups of stars: the fast rotators with P/sin i ~ 4.5d and the slow rotators with P/sin i ~ 14.4d. There is a gap between these two groups. We find that the distribution of stars as a function of P/sin i has two very abrupt cuts, below 10d and above 18d. There are very few stars observed out of this range 10-18d. We also observe that the distribution increases slightly from 18 to 10d. We find that the M1 subdwarfs (very low metallicity dwarfs) rotate with an average period of P/sin i ~ 7.2d, which is about twice faster as the main group of normal M1 dwarfs. We also find a correlation for P/sin i to decrease with stellar radius among dM1e stars. Such a trend is also observed in dM1 stars. We also derive metallicity and radius for all our target stars using the same method as in Paper VII. We notably found that 11 of our target stars are subdwarfs with metallicities below -0.5dex. Based on observations available at Observatoire de Haute Provence and the European Southern Observatory data bases and on Hipparcos parallax measurements. E-mail: eric_houdebine@yahoo.fr

Solar tidal variations of coefficients of second harmonic of gravitational potential of Mercury

NASA Astrophysics Data System (ADS)

Ferrandiz, Jose; Barkin, Yury

2010-05-01

Variations of coefficients of the second harmonic of Mercury potential caused by the solar tides have been studied. In the paper we use analytical expressions for tidal variations of Stoks coefficients obtained for model of the elastic celestial body with concentric distributions of masses and elastic parameters (Love numbers) and their reduced form with using fundamental elastic parameter k2 of the Mercury. Taking into account the resonant properties of the Mercury motion variations of the Mercury potential coefficients we present in the form of Fourier series on the multiple of corresponding arguments of the Mercury orbital theory. Evaluations of the amplitudes and periods of observed variations of Mercury potential have been tabulated for base elastic model of the Mercury characterized by hypothetic elastic parameter (Love number) k2=0.37 (Dehant et al., 2005). Tidal variations of polar moment of inertia of the Mercury (due to tidal deformations) lead to remarkable variations of the Mercury rotation. Tidal variations of the Mercury axial rotation also have been determined and tabulated. From our results it follows that the tide periodic variations of gravitational coefficients of the Mercury in a few orders bigger then corresponding tidal variations of Earth's geopotential coefficients (Ferrandiz, Getino, 1993). Variations coefficients of the second harmonic of Mercury potential. These variations are determined by the known formulae for variations of coefficients of the second harmonic of geopotential (Ferrandiz, Getino, 1993). Here we present these formulae in some special form as applied to the considered problem about the Mercury tidal deformations: ( ) δJ2 = - 3Tα23-2, δC22 = T α21 - α22 -4, δS22 = T α1α2-2, δC21 = Tα1α3, δS21 = T α2α3. Here T = k2(M R3 -ma3 ) = 1.667 × 10-7 is a estimation of some conditional coefficient of tidal deformation of Mercury. m and Rare the mass and the mean radius of Mercury. Here we have used standard values of ratio of mass of the Sun and Mercury m-M = 6023600, mean radius of Mercury R = 2439.7 km. a = 0.3870983098 AU is an unperturbed value of major semi-axis of Mercury orbit. k2=0.37. αjis direction cosines of the radius-vector of the Sun in Mercury principal axes of inertia. The central problem of the work was a construction of trigonometric developments of the producta and squares of these direction cosines multiplied on function(a-r)3, where r is a value of radius-vector of the Sun anda is a major semi-axis of orbit of Mercury (unperturbed value): (a-r)3αiαj. Omiting sufficiently long procedure on construction of developments for mentioned products we present final formulas for solar tidal variations of coefficients of Mercury gravitational potential: M--(R-)3Σ δJ2 = - 3k2m a [R0,ν(ρ,t)cos? ν + r0,ν(ρ,t)sin ?ν] ν ( ) 1 M-- R- 3Σ Σ [ (ɛ) (ɛ) ] δS22 = - 8k2m a R2,ν cos(2g +2l- ɛ? ν)- r2,ν sin (2g - ɛ?ν) , ν ɛ 1 M (R )3Σ Σ [ (ɛ) (ɛ) ] δC21 = - 4k2m- -a R1,ν cos (g + l- ɛ? ν)- r1,ν sin(g+ l- ɛ?ν) , ν ɛ ( )3Σ Σ [ ] δS21 = - 1 k2 M- R- R (ɛ1,)ν cos(g+ l- ɛ?ν)- r(1ɛ),ν sin(g- ɛ? ν). 4 m a ν ɛ For simplicity here we put the value of the angle ? = 00, that means that in unperturbed rotational motion of Mercury its vector of angular momentum consides with the polar principial axis of inertia. Here ɛ = ±1; ?ν are arguments located on multiple of mean longitudes of planets (Mercury, Venus, the Earth, Mars, Jupiter, Saturn, Uran and the Neptune): ?ν = ν1LMe + ν2LV + ν3LE + ν4LMa + ν5LJu + ν6LSa + ν7LUr + ν8LNe; ν = (ν1,ν2,ν3,...,ν8) are corresponding sets of integer indexes. Here all functions R and r are special inclination functions depending from angle ρof inclination of vector of angular momentum of Mercury with respect to normal to base (Laplace) plane and coefficients:Aν(j), Bν(j) and aν(j), bν(j): R0,ν(ρ,t) = - 1 (3 cos2ρ - 1)A(ν0)- 1sin2ρA(ν1)- 1sin2ρA(ν2), 6 2 4 1 ( ) 1 1 r0,ν(ρ,t) = -- 3cos2ρ- 1 a(ν0)- -sin2ρa(1ν)- - sin2 ρa(ν2), 6 2 4 ( ) R(1ɛ,ν)= sin 2ρ A (0ν)- 1A (2ν) - 2cos2ρA(ν1) + 2ɛ cos ρB(ν1) - ɛ sinρB (2ν), 2 ( 1 ) r(1ɛ,ν)= 2cosρb(ν1)- sinρb(2ν)- ɛsin2ρ a(0ν)- -a(ν2) + 2ɛcos2ρa(ν1), 2 (ɛ) ( 1 ) R2,ν = A(ν2)+ sin2ρ A(ν0)- 2A(ν2) - sin2ρA(ν1)+ 2ɛsinρB (ν1)+ ɛ cosρB (ν2), r2,ν(ɛ) = 2sinρbν(1) + cosρbν(2) - ɛaν(2) - ɛsin2ρ( (0) 1 (2)) aν - 2aν + ɛsin2ρaν(1) (ɛ = ±1). As particular case from our inclination functions of corresponding expression of Kinoshita's functions are obtained. In accordance with generalized Cassini-Colombo laws it inclination is evaluated as ρ= 2'1 on modern data of radiolocation of Mercury. First estimation of this parameter was about 1'6 (Barkin, 1984). Coefficients Aν(j), Bν(j) and aν(j), bν(j)with high accuracy have been presented as quadratic functions of the time which take into account secular planetary perturbations in the Mercury orbital motion (Kudrjavsev, 2009; Barkin, Kudrjavsev, Barkin, 2009): Aν(j) = Aν;0(j) + Aν;1(j) × t + Aν;2(j) × t2, A = (A,B,a,b), j = (0,1,2). These coefficients generalize similar Kinoshita's coefficients (in Earth rotation theory) and represent full and exact developments of following functions of heliocentric spherical coordinates of Mercury (r, φ and λ): 1( a)3(1 - 3sin2φ ) =Σ A(0)cos? +a(0)sin? , 2 r ν ν ν ν ν ( ) a-3cos2φ cos2 (λ - h) =Σ A (2)cos? ν + a(2)sin ?ν, r ν ν ν ( )3 Σ a- cos2φ sin2 (λ - h) = B (2ν)sin ?ν + b(ν2)cos?ν, r ν ( a)3 Σ -- sinφ cosφ sin (λ - h) = A (1ν)cos?ν + a(1ν)sin ?ν, r ν ( a)3 Σ (1) (1) r- sinφ cosφ cos(λ- h) = B ν sin?ν + bν cos?ν. ν The new expansions are valid over 2000 years, 1000AI 3000AD, have a form similar to that of Kinoshita's series. The latest long-term numerical ephemerides of the Moon and planets DE-406 are used as the source of disturbing bodies coordinates. The mentioned developments have been constructed not only for the problem about Mercury rotation but also for the problems about Earth rotation, Venus rotation and in theory of the Moon rotation (Kudrjavsev, 2009; Barkin, Kudrjavsev, Barkin, 2009). Corresponding developments of Kinoshita in the Earth rotation theory are obtained as particular case from above mentioned formulae by restricting conditions: r = a = b = 0. In the work we analize and evaluate amplitudes, frequencies and phases of solar tidal variations of coefficients of second harmonic of gravitational potential of Mercury. Also tidal perturbations of the Mercury axial rotation caused by variations of polar moment of inertia are determined and analized. The Barkin's work partially was financially accepted by Spanish grants, Japanese-Russian grant N-09-02-92113-JF and by RFBR grant N 08-02-00367.

Reconsidering the safety in numbers effect for vulnerable road users: an application of agent-based modeling.

PubMed

Thompson, Jason; Savino, Giovanni; Stevenson, Mark

2015-01-01

Increasing levels of active transport provide benefits in relation to chronic disease and emissions reduction but may be associated with an increased risk of road trauma. The safety in numbers (SiN) effect is often regarded as a solution to this issue; however, the mechanisms underlying its influence are largely unknown. We aimed to (1) replicate the SiN effect within a simple, simulated environment and (2) vary bicycle density within the environment to better understand the circumstances under which SiN applies. Using an agent-based modeling approach, we constructed a virtual transport system that increased the number of bicycles from 9% to 35% of total vehicles over a period of 1,000 time units while holding the number of cars in the system constant. We then repeated this experiment under conditions of progressively decreasing bicycle density. We demonstrated that the SiN effect can be reproduced in a virtual environment, closely approximating the exponential relationships between cycling numbers and the relative risk of collision as shown in observational studies. The association, however, was highly contingent upon bicycle density. The relative risk of collisions between cars and bicycles with increasing bicycle numbers showed an association that is progressively linear at decreasing levels of density. Agent-based modeling may provide a useful tool for understanding the mechanisms underpinning the relationships previously observed between volume and risk under the assumptions of SiN. The SiN effect may apply only under circumstances in which bicycle density also increases over time. Additional mechanisms underpinning the SiN effect, independent of behavioral adjustment by drivers, are explored.

Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation

PubMed Central

Nguyen, Minh Cong; Park, Jong Taek; Jeon, Yeong Gwan; Jeon, Byeong Hwa; Hoe, Kwang Lae; Kim, Young Myeong

2016-01-01

Purpose Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. Materials and Methods Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. Results SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. NG-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. Conclusion These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions. PMID:27593859

Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation.

PubMed

Nguyen, Minh Cong; Park, Jong Taek; Jeon, Yeong Gwan; Jeon, Byeong Hwa; Hoe, Kwang Lae; Kim, Young Myeong; Lim, Hyun Kyo; Ryoo, Sungwoo

2016-11-01

Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. N(G)-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions.

Lexical-Access Ability and Cognitive Predictors of Speech Recognition in Noise in Adult Cochlear Implant Users

PubMed Central

Smits, Cas; Merkus, Paul; Festen, Joost M.; Goverts, S. Theo

2017-01-01

Not all of the variance in speech-recognition performance of cochlear implant (CI) users can be explained by biographic and auditory factors. In normal-hearing listeners, linguistic and cognitive factors determine most of speech-in-noise performance. The current study explored specifically the influence of visually measured lexical-access ability compared with other cognitive factors on speech recognition of 24 postlingually deafened CI users. Speech-recognition performance was measured with monosyllables in quiet (consonant-vowel-consonant [CVC]), sentences-in-noise (SIN), and digit-triplets in noise (DIN). In addition to a composite variable of lexical-access ability (LA), measured with a lexical-decision test (LDT) and word-naming task, vocabulary size, working-memory capacity (Reading Span test [RSpan]), and a visual analogue of the SIN test (text reception threshold test) were measured. The DIN test was used to correct for auditory factors in SIN thresholds by taking the difference between SIN and DIN: SRTdiff. Correlation analyses revealed that duration of hearing loss (dHL) was related to SIN thresholds. Better working-memory capacity was related to SIN and SRTdiff scores. LDT reaction time was positively correlated with SRTdiff scores. No significant relationships were found for CVC or DIN scores with the predictor variables. Regression analyses showed that together with dHL, RSpan explained 55% of the variance in SIN thresholds. When controlling for auditory performance, LA, LDT, and RSpan separately explained, together with dHL, respectively 37%, 36%, and 46% of the variance in SRTdiff outcome. The results suggest that poor verbal working-memory capacity and to a lesser extent poor lexical-access ability limit speech-recognition ability in listeners with a CI. PMID:29205095

Investigation of Doppler Effects on the Detection of Polyphase Coded Radar Waveforms

DTIC Science & Technology

2003-02-01

wave2 = amp * sin(2*pi*two+(2*pi/7)); %the second modulated waveform %wave = [wavec wave1 wave2 wavec]; %the wave form put togther wave = amp...waveform wave1 = sin(2*pi*two+(pi/2)); %the first modulated waveform wave2 = sin(2*pi*two+(2*pi/7)); %the second modulated waveform...wave = [wavec wave1 wave2 wavec]; %the wave form put togther normval = max(abs(xcorr(wave,wave))); N=length

Modification of Light Emission in Si-Rich Silicon Nitride Films Versus Stoichiometry and Excitation Light Energy

NASA Astrophysics Data System (ADS)

Torchynska, T.; Khomenkova, L.; Slaoui, A.

2018-04-01

Si-rich SiN x films with different stoichiometry were grown on Si substrate by plasma-enhanced chemical vapor deposition. The Si content was varied by changing the NH3/SiH4 gas flow ratio from 0.45 up to 1.0. Conventional furnace annealing at 1100°C for 30 min was applied to produce the Si quantum dots (QDs) in the SiN x films. Spectroscopic ellipsometry was used to determine the refractive index of the SiN x films that allowed estimating the film's stoichiometry. Fourier transform infrared spectroscopy has been also used to confirm the stoichiometry and microstructure. Photoluminescence (PL) spectra of Si-rich SiN x films are complex. A non-monotonous variation of the different PL peaks versus Si excess contents testifies to the competition of different radiative channels. The analysis of PL spectra, measured at the different excitation light energies and variable temperatures, has revealed that the PL bands with the peaks within the range 2.1-3.0 eV are related to the carrier recombination via radiative native defects in the SiN x host. Simultaneously, the PL bands with the peaks at 1.5-2.0 eV are caused by the exciton recombination in the Si QDs of different sizes. The way to control the SiN x emission is discussed.

A Novel Grid SINS/DVL Integrated Navigation Algorithm for Marine Application

PubMed Central

Kang, Yingyao; Zhao, Lin; Cheng, Jianhua; Fan, Xiaoliang

2018-01-01

Integrated navigation algorithms under the grid frame have been proposed based on the Kalman filter (KF) to solve the problem of navigation in some special regions. However, in the existing study of grid strapdown inertial navigation system (SINS)/Doppler velocity log (DVL) integrated navigation algorithms, the Earth models of the filter dynamic model and the SINS mechanization are not unified. Besides, traditional integrated systems with the KF based correction scheme are susceptible to measurement errors, which would decrease the accuracy and robustness of the system. In this paper, an adaptive robust Kalman filter (ARKF) based hybrid-correction grid SINS/DVL integrated navigation algorithm is designed with the unified reference ellipsoid Earth model to improve the navigation accuracy in middle-high latitude regions for marine application. Firstly, to unify the Earth models, the mechanization of grid SINS is introduced and the error equations are derived based on the same reference ellipsoid Earth model. Then, a more accurate grid SINS/DVL filter model is designed according to the new error equations. Finally, a hybrid-correction scheme based on the ARKF is proposed to resist the effect of measurement errors. Simulation and experiment results show that, compared with the traditional algorithms, the proposed navigation algorithm can effectively improve the navigation performance in middle-high latitude regions by the unified Earth models and the ARKF based hybrid-correction scheme. PMID:29373549

Modification of Light Emission in Si-Rich Silicon Nitride Films Versus Stoichiometry and Excitation Light Energy

NASA Astrophysics Data System (ADS)

Torchynska, T.; Khomenkova, L.; Slaoui, A.

2018-07-01

Si-rich SiN x films with different stoichiometry were grown on Si substrate by plasma-enhanced chemical vapor deposition. The Si content was varied by changing the NH3/SiH4 gas flow ratio from 0.45 up to 1.0. Conventional furnace annealing at 1100°C for 30 min was applied to produce the Si quantum dots (QDs) in the SiN x films. Spectroscopic ellipsometry was used to determine the refractive index of the SiN x films that allowed estimating the film's stoichiometry. Fourier transform infrared spectroscopy has been also used to confirm the stoichiometry and microstructure. Photoluminescence (PL) spectra of Si-rich SiN x films are complex. A non-monotonous variation of the different PL peaks versus Si excess contents testifies to the competition of different radiative channels. The analysis of PL spectra, measured at the different excitation light energies and variable temperatures, has revealed that the PL bands with the peaks within the range 2.1-3.0 eV are related to the carrier recombination via radiative native defects in the SiN x host. Simultaneously, the PL bands with the peaks at 1.5-2.0 eV are caused by the exciton recombination in the Si QDs of different sizes. The way to control the SiN x emission is discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aaltonen, T.; Amerio, S.; Amidei, D.

Here, at the Fermilab Tevatron proton-antiproton (pmore » $$\\bar{p}$$) collider, Drell-Yan lepton pairs are produced in the process p$$\\bar{p}$$→e +e -+X through an intermediate γ*/Z boson. The forward-backward asymmetry in the polar-angle distribution of the e - as a function of the e +e --pair mass is used to obtain sin 2θ$$lept\\atop{eff}$$, the effective leptonic determination of the electroweak-mixing parameter sin2θW. The measurement sample, recorded by the Collider Detector at Fermilab (CDF), corresponds to 9.4 fb -1 of integrated luminosity from p$$\\bar{p}$$ collisions at a center-of-momentum energy of 1.96 TeV, and is the full CDF Run II data set. The value of sin 2θ$$lept\\atop{eff}$$ is found to be 0.23248±0.00053. The combination with the previous CDF measurement based on μ +μ - pairs yields sin 2θ$$lept\\atop{eff}$$=0.23221±0.00046. This result, when interpreted within the specified context of the standard model assuming sin 2θW=1-M$$2\\atop{W}$$/M$$2\\atop{Z}$$ and that the W- and Z-boson masses are on-shell, yields sin 2θW=0.22400±0.00045, or equivalently a W-boson mass of 80.328±0.024 GeV/c 2.« less

Efficient construction of producer cell lines for a SIN lentiviral vector for SCID-X1 gene therapy by concatemeric array transfection

PubMed Central

Throm, Robert E.; Ouma, Annastasia A.; Zhou, Sheng; Chandrasekaran, Anantharaman; Lockey, Timothy; Greene, Michael; De Ravin, Suk See; Moayeri, Morvarid; Malech, Harry L.; Sorrentino, Brian P.

2009-01-01

Retroviral vectors containing internal promoters, chromatin insulators, and self-inactivating (SIN) long terminal repeats (LTRs) may have significantly reduced genotoxicity relative to the conventional retroviral vectors used in recent, otherwise successful clinical trials. Large-scale production of such vectors is problematic, however, as the introduction of SIN vectors into packaging cells cannot be accomplished with the traditional method of viral transduction. We have derived a set of packaging cell lines for HIV-based lentiviral vectors and developed a novel concatemeric array transfection technique for the introduction of SIN vector genomes devoid of enhancer and promoter sequences in the LTR. We used this method to derive a producer cell clone for a SIN lentiviral vector expressing green fluorescent protein, which when grown in a bioreactor generated more than 20 L of supernatant with titers above 107 transducing units (TU) per milliliter. Further refinement of our technique enabled the rapid generation of whole populations of stably transformed cells that produced similar titers. Finally, we describe the construction of an insulated, SIN lentiviral vector encoding the human interleukin 2 receptor common γ chain (IL2RG) gene and the efficient derivation of cloned producer cells that generate supernatants with titers greater than 5 × 107 TU/mL and that are suitable for use in a clinical trial for X-linked severe combined immunodeficiency (SCID-X1). PMID:19286997

A Method for Oscillation Errors Restriction of SINS Based on Forecasted Time Series.

PubMed

Zhao, Lin; Li, Jiushun; Cheng, Jianhua; Jia, Chun; Wang, Qiufan

2015-07-17

Continuity, real-time, and accuracy are the key technical indexes of evaluating comprehensive performance of a strapdown inertial navigation system (SINS). However, Schuler, Foucault, and Earth periodic oscillation errors significantly cut down the real-time accuracy of SINS. A method for oscillation error restriction of SINS based on forecasted time series is proposed by analyzing the characteristics of periodic oscillation errors. The innovative method gains multiple sets of navigation solutions with different phase delays in virtue of the forecasted time series acquired through the measurement data of the inertial measurement unit (IMU). With the help of curve-fitting based on least square method, the forecasted time series is obtained while distinguishing and removing small angular motion interference in the process of initial alignment. Finally, the periodic oscillation errors are restricted on account of the principle of eliminating the periodic oscillation signal with a half-wave delay by mean value. Simulation and test results show that the method has good performance in restricting the Schuler, Foucault, and Earth oscillation errors of SINS.

A Method for Oscillation Errors Restriction of SINS Based on Forecasted Time Series

PubMed Central

Zhao, Lin; Li, Jiushun; Cheng, Jianhua; Jia, Chun; Wang, Qiufan

2015-01-01

Continuity, real-time, and accuracy are the key technical indexes of evaluating comprehensive performance of a strapdown inertial navigation system (SINS). However, Schuler, Foucault, and Earth periodic oscillation errors significantly cut down the real-time accuracy of SINS. A method for oscillation error restriction of SINS based on forecasted time series is proposed by analyzing the characteristics of periodic oscillation errors. The innovative method gains multiple sets of navigation solutions with different phase delays in virtue of the forecasted time series acquired through the measurement data of the inertial measurement unit (IMU). With the help of curve-fitting based on least square method, the forecasted time series is obtained while distinguishing and removing small angular motion interference in the process of initial alignment. Finally, the periodic oscillation errors are restricted on account of the principle of eliminating the periodic oscillation signal with a half-wave delay by mean value. Simulation and test results show that the method has good performance in restricting the Schuler, Foucault, and Earth oscillation errors of SINS. PMID:26193283

[Differential diagnosis of febrile exanthema].

PubMed

Aramă, St S; Anca, Ioana Alina; Munteanu, Daniela-Ioana; Aramă, Victoria; Hristea, Adriana; Moroti, Ruxandra; Ion, Daniela Adriana

2007-01-01

Febrile exanthema (FE) is an extremely polymorphous clinical entity, frequently seen in daily clinical practice. FE is characterized by diffuse rash and fever. FE is classified in 4 types, depending on the primary skin lesion: macular, maculopapular, vesicular, and bullous exanthema. It is of infectious and non-infectious cause. Among the infectious causes the most frequent is the viral one. FE may affect all ages, but especially children and young people. Usually, FE raises important issues of differential diagnosis, because its clinical and etiological complexity. To decide the most appropriate therapeutic and prophylactic measures for FE, it is important to know the clinical criteria and the specific diagnostic methods.

Undifferentiated febrile illnesses in military personnel.

PubMed

Burns, Daniel S; Bailey, Mark S

2013-09-01

Undifferentiated febrile illnesses (UFIs) present with acute symptoms, objective fever and no specific organ focus on clinical assessment. The term is mostly used in developing and tropical countries where a wide range of infections may be responsible. Laboratory diagnosis often requires specialist microbiology investigations that are not widely available, and serology tests that only become positive during convalescence. Optimal clinical management requires a good travel history, awareness of local endemic diseases, an understanding of the features that may help distinguish different causes and appropriate use of empirical antibiotics. This review describes the most common examples of UFI in military personnel on overseas deployments, and provides a practical approach to their initial management.