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INTRODUCTION: Febrile infants under 3 months of age are at risk of invasive bacterial infection (IBI). It is currently unclear if testing for respiratory viruses may have a role in IBI risk stratification. If found to be associated with the likelihood of IBI, respiratory viral point-of-care testing may improve patient and caregiver experience, reduce costs and enhance antimicrobial stewardship. METHODS AND ANALYSIS: This is a study protocol for a systematic review and meta-analysis that aims to answer the following question: In young febrile infants presenting to emergency care settings does a positive respiratory viral test for RSV, Influenza or SARS-CoV2 (relative to a negative test) add value to current risk stratification pathways for the exclusion of invasive bacterial infection, subsequently enabling safe de-escalation of investigation and treatment?A search strategy will include MEDLINE, EMBASE, Web of Science, The Cochrane Library and grey literature. Abstracts and then full texts will be independently screened for selection. Data extraction and quality assessment will be completed by two independent authors.The primary objective is to analyse the ability of a positive respiratory viral test to identify the overall risk of IBI. The secondary objective is to perform a subgroup analysis to investigate how the risk stratification alters based on other variables including virus type, patient characteristics and the presence of an identified source of fever.Bivariate random-effects meta-analysis will be undertaken. Diagnostic odds ratios (OR), sensitivity, specificity and positive and negative likelihood ratios will be calculated. The degree of heterogeneity and publication bias will be investigated and presented. ETHICS AND DISSEMINATION: Ethical approval is not required. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through publication and conference presentations. PROSPERO REGISTRATION NUMBER: This protocol is registered in PROSPERO-ID number: CRD42023433716.
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Fiebre , Humanos , Lactante , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , COVID-19/diagnóstico , Fiebre/diagnóstico , Fiebre/virología , Gripe Humana/diagnóstico , Gripe Humana/virología , Metaanálisis como Asunto , Pruebas en el Punto de Atención , Proyectos de Investigación , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/virología , Medición de Riesgo/métodos , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous and complex blood cancer requiring aggressive treatment. Early identification and prediction of the complications following treatment is vital for effective disease management. AIMS: We explored associations between plasma protein levels and fever- and infection-related complications in 26 AML patients during chemotherapy-induced neutropenia. MATERIAL AND METHODS: Longitudinal plasma profiling was conducted using data-dependent mass spectrometry analysis. RESULTS: Mass spectrometry-based plasma profiling data correlated well with laboratory parameters, including C-reactive protein, and revealed a broader inflammation protein network associated with fever- and infection-related complications. DISCUSSION AND CONCLUSION: These data indicate the potential of longitudinal plasma profiling in AML patients for identifying and predicting complications that may aid in improved disease monitoring and treatment.
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Fiebre , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Fiebre/inducido químicamente , Fiebre/sangre , Fiebre/diagnóstico , Neutropenia/inducido químicamente , Neutropenia/sangre , Neutropenia/diagnóstico , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Neutropenia Febril Inducida por Quimioterapia/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Longitudinales , Infecciones/sangre , Infecciones/diagnóstico , Proteína C-Reactiva/análisis , Adulto JovenRESUMEN
After the COVID-19 pandemic, fever clinics urgently require rapid nucleic acid tests to enhance their capacity for timely pathogen detection. This study evaluated the analytical performance and clinical utility of the Flash10 SARS-CoV-2 point-of-care test (Flash10 POCT) for detecting SARS-CoV-2 in patients with fever in the adult fever clinic in Beijing Tsinghua Changgung Hospital from August 1 to August 30, 2023. The analytical performance and clinical utility of the Flash10 POCT for detecting SARS-CoV-2 were assessed in 125 patients with fever syndrome in the adult fever clinic. The Flash10 POCT demonstrated an analytical precision of 3.1% for the Ct values of the ORF1ab gene and 2.9% for the Ct values of the N gene in SARS-CoV-2 nucleic acid testing. Furthermore, the Flash10 POCT demonstrated a lower limit of detection (LoD) of 100 copies/mL, with no detected aerosol contamination leakage. Of the 125 patients (median age 61.9 years, 52% male and 48% female), both the Flash10 POCT and RT-PCR tests yielded positive results for 100 patients and negative results for 25 patients (Fisher's exact test, p < 0.0001). The median turn-around-time for the Flash10 POCT was significantly shorter, at 1.05 h, compared to 16.15 h required for RT-PCR tests (Wilcoxon signed rank test, p < 0.0001). The Flash10 POCT showed high analytical performance, achieving a 100% detection rate for SARS-CoV-2 compared to RT-PCR tests, while also exhibiting a significantly shorter turn-around-time. Implementing the Flash10 POCT had the potential to expedite the care of adults presenting with fever.
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COVID-19 , Pruebas en el Punto de Atención , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/virología , Femenino , Masculino , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Persona de Mediana Edad , Anciano , Adulto , Sistemas de Atención de Punto , Prueba de Ácido Nucleico para COVID-19/métodos , Sensibilidad y Especificidad , Límite de Detección , Anciano de 80 o más Años , Fiebre/diagnóstico , Fiebre/virología , ARN Viral/genética , Proteínas Virales , PoliproteínasRESUMEN
Night sweats are a common symptom. There is a lack of a uniform definition and a diagnostic guideline. In this article we propose a structural analysis for all levels of healthcare. First, we need to distinguish night sweats with or without fever. We will then discuss the main differential diagnoses (infection, malignancies, sleeping disorders and medication-related) and emphasize the role of diagnostic clues. A screening for infections, sleeping disorders and a medication review are a must for every patient. Furthermore we will explain the role of PET-CT and bone marrow examination.
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Sudoración , Humanos , Diagnóstico Diferencial , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/etiología , Neoplasias/diagnóstico , Fiebre/etiología , Fiebre/diagnóstico , Infecciones/diagnósticoRESUMEN
Background & objectives Q fever is an important zoonotic disease affecting humans as well as animals. The objective of this study was to assess the burden of Q fever in individuals with acute febrile illness, particularly those in close contact with animals. Various diagnostic methods were also evaluated in addition to clinical examination analysis and associated risk factors. Methods Individuals presenting with acute febrile illness who had animal exposure were enrolled (n=92) in this study. Serum samples were tested using IgG and IgM phase 2 enzyme linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). The PCR targeting the com1 and IS1111 genes was performed on blood samples. PCR amplicons were sequenced and phylogenetically analysed. Demographic data, symptoms, and risk factors were collected through a structured questionnaire. Results Among individuals with acute febrile illness, 34.7 per cent (32 out of 92) were found to be infected with Coxiella burnetii. PCR exhibited the highest sensitivity among the diagnostic methods employed. The most common clinical manifestations included headache, chills, arthralgia, and fatigue. Individuals engaged in daily livestock-rearing activities were found to be at an increased risk of infection. Interpretation & conclusions Q fever is underdiagnosed due to its varied clinical presentations, diagnostic complexities, and lack of awareness. This study underscores the importance of regular screening for Q fever in individuals with acute febrile illness, particularly those with animal exposure. Early diagnosis and increased awareness among healthcare professionals are essential for the timely management and prevention of chronic complications associated with Q fever.
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Coxiella burnetii , Fiebre , Fiebre Q , Fiebre Q/diagnóstico , Fiebre Q/sangre , Fiebre Q/complicaciones , Fiebre Q/epidemiología , Humanos , Animales , Coxiella burnetii/patogenicidad , Coxiella burnetii/aislamiento & purificación , Masculino , Adulto , Femenino , Fiebre/microbiología , Fiebre/diagnóstico , Persona de Mediana Edad , Animales Domésticos/microbiología , Zoonosis/microbiología , Zoonosis/diagnóstico , Zoonosis/sangre , Factores de Riesgo , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Adolescente , Ganado/microbiología , Enfermedad AgudaAsunto(s)
Fiebre , Ictericia , Leptospirosis , Mialgia , Insuficiencia Respiratoria , Adulto , Humanos , Masculino , Diagnóstico Diferencial , Fiebre/diagnóstico , Fiebre/tratamiento farmacológico , Fiebre/microbiología , Ictericia/diagnóstico , Ictericia/tratamiento farmacológico , Ictericia/microbiología , Pulmón/diagnóstico por imagen , Pulmón/patología , Mialgia/diagnóstico , Mialgia/tratamiento farmacológico , Mialgia/microbiología , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/microbiología , Tomografía Computarizada por Rayos X , Hígado/microbiología , Hígado/patología , Biopsia , Leptospira/aislamiento & purificación , Leptospirosis/complicaciones , Leptospirosis/diagnóstico , Leptospirosis/tratamiento farmacológico , Leptospirosis/microbiología , Resultado del Tratamiento , Doxiciclina/administración & dosificaciónRESUMEN
New American Academy of Pediatrics (AAP) guidelines were published in 2021 for the evaluation and management of well-appearing febrile infants from age 8 to 60 days. This first guideline of its kind from the AAP brings together increasing evidence from the last 20 years and replaces the varied protocols previously used (eg, Rochester, Philadelphia, Boston). The guideline also incorporates lessons from newer studies, such as the work of the Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network. This article will explain the motivation for the guideline, summarize its recommendations, and fill in some details about how to evaluate and manage infants that fall out of the guideline's scope of the well-appearing febrile infant age 8 to 60 days (ill-appearing infants and early-onset infections in newborns younger than age 8 days). [Pediatr Ann. 2024;53(9):e314-e319.].
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Fiebre , Humanos , Lactante , Recién Nacido , Fiebre/etiología , Fiebre/terapia , Fiebre/diagnóstico , Guías de Práctica Clínica como Asunto , Pediatría/métodosRESUMEN
OBJECTIVE: Emergency physicians are always faced with the challenge of choosing the appropriate disposition for elderly patients in order to ensure an acceptable care plan and effective use of resources. A clinical decision rule, Geriatric Fever Score (GFS) has been proposed but not validated to help ED physicians with decision-making. This rule employs leukocytosis, severe coma, and thrombocytopenia as predictors of 30-day mortality. Through our study determines the performance of this clinical prediction rule in a prospective study in a setting different from where it was developed. METHOD AND MATERIALS: In this prospective cohort study in a 1200-bed tertiary care, patients older than 65 years old who visited the ED with fever were enrolled. All elements of the rule were collected and the total score was calculated for each patient. Patients were also categorized as low risk (score 0-1) or high risk (score ≥ 2). Thirty-day follow-up was performed to determine the patient outcome (survival or mortality). RESULTS: A total of 296 patients were included in our final analysis. The mortality rate was 33.1% for patients with a Score of 0, 42.1% for a score of 1, 57.1% for a score of 2, and 100% for a score of 3. When divided into two risk groups, patients' mortality rates were as follows: low risk group 37.9% and high-risk group 40.5%. CONCLUSION: Our study showed that elderly patients who present to ED with fever and have a score of 2 or higher on the Geriatric Fever Score are at higher risk of mortality at 30 days.
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Servicio de Urgencia en Hospital , Fiebre , Humanos , Anciano , Estudios Prospectivos , Masculino , Femenino , Fiebre/mortalidad , Fiebre/diagnóstico , Anciano de 80 o más Años , Evaluación Geriátrica/métodos , Reglas de Decisión Clínica , Estudios de Cohortes , Valor Predictivo de las Pruebas , Pronóstico , Mortalidad Hospitalaria/tendenciasRESUMEN
INTRODUCTION: Protracted febrile myalgia syndrome (PFMS) is a rare manifestation of familial Mediterranean fever (FMF), characterized by myalgia, fever and elevated inflammatory markers lasting several weeks. As the hallmark of FMF are short episodes of disease symptoms, the long duration of PFMS may lead to a delayed diagnosis and treatment. OBJECTIVES: 1. To perform a review of literature and rheumatology textbooks focused on clinical features and treatment of PFMS in children. 2. To present our own case. METHODS: All articles in Pub Med generated using the keywords "protracted febrile myalgia" and information on PFMS in seven rheumatology textbooks were collected. The systematic review was supplemented with our own case presentation. RESULTS: In total, 18 articles with 78 pediatric patients (including our own) were retrieved. More than half of the patients presented with PFMS as the first manifestation of FMF. All complained of myalgia, 65% of abdominal pain and 26% had a rash. Corticosteroids (CS) were effective in 77%. In all CS-refractory cases, anakinra was shown efficient. MRI was used in 5 patients and showed myositis in all of them. The scrutiny of seven rheumatology textbooks showed that PFMS presenting with myalgia was mentioned in six. Possible accompanying symptoms were described only once, the long duration of symptoms twice, the efficacy of corticosteroids three times and anakinra only once. The presented 6 year old patient manifested with fever, myalgia, abdominal pain and petechial rash lasting 6 weeks. She had undergone multiple diagnostic procedures before her parents mentioned a positive family history for FMF. The subsequent genetic testing confirmed a homozygosity for M694V pathogenic variant in the MEFV gene. CONCLUSION: The long duration of PFMS may be misleading to clinicians especially if PFMS occurs at manifestation of FMF. The fact that more than half of the reported patients experienced PFMS as the presenting symptom of FMF is one of the key findings of our study. Our case presentation demonstrates the importance of genetic testing early in suspected autoinflammatory diseases. Furthermore, MRI may be an important diagnostic tool showing myositis in PFMS.
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Fiebre Mediterránea Familiar , Fiebre , Mialgia , Niño , Humanos , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/diagnóstico , Fiebre/diagnóstico , Fiebre/etiología , Imagen por Resonancia Magnética/métodos , Mialgia/diagnóstico , Mialgia/etiología , SíndromeAsunto(s)
Amiloidosis , Artritis Reumatoide , Edema , Nefritis Lúpica , Proteinuria , Anciano , Femenino , Humanos , Diagnóstico Diferencial , Edema/diagnóstico , Edema/tratamiento farmacológico , Edema/etiología , Riñón/patología , Riñón/diagnóstico por imagen , Proteinuria/diagnóstico , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Dolor Abdominal/diagnóstico , Dolor Abdominal/etiología , Fiebre/diagnóstico , Fiebre/etiología , Mano/diagnóstico por imagen , Biopsia con Aguja Gruesa , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/patología , Amiloidosis/sangre , Amiloidosis/diagnóstico , Amiloidosis/tratamiento farmacológico , Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Proteína Amiloide A Sérica/análisisRESUMEN
BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).
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Fiebre , Nairovirus , Mordeduras de Garrapatas , Adulto , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Adulto Joven , Anticuerpos Antivirales/sangre , China/epidemiología , Fiebre/diagnóstico , Fiebre/epidemiología , Fiebre/virología , Nairovirus/genética , Nairovirus/aislamiento & purificación , Nairovirus/patogenicidad , Filogenia , Mordeduras de Garrapatas/complicaciones , Mordeduras de Garrapatas/virología , Prevalencia , Modelos Animales de Enfermedad , Ovinos , Caballos , Porcinos , Lactante , Preescolar , Niño , Adolescente , Anciano de 80 o más AñosAsunto(s)
Influenza Pandémica, 1918-1919 , Gripe Humana , Neumonía Viral , Humanos , Masculino , Adulto Joven , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Diagnóstico Diferencial , Disnea/diagnóstico , Disnea/etiología , Pulmón/diagnóstico por imagen , Pulmón/patología , Radiografía Torácica , Fiebre/diagnóstico , Fiebre/etiología , Tos/diagnóstico , Tos/etiología , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Influenza Pandémica, 1918-1919/historia , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Historia del Siglo XX , Historia del Siglo XXI , Monitoreo Epidemiológico , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Preparación para una Pandemia , Vacunas contra la Influenza/administración & dosificaciónRESUMEN
OBJECTIVE: In this observational study, we determined the distribution of mHealth applications (apps) in Germany using data from the FeverApp registry. METHODS: The registry data were processed to assess general monthly trends in app distribution, and a seasonal autoregressive integrated moving average model was decomposed to investigate time series. A sample comparison was made matching data from cold-called against self-registered distributers of the FeverApp. RESULTS: Among 881 pediatric and adolescent medical practices, 27,300 app users were recruited between 2019 and August 2023. The number of monthly recruited users increased steadily. A seasonal trend was observed, showing a higher distribution in winter months. Self-registered pediatric practices did not recruit significantly more app users than cold-called practices, with approximately every 25th family recruited in both groups. CONCLUSIONS: The trend of more app sign-ups during winter is likely related to the flu season in Germany. Intrinsic and extrinsic motivational factors of the practices seem to have a large impact on the distribution. We observed a positive trend in the app distribution. Seasonal febrile infections and individual distribution methods among practices influence the distribution of the FeverApp in Germany. Family factors may have a greater influence than the motivation of distributing practices.
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Aplicaciones Móviles , Sistema de Registros , Telemedicina , Humanos , Alemania/epidemiología , Adolescente , Niño , Femenino , Masculino , Estaciones del Año , Fiebre/epidemiología , Fiebre/diagnósticoRESUMEN
Metagenomic next generation metagenomic sequencing (mNGS) has proven to be a useful tool in the diagnosis and identification of novel human pathogens and pathogens not identified on routine clinical microbiologic tests. In this study, we applied mNGS to characterize plasma RNA isolated from 42 study participants with unexplained acute febrile illness (AFI) admitted to tertiary referral hospitals in Mubende and Arua, Uganda. Study participants were selected based on clinical criteria suggestive of viral infection (i.e., thrombocytopenia, leukopenia). The study population had a median age of 28 years (IQR:24 to 38.5) and median platelet count of 114 x103 cells/mm3 (IQR:66,500 to 189,800). An average of 25 million 100 bp reads were generated per sample. We identified strong signals from diverse virus, bacteria, fungi, or parasites in 10 (23.8%) of the study participants. These included well recognized pathogens like Helicobacter pylori, human herpes virus-8, Plasmodium falciparum, Neisseria gonorrhoeae, and Rickettsia conorii. We further confirmed Rickettsia conorii infection, the cause of Mediterranean Spotted Fever (MSF), using PCR assays and Sanger sequencing. mNGS was a useful addition for detection of otherwise undetected pathogens and well-recognized non-pathogens. This is the first report to describe the molecular confirmation of a hospitalized case of MSF in sub-Saharan Africa (SSA). Further studies are needed to determine the utility of mNGS for disease surveillance in similar settings.
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Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Humanos , Uganda/epidemiología , Adulto , Metagenómica/métodos , Femenino , Masculino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adulto Joven , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Virus/genética , Virus/aislamiento & purificación , Virus/clasificación , Virosis/diagnóstico , Virosis/sangre , Virosis/virología , Fiebre de Origen Desconocido/diagnóstico , Fiebre/diagnósticoAsunto(s)
Fiebre , Guías de Práctica Clínica como Asunto , Polipéptido alfa Relacionado con Calcitonina , Humanos , Polipéptido alfa Relacionado con Calcitonina/sangre , Lactante , Fiebre/etiología , Fiebre/diagnóstico , Mejoramiento de la Calidad , Recién Nacido , Biomarcadores/sangre , Femenino , Masculino , Antibacterianos/uso terapéuticoRESUMEN
Guidelines advocate that the symptomatic management of fever should prioritize alleviating the child's discomfort. We investigated the definition and assessment of discomfort in febrile children within the scientific pediatric literature. A systematic review was conducted in accordance with PRISMA 2020 guidelines and preregistered on the Prospero database (CRD42023471590). Databases including PubMed, Embase, and Cochrane were searched. Studies addressing discomfort in febrile children were eligible. Out of 794 initially identified articles, 27 original studies and seven guidelines specifically used the term 'discomfort'. Only 14 original articles provided a definition of discomfort, revealing substantial heterogeneity and no clear-cut definition. Discomfort was often assessed subjectively, predominantly through parent or self-report, and only two studies used a scoring system for assessment. The definitions varied widely, with terms such as crying, irritability, shivering and chills, pain and distress, goosebumps commonly used and evaluation of observable modifications such as facial modifications. Overall, no consensus on a single, standardized definition was available. CONCLUSIONS: This systematic review shows the absence of a standardized definition and assessment of discomfort in febrile children. The findings of the present analysis might be the basis for building a consensus and developing a new tool to evaluate discomfort. WHAT IS KNOWN: ⢠Discomfort is currently considered the main criterion to guide antipyretic administration in children with fever. ⢠Despite this clear-cut recommendation, it has been questioned whether a commonly accepted understanding and assessment of this condition exists. WHAT IS NEW: ⢠This systematic review identifies a significant heterogeneity in definitions and assessment of discomfort in children with fever. ⢠Both subjective parameters and observable modifications in physiological parameters should be included in a new and shared characterization of discomfort.
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Fiebre , Humanos , Fiebre/diagnóstico , Fiebre/etiología , Niño , Antipiréticos/uso terapéutico , Dolor/etiología , Dolor/diagnóstico , PreescolarRESUMEN
Importance: A prompt malaria diagnosis is crucial for the management of children with febrile illness in sub-Saharan African countries, where malaria remains a leading cause of mortality among children younger than 5 years of age. The development and distribution of point-of-care rapid diagnostic tests (RDTs) for malaria has transformed practice, but limited systematic evidence exists on how malaria RDTs have affected the management of febrile illness and mortality for children younger than 5 years of age across sub-Saharan Africa countries. Objective: To evaluate the association between the distribution of malaria RDTs and the management of febrile illness and mortality among children younger than 5 years of age in sub-Saharan African countries. Design, Setting, and Participants: This quasi-experimental study used a novel dataset linking malaria RDT distribution to 165 nationally representative household surveys across 35 sub-Saharan African countries with mortality data. The sample comprised approximately 3.9 million child-year observations and approximately 260â¯000 febrile illness episodes in children younger than 5 years of age between 2000 and 2019. Main Outcomes and Measures: Fixed-effects linear probability models were used to analyze the association between variation in malaria RDTs distributed per child younger than 5 years of age (by country per year) and blood testing, antimalarial drug use, antibiotic use, use of symptomatic treatments, and mortality rates. Variation in the effects of testing and treatment was also assessed across the sub-Saharan African countries that had varying prevalence of malaria. Results: The mortality sample included 1â¯317â¯866 children and the fever sample included 256â¯292 children. The mean age of the children with febrile illness was 2.4 years (SD, 1.3 years) and 49% were female. Each additional malaria RDT distributed per child younger than 5 years of age was associated with an increase of 3.5 percentage points (95% CI, 3.2-3.8 percentage points) in blood testing, an increase of 1.5 percentage points (95% CI, 1.2-1.8 percentage points) in the use of antimalarial drugs, an increase of 0.4 percentage points (95% CI, 0.1-0.6 percentage points) in antibiotic use, and a decrease of 0.4 percentage points (95% CI, 0.1-0.8 percentage points) in the use of treatments for symptoms. Each additional malaria RDT distributed per child younger than 5 years of age was associated with a reduction in child mortality of 0.34 deaths per 1000 child-years (95% CI, 0.15-0.52 deaths per 1000 child-years). The effects of malaria RDT distribution on medication use and child mortality varied across prevalence settings (low vs high) for malaria; there were survival improvements only in areas that had a high prevalence of malaria. Conclusions and Relevance: Increasing distribution of malaria RDTs was associated with increased blood testing, increased use of antimalarial drugs, and modestly improved survival in children younger than 5 years of age in sub-Saharan African countries. However, malaria RDTs were associated with increases in the rates of antibiotic use that were already high, suggesting that more comprehensive approaches to case management of febrile illness are needed.
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Mortalidad del Niño , Fiebre , Malaria , Preescolar , Femenino , Humanos , Lactante , Masculino , África del Sur del Sahara/epidemiología , Antimaláricos/uso terapéutico , Mortalidad del Niño/tendencias , Pruebas Diagnósticas de Rutina , Fiebre/diagnóstico , Fiebre/tratamiento farmacológico , Fiebre/etiología , Fiebre/mortalidad , Malaria/complicaciones , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/mortalidad , Pruebas en el Punto de Atención , Recién Nacido , Prueba de Diagnóstico Rápido , Diagnóstico Diferencial , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia BacterianaAsunto(s)
Antimaláricos , Fiebre , Malaria , Pruebas en el Punto de Atención , Humanos , Antígenos de Protozoos/genética , Antígenos de Protozoos/aislamiento & purificación , Antimaláricos/uso terapéutico , Fiebre/diagnóstico , Fiebre/tratamiento farmacológico , Fiebre/parasitología , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/mortalidad , Malaria/parasitología , Cumplimiento de la Medicación , Plasmodium falciparum/genética , Plasmodium falciparum/aislamiento & purificación , Plasmodium vivax/genética , Plasmodium vivax/aislamiento & purificación , Resultado del Tratamiento , Prueba de Diagnóstico RápidoRESUMEN
BACKGROUND: Whole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression. METHODS: We validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment. We included a novel 3-transcript signature for childhood tuberculosis, and four published signatures which differentiate bacterial infection, viral infection, or Kawasaki disease from other febrile illnesses. Signature performance was assessed using receiver operating characteristic curve statistics. We also explored conceptual frameworks for multiclass diagnostic signatures, including additional transcripts found to be significantly differentially expressed in previous studies. Relaxed, regularised logistic regression models were used to derive two novel multiclass signatures: a mixed One-vs-All model (MOVA), running multiple binomial models in parallel, and a full-multiclass model. In-sample performance of these models was compared using radar-plots and confusion matrix statistics. RESULTS: Samples from 91 children were included in the study: 23 bacterial infections (DB), 20 viral infections (DV), 14 Kawasaki disease (KD), 18 tuberculosis disease (TB), and 16 healthy controls. The five signatures tested demonstrated cross-platform performance similar to their primary discovery-validation cohorts. The signatures could differentiate: KD from other diseases with area under ROC curve (AUC) of 0.897 [95% confidence interval: 0.822-0.972]; DB from DV with AUC of 0.825 [0.691-0.959] (signature-1) and 0.867 [0.753-0.982] (signature-2); TB from other diseases with AUC of 0.882 [0.787-0.977] (novel signature); TB from healthy children with AUC of 0.910 [0.808-1.000]. Application of signatures outside of their designed context reduced performance. In-sample error rates for the multiclass models were 13.3% for the MOVA model and 0.0% for the full-multiclass model. The MOVA model misclassified DB cases most frequently (18.7%) and TB cases least (2.7%). CONCLUSIONS: Our study demonstrates the feasibility of NanoString technology for cross-platform validation of multiple transcriptomic signatures in parallel. This external cohort validated performance of all five signatures, including a novel sparse TB signature. Two exploratory multi-class models showed high potential accuracy across four distinct diagnostic groups.
Asunto(s)
Fiebre , Tuberculosis , Humanos , Tuberculosis/diagnóstico , Tuberculosis/genética , Niño , Fiebre/diagnóstico , Fiebre/microbiología , Preescolar , Femenino , Masculino , Curva ROC , Perfilación de la Expresión Génica , Reproducibilidad de los Resultados , Lactante , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Mensajero/sangre , Transcriptoma/genéticaRESUMEN
BACKGROUND: Neurosarcoidosis is a rare entity, usually within the context of systematic sarcoidosis. Isolated neurosarcoidosis and especially a manifestation with pachymeningitis is a notable rarity. CASE REPORT: A 26-year-old patient presented to the emergency department with acute onset, recurrent episodes of occipital headaches spreading over the whole cranium and vomiting without food consumption, for three days. The clinical examination did not reveal any neurological deficits. The laboratory exams showed no pathological findings. A CT examination with angiography did not detect any acute intracranial or vessel pathology. A lumbar puncture was performed to rule out subarachnoid hemorrhage. The results showed a lymphocytic pleocytosis of 400/µL, elevated protein levels of 1077 mg/dL and reduced glucose levels (CSF: 55 mg/dL, Serum: 118 mg/dL). Extensive infectiological examinations did not reveal any signs of infection, including Borrelia spp. and M. tuberculosis. No positive auto-antibodies or vasculitis-related auto-antibodies were detected. The CSF analysis showed negative oligoclonal bands but an isolated increase in ß2-microglobulin, neopterin, and IL-2R levels. The MRI examination revealed a dural gadolinium-enhancement, pronounced in the basal cerebral structures and the upper segment of the cervical spine, consistent with neurosarcoidosis. Corticosteroid treatment rapidly led to a significant improvement of the symptoms. No systemic manifestations of sarcoidosis were found. CONCLUSIONS: This case report aims to highlight aseptic meningitis with atypical, acute onset headache attacks as a possible manifestation of isolated neurosarcoidosis. Neurosarcoidosis is a clinical entity that requires prompt treatment to avoid permanent neurological deficits.