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Concept: Fever

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Background Acetaminophen is a common therapy for fever in patients in the intensive care unit (ICU) who have probable infection, but its effects are unknown. Methods We randomly assigned 700 ICU patients with fever (body temperature, ≥38°C) and known or suspected infection to receive either 1 g of intravenous acetaminophen or placebo every 6 hours until ICU discharge, resolution of fever, cessation of antimicrobial therapy, or death. The primary outcome was ICU-free days (days alive and free from the need for intensive care) from randomization to day 28. Results The number of ICU-free days to day 28 did not differ significantly between the acetaminophen group and the placebo group: 23 days (interquartile range, 13 to 25) among patients assigned to acetaminophen and 22 days (interquartile range, 12 to 25) among patients assigned to placebo (Hodges-Lehmann estimate of absolute difference, 0 days; 96.2% confidence interval [CI], 0 to 1; P=0.07). A total of 55 of 345 patients in the acetaminophen group (15.9%) and 57 of 344 patients in the placebo group (16.6%) had died by day 90 (relative risk, 0.96; 95% CI, 0.66 to 1.39; P=0.84). Conclusions Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days. (Funded by the Health Research Council of New Zealand and others; HEAT Australian New Zealand Clinical Trials Registry number, ACTRN12612000513819 .).

Concepts: Clinical trial, Statistics, Mathematics, Estimator, Intensive care medicine, Interquartile range, Placebo, Fever

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Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT ≥ 1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue.

Concepts: Malaria, Liver function tests, Aspartate transaminase, Alanine transaminase, Fever, Dengue fever, World Health Organization, EC 2.6.1

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The mosquito Aedes aegypti is one of the most important disease vectors because it transmits two major arboviruses, dengue and yellow fever, which cause significant global morbidity and mortality. Chemical insecticides form the cornerstone of vector control. The organophosphate temephos a larvicide recommended by WHO for controlling Ae. aegypti, however, resistance to this compound has been reported in many countries, including Brazil.

Concepts: Malaria, Mosquito, Yellow fever, Fever, Aedes aegypti, Aedes, Dengue fever, Insecticide

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Abstract. 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.

Concepts: Participation, Hospital, Blood type, Physician, Brucellosis, Fever, Blood culture, Received Pronunciation

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Genistein, the major isoflavone in soybean, was recently reported to exert beneficial effects in metabolic disorders and inflammatory diseases. In the present study, we investigated the effects and mechanisms of a dietary concentration of genistein on the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results demonstrated that genistein effectively inhibited the LPS-induced overproduction of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), as well as LPS-induced nuclear factor kappa B (NF-κB) activation. In addition, the data also showed that genistein prevented LPS-induced decrease in adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. These effects were obviously attenuated by an AMPK inhibitor. Taken together, our results suggest that the dietary concentration of genistein is able to attenuate inflammatory responses via inhibition of NF-κB activation following AMPK stimulation. The data provide direct evidence for the potential application of low concentrations of genistein in the prevention and treatment of inflammatory diseases.

Concepts: Immune system, Inflammation, Adenosine triphosphate, Interleukin, Enzyme inhibitor, Fever, Tumor necrosis factor-alpha, AMP-activated protein kinase

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The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, in part related to relatively small sample sizes. We set out to determine possible associations between dengue virus (DEN-V) NS3 specific T cells and cytokine and chemokine levels and the pathogenesis of severe disease in a large cohort of individuals with DHF.

Concepts: Immune system, DNA, Sample size, Virus, Ribavirin, Fever, Dengue fever, Dengue

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OBJECTIVES: To assess whether the flowcharts and discriminators of the Manchester Triage System (MTS) can be used as indicators of alarming signs of serious febrile illness to predict the risk of hospitalization for febrile children who present at the emergency department (ED). STUDY DESIGN: Observational study, which included 2455 children (<16 years) who came to the ED of a university hospital with fever as their main complaint (May 2007-July 2009). Alarming signs for serious febrile illness were matched with MTS flowcharts and discriminators. At triage, the percentage of alarming signs positive was calculated. The diagnostic ability of the percentage of alarming signs positive to identify children at risk of hospitalization was assessed by calculating positive and negative likelihood ratios. RESULTS: Thirty percent of children had at least 1 alarming sign positive at triage. Twenty-three percent were hospitalized. Positive likelihood ratios of hospitalization were 5.0 (95% CI: 3.9-6.5) for children with >20% of alarming signs positive at triage and 12.0 (95% CI: 5.2-27.6) for those with >40% of alarming signs positive. Negative likelihood ratios were 0.8 (95% CI: 0.8-0.8) and 1.0 (95% CI: 0.9-1.0), respectively. CONCLUSIONS: By alternatively using the flowcharts and discriminators of the MTS as alarming signs, rather than urgency classifiers, the MTS can function as a simple, readily available tool to identify febrile children at risk of hospitalization early in the care process. This knowledge may help to improve ED throughput times as well as admission and discharge management at pediatric EDs.

Concepts: Scientific method, Hospital, Fever, 0, Integer, Triage

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Background Zika virus (ZIKV) infection has been linked to the Guillain-Barré syndrome. From November 2015 through March 2016, clusters of cases of the Guillain-Barré syndrome were observed during the outbreak of ZIKV infection in Colombia. We characterized the clinical features of cases of Guillain-Barré syndrome in the context of this ZIKV infection outbreak and investigated their relationship with ZIKV infection. Methods A total of 68 patients with the Guillain-Barré syndrome at six Colombian hospitals were evaluated clinically, and virologic studies were completed for 42 of the patients. We performed reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays for ZIKV in blood, cerebrospinal fluid, and urine, as well as antiflavivirus antibody assays. Results A total of 66 patients (97%) had symptoms compatible with ZIKV infection before the onset of the Guillain-Barré syndrome. The median period between the onset of symptoms of ZIKV infection and symptoms of the Guillain-Barré syndrome was 7 days (interquartile range, 3 to 10). Among the 68 patients with the Guillain-Barré syndrome, 50% were found to have bilateral facial paralysis on examination. Among 46 patients in whom nerve-conduction studies and electromyography were performed, the results in 36 patients (78%) were consistent with the acute inflammatory demyelinating polyneuropathy subtype of the Guillain-Barré syndrome. Among the 42 patients who had samples tested for ZIKV by RT-PCR, the results were positive in 17 patients (40%). Most of the positive RT-PCR results were in urine samples (in 16 of the 17 patients with positive RT-PCR results), although 3 samples of cerebrospinal fluid were also positive. In 18 of 42 patients (43%) with the Guillain-Barré syndrome who underwent laboratory testing, the presence of ZIKV infection was supported by clinical and immunologic findings. In 20 of these 42 patients (48%), the Guillain-Barré syndrome had a parainfectious onset. All patients tested were negative for dengue virus infection as assessed by RT-PCR. Conclusions The evidence of ZIKV infection documented by RT-PCR among patients with the Guillain-Barré syndrome during the outbreak of ZIKV infection in Colombia lends support to the role of the infection in the development of the Guillain-Barré syndrome. (Funded by the Bart McLean Fund for Neuroimmunology Research and others.).

Concepts: Immune system, Cerebrospinal fluid, Fever, Dengue fever, The Onset, Chronic inflammatory demyelinating polyneuropathy, 2016, 2015

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BACKGROUND: Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. METHODS: Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive “gold standard” (ANC <1.0x109/L, and body temperature >=38.30C or receipt of antibiotics) and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity. RESULTS: Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24–45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78–95) and sensitivity was 57% (46–68). For the definition including neutropenia in any position (n=71), PPV was 77% (68–87) and sensitivity was 67% (56–77). CONCLUSIONS: Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases–with an acceptable level of mis-classification–using diagnosis codes for neutropenia, or neutropenia plus fever.

Concepts: Medicine, Health insurance, Positive predictive value, Negative predictive value, Thermoregulation, Hyperthermia, Fever, Febrile neutropenia

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Early diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection.

Concepts: Inflammation, Cohort study, Epidemiology, Clinical trial, Myocardial infarction, Medical terms, Hospital, Fever