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1.
Sci Rep ; 14(1): 17858, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090409

RESUMEN

The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.


Asunto(s)
Colangitis , Drenaje , Fiebre , Humanos , Colangitis/tratamiento farmacológico , Masculino , Femenino , Fiebre/tratamiento farmacológico , Fiebre/etiología , Anciano , Estudios Retrospectivos , Enfermedad Aguda , Persona de Mediana Edad , Resultado del Tratamiento , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Antiinfecciosos/administración & dosificación , Recurrencia
3.
Sci Rep ; 14(1): 16431, 2024 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014068

RESUMEN

In malaria-endemic areas of Sub-Saharan Africa, overlap of clinical symptoms between malarial and non-malarial febrile illnesses can lead to empiric use of antibiotics among children. Our study aimed to illustrate the potential impact of decreasing malaria prevalence from malaria control efforts on antibiotic use. We constructed a probabilistic decision tree model representing antibiotic prescription in febrile children < 5 years. This model was used to predict change in absolute antibiotic use compared to baseline under levels of decreasing malaria prevalence. Model parameters were based on data from a hospital study in Ghana and validated via literature review. The baseline prevalence of malaria diagnoses was 52% among all hospitalized children. For our main results, we reported outcomes for a scenario representing a 50% decrease in malaria prevalence. Compared to baseline, absolute antibiotic prescription decreased from a baseline of 639 doses (95% CI 574-694) to 575 (95% CI 502-638). This reflected a 10% (95% CI 7%-13%) decrease in absolute antibiotic use. Our findings demonstrate that effective malaria control can reduce pediatric antibiotic use. However, until substantial progress is made in developing accurate diagnostics for non-malarial febrile illnesses, further reductions in antibiotic use will remain a challenge.


Asunto(s)
Antibacterianos , Malaria , Humanos , Malaria/tratamiento farmacológico , Malaria/epidemiología , Antibacterianos/uso terapéutico , Prevalencia , Preescolar , Lactante , Ghana/epidemiología , Femenino , Masculino , Fiebre/tratamiento farmacológico , Fiebre/epidemiología , Niño
4.
Am J Emerg Med ; 83: 69-75, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38976929

RESUMEN

OBJECTIVES: To determine whether there is a difference in antibiotic administration time and prognosis in afebrile sepsis patients compared to febrile sepsis patients. METHODS: This was retrospective multicenter observational study. Data collected from three referral hospitals. Data were collected from May 2014 through February 2016 under the SEPSIS-2 criteria and from March 2016 to April 2020 under the newly released SEPSIS-3 criteria. Patients were divided into two groups based on body temperature: afebrile (<37.3 °C) and febrile (≥37.3 °C). The relationship between initial body temperature and 28-day mortality were analyzed using multivariable logistic regression. The subgroup analysis was conducted on patients with complete Hour-1 bundle performance records. RESULTS: We included 4293 patients in this study. Initial body temperatures in 28-day survivors were significantly higher than in 28-day non-survivors (37.5 °C ± 1.2 °C versus 37.1 °C ± 1.2 °C, p < 0.01). Multivariable logistic regression analysis was performed in afebrile and febrile sepsis patients. Adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.76 (95% Confidence interval 1.46-2.12). As a result of performing the Hour-1 bundle, the number of patients who received antibiotics within 1 h was smaller in the afebrile sepsis patients (323/2076, 15.6%) than in the febrile sepsis patients (395/2156, 18.3%) (p = 0.02). In the subgroup analysis of patients with complete Hour-1 bundle performance records adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.68 (95% Confidence interval 1.34-2.11). The febrile sepsis patients received antibiotics faster than the afebrile sepsis patients (175.5 ± 207.9 versus 209.3 ± 277.9, p < 0.01). CONCLUSIONS: Afebrile sepsis patients were associated with higher 28-day mortality compared to their febrile counterparts and were delayed in receiving antibiotics. This underscores the need for improved early detection and treatment strategies for the afebrile sepsis patients.


Asunto(s)
Antibacterianos , Visitas a la Sala de Emergencias , Servicio de Urgencia en Hospital , Fiebre , Sepsis , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Temperatura Corporal , Visitas a la Sala de Emergencias/estadística & datos numéricos , Fiebre/tratamiento farmacológico , Mortalidad Hospitalaria , Modelos Logísticos , Pronóstico , Estudios Retrospectivos , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Tiempo de Tratamiento/estadística & datos numéricos
6.
Antiviral Res ; 228: 105938, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38897317

RESUMEN

We compared the duration of fever in children infected with A(H1N1)pdm09, A(H3N2), or influenza B viruses following treatment with baloxavir marboxil (baloxavir) or neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, or laninamivir). This observational study was conducted at 10 outpatient clinics across 9 prefectures in Japan during the 2012-2013 and 2019-2020 influenza seasons. Patients with influenza rapid antigen test positive were treated with one of four anti-influenza drugs. The type/subtype of influenza viruses were identified from MDCK or MDCK SIAT1 cell-grown samples using two-step real-time PCR. Daily self-reported body temperature after treatment were used to evaluate the duration of fever by treatment group and various underlying factors. Among 1742 patients <19 years old analyzed, 452 (26.0%) were A(H1N1)pdm09, 827 (48.0%) A(H3N2), and 463 (26.0%) influenza B virus infections. Among fours treatment groups, baloxavir showed a shorter median duration of fever compared to oseltamivir in univariate analysis for A(H1N1)pdm09 virus infections (baloxavir, 22.0 h versus oseltamivir, 26.7 h, P < 0.05; laninamivir, 25.5 h, and zanamivir, 25.0 h). However, this difference was not significant in multivariable analyses. For A(H3N2) virus infections, there were no statistically significant differences observed (20.3, 21.0, 22.0, and 19.0 h) uni- and multivariable analyses. For influenza B, baloxavir shortened the fever duration by approximately 15 h than NAIs (20.3, 35.0, 34.3, and 34.1 h), as supported by uni- and multivariable analyses. Baloxavir seems to have comparable clinical effectiveness with NAIs on influenza A but can be more effective for treating pediatric influenza B virus infections than NAIs.


Asunto(s)
Antivirales , Dibenzotiepinas , Fiebre , Guanidinas , Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Virus de la Influenza B , Gripe Humana , Morfolinas , Oseltamivir , Piranos , Piridonas , Ácidos Siálicos , Triazinas , Zanamivir , Humanos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Antivirales/uso terapéutico , Antivirales/farmacología , Virus de la Influenza B/efectos de los fármacos , Virus de la Influenza B/genética , Niño , Zanamivir/uso terapéutico , Zanamivir/análogos & derivados , Zanamivir/farmacología , Triazinas/uso terapéutico , Triazinas/farmacología , Guanidinas/uso terapéutico , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Piridonas/uso terapéutico , Dibenzotiepinas/uso terapéutico , Japón , Femenino , Masculino , Preescolar , Oseltamivir/uso terapéutico , Fiebre/tratamiento farmacológico , Fiebre/virología , Adolescente , Morfolinas/uso terapéutico , Lactante , Estaciones del Año , Tiepinas/uso terapéutico , Tiepinas/farmacología , Oxazinas/uso terapéutico , Factores de Tiempo , Benzoxazinas/uso terapéutico
7.
Trop Med Int Health ; 29(8): 706-714, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38888511

RESUMEN

OBJECTIVE: Many children in sub-Saharan Africa die from infectious diseases like malaria, pneumonia, and diarrhoea that can be prevented by early diagnosis, effective and targeted treatment. This study aimed to gain insights into case management practices by parents before they present their children to hospital. METHODS: We conducted a cross-sectional study among 332 parents attending a district hospital with their under-fives symptomatic with fever and/or diarrhoea between November 2019 and July 2020 in rural Tanzania. Timely and targeted treatment was defined as seeking health care within 24 h of fever onset, and continued fluid intake in case of diarrhoea. RESULTS: The main admission diagnoses were acute respiratory infections (61.8%), malaria (25.3%), diarrhoea (18.4%) and suspected sepsis (8.1%). The majority of children (91%) received treatment prior to admission, mostly antipyretics (75.6%), local herbal medicines (26.8%), and antibiotics (17.8%)-half of them without prescription from a clinician. For diarrhoea, the use of oral rehydration solution was rare (9.0%), although perceived as easily accessible and affordable. 49.4% of the parents presented their children directly to the hospital, 23.2% went to a pharmacy/drug shop and 19.3% to a primary health facility first. Malaria symptoms began mostly 3 days before the hospital visit; only 25.4% of febrile children visited any health facility within 24 h of disease onset. Prior use of local herbal medicine (AOR = 3.2; 95% CI 1.4-7.3), visiting the pharmacy (adjusted Odds Ratio [AOR] = 3.1; 95% confidence interval [CI]: 1.0-9.8), the dispensary being the nearest health facility (AOR = 3.0; 95% CI: 1.5-6.2), and financial difficulties (AOR = 2.2; 95% CI 1.1-4.5) were associated with delayed treatment. CONCLUSION: This study suggests that antipyretics and antibiotics dispensed at pharmacies/drug shops, as well as use of local herbal medicines, delay early diagnosis and treatment, which can be life-threatening. Pharmacies/drug shops could be integrated as key focal points for sensitising community members on how to respond to paediatric illnesses and encourage the use of oral rehydration solutions.


Asunto(s)
Diarrea , Fiebre , Población Rural , Humanos , Tanzanía/epidemiología , Estudios Transversales , Fiebre/tratamiento farmacológico , Fiebre/terapia , Preescolar , Diarrea/terapia , Diarrea/tratamiento farmacológico , Femenino , Masculino , Lactante , Padres , Malaria/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico
8.
JAMA Neurol ; 81(8): 857-865, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38857015

RESUMEN

Importance: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae. Objective: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher. Design, Setting, and Participants: This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023. Intervention: The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher. Main Outcomes and Measures: The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance. Results: Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07). Conclusions and Relevance: This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia. Trial Registration: ClinicalTrials.gov Identifier: NCT03399318.


Asunto(s)
Acetaminofén , Antipiréticos , Ibuprofeno , Humanos , Ibuprofeno/uso terapéutico , Acetaminofén/uso terapéutico , Femenino , Masculino , Preescolar , Antipiréticos/uso terapéutico , Niño , Malaui , Malaria Cerebral/tratamiento farmacológico , Malaria Cerebral/complicaciones , Fiebre/tratamiento farmacológico , Quimioterapia Combinada , Zambia
9.
Acta Paediatr ; 113(8): 1927-1933, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38747530

RESUMEN

AIM: To investigate the rate of dispensed antibiotic prescriptions to children and adolescents with PFAPA and compare this with the rate for children in the general population. Furthermore, to compare dispensed antibiotic prescription rates before and after a diagnosis of PFAPA was established. METHODS: Patients aged 0-17 years and diagnosed with PFAPA between 1 January 2006 to 31 October 2017 were included retrospectively. Data on dispensed drug prescriptions were obtained from the Swedish National Prescribed Drug Register. RESULTS: The PFAPA cohort received more antibiotic prescriptions than the general population in all but one of the age groups and time periods that were analysed. The largest difference was seen in 2014-2017 in the youngest age group (0-4 years) when children with PFAPA received 1218 antibiotic prescriptions per 1000 person years compared to 345 in the general population (IRR 3.5; 95% CI 2.8-4.4). The yearly number of antibiotic prescriptions to PFAPA patients was reduced from 2.1 before diagnosis to 0.8 after diagnosis, a reduction of 62%. CONCLUSION: This study shows higher rates of dispensed antibiotic prescriptions for children with PFAPA than in the general population. The reduction of prescriptions after an established PFAPA diagnosis indicates that antibiotics were previously incorrectly prescribed for PFAPA episodes.


Asunto(s)
Antibacterianos , Fiebre , Linfadenitis , Faringitis , Estomatitis Aftosa , Humanos , Antibacterianos/uso terapéutico , Niño , Linfadenitis/tratamiento farmacológico , Preescolar , Lactante , Faringitis/tratamiento farmacológico , Estomatitis Aftosa/tratamiento farmacológico , Estomatitis Aftosa/diagnóstico , Adolescente , Estudios Retrospectivos , Masculino , Femenino , Fiebre/tratamiento farmacológico , Prescripciones de Medicamentos/estadística & datos numéricos , Suecia , Recién Nacido , Cuello , Pautas de la Práctica en Medicina/estadística & datos numéricos
10.
Sci Rep ; 14(1): 10897, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740876

RESUMEN

Urinary tract infection (UTI) is the most prevalent urological condition worldwide. Choosing appropriate antibiotics for patients who have fever before receiving a culture result is challenging. This retrospective study enrolled patients 394 patients hospitalized at Gangneung Asan Hospital for UTI from May 2017 to April 2021. Fever at 48 h of hospitalization was the analysis point, as this is when the response to antibiotic therapy manifest, although the results of antibiogram are not available. Multivariate analysis was performed to assess the correlation between ESBL producing bacteria (EPB) and fever at 48 h. Overall, 36.3% of patients had EPB and 27.9% had fever at 48 h. In multivariate analysis, a significant positive association was found between EPB and fever (odds ratio 1.17, 95% CI 1.05-1.30, P = 0.004) Female had negative association with multivariate model (OR 0.83, 95% CI 0.73-0.94, P = 0.004). Diabetes did not demonstrate a significant association with EPB. (OR 1.10, 95% CI 0.99-1.22, P = 0.072). Fever at 48 h is associated with EPB and could be considered a predictive factor for EPB infection in patients with UTI. Antibiotic escalation may be considered in patients with fever at 48 h.


Asunto(s)
Antibacterianos , Fiebre , Infecciones Urinarias , beta-Lactamasas , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/tratamiento farmacológico , Femenino , Masculino , beta-Lactamasas/metabolismo , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Fiebre/microbiología , Fiebre/tratamiento farmacológico , Anciano de 80 o más Años , Adulto
11.
J Ethnopharmacol ; 331: 118288, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38705426

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Xiaoer-Feire-Qing granules (XEFRQ) has been used to treat pyretic pulmonary syndrome (PPS) in children for many years. The function of the lungs is considered to be closely related to the large intestine in TCM. PURPOSE: We aimed to investigate the effects of XEFRQ on PPS and the underlying mechanisms via network pharmacology and animal experiments. METHODS: The TCMSP platform was used to identify the ingredients and potential targets of XEFRQ. The GeneCards, OMIM, and TTD databases were used to predict PPS-associated targets. Cytoscape 3.9.1 was employed to construct the protein-protein interaction network, and target prediction was performed by GO and KEGG analyses. For the animal experiment, a PPS model was constructed by three cycles of nasal drip of Streptococcus pneumoniae (STP; 0.5 mL/kg). The animals were randomly divided into the following four groups according to their weight (n = 10 rats per group): the blank group, the model group, the XEFRQ-L (16.3 g/kg) group, and the XEFRQ-H (56.6 g/kg) group. Rats in the blank group and the model group were given 0.5% CMC-Na by gavage. The general conditions of the rats were observed, and their food-intake, body weight, and body temperature were recorded for 14 days. After the intervention of 14 days, serum was collected to detect inflammatory cytokines (TNF-α, IL-1ß, and PGE2) and neurotransmitters (5-HT, SP, and VIP). H&E staining was used to observe the pathological morphology of lung and colon tissue. AQP3 expression was detected by Western blot. In addition, the gut microbiota in cecal content samples were analyzed by 16S rDNA high-throughput sequencing. RESULTS: Our network analysis revealed that XEFRQ may alleviate PPS injury by affecting the levels of inflammatory cytokines and neurotransmitters and mitigating STP-induced PPS.In vivo validation experiments revealed that XEFRQ improved STP-induced PPS and reduced the expression of inflammatory cytokines and neurotransmitters. Notably, XEFRQ significantly decreased the protein expression levels of AQP3, which was associated with dry stool. Our gut microbiota analysis revealed that the relative abundance of [Eubacterium]_ruminantium_group, Colidextribacter, Romboutsia, and Oscillibacter was decreased, which means XEFRQ exerts therapeutic effects against PPS associated with these bacteria. CONCLUSION: Our results demonstrate that XEFRQ alleviates PPS by affecting the lungs and intestines, further guiding its clinical application.


Asunto(s)
Medicamentos Herbarios Chinos , Pulmón , Farmacología en Red , Ratas Sprague-Dawley , Streptococcus pneumoniae , Animales , Medicamentos Herbarios Chinos/farmacología , Pulmón/efectos de los fármacos , Pulmón/microbiología , Pulmón/patología , Pulmón/metabolismo , Masculino , Streptococcus pneumoniae/efectos de los fármacos , Ratas , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mapas de Interacción de Proteínas , Intestinos/efectos de los fármacos , Intestinos/microbiología , Fiebre/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/microbiología
12.
J Ethnopharmacol ; 331: 118283, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38734393

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Syagrus coronata, a palm tree found in northeastern Brazil, popularly known as licuri, has socioeconomic importance for the production of vegetable oil rich in fatty acids with nutritional and pharmacological effects. Licuri oil is used in traditional medicine to treat inflammation, wound healing, mycosis, back discomfort, eye irritation, and other conditions. AIM OF THE STUDY: The study aimed to evaluate the antinociceptive, anti-inflammatory, and antipyretic effects of treatment with Syagrus coronata fixed oil (ScFO), as well as to determine the safety of use in mice. MATERIALS AND METHODS: Initially, the chemical characterization was performed by gas chromatography-mass spectrometry. Acute single-dose oral toxicity was evaluated in mice at a dose of 2000 mg/kg. Antinociceptive activity was evaluated through abdominal writhing, formalin, and tail dipping tests, and the anti-inflammatory potential was evaluated through the model of acute inflammation of ear edema, peritonitis, and fever at concentrations of 25, 50, and 100 mg/kg from ScFO. RESULTS: In the chemical analysis of ScFO, lauric (43.64%), caprylic (11.7%), and capric (7.2%) acids were detected as major. No mortality or behavioral abnormalities in the mice were evidenced over the 14 days of observation in the acute toxicity test. ScFO treatment decreased abdominal writhing by 27.07, 28.23, and 51.78% at 25, 50, and 100 mg/kg. ScFO demonstrated central and peripheral action in the formalin test, possibly via opioidergic and muscarinic systems. In the tail dipping test, ScFO showed action from the first hour after treatment at all concentrations. ScFO (100 mg/kg) reduced ear edema by 63.76% and leukocyte and neutrophil migration and IL-1ß and TNF-α production in the peritonitis test. CONCLUSION: Mice treated with ScFO had a reduction in fever after 60 min at all concentrations regardless of dose. Therefore, the fixed oil of S. coronata has the potential for the development of new pharmaceutical formulations for the treatment of pain, inflammation, and fever.


Asunto(s)
Analgésicos , Antiinflamatorios , Edema , Aceites de Plantas , Animales , Analgésicos/farmacología , Analgésicos/aislamiento & purificación , Analgésicos/toxicidad , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Aceites de Plantas/farmacología , Masculino , Edema/tratamiento farmacológico , Edema/inducido químicamente , Dolor/tratamiento farmacológico , Peritonitis/tratamiento farmacológico , Antipiréticos/farmacología , Arecaceae/química , Femenino , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Fiebre/tratamiento farmacológico , Fiebre/inducido químicamente , Administración Oral , Modelos Animales de Enfermedad
13.
Immunobiology ; 229(3): 152812, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38781756

RESUMEN

Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.


Asunto(s)
Antiinflamatorios , Inosina , Lipopolisacáridos , Inosina/farmacología , Animales , Ratones , Antiinflamatorios/farmacología , Antipiréticos/farmacología , Masculino , Inflamación/tratamiento farmacológico , Fiebre/tratamiento farmacológico , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Citocinas/metabolismo , Medicamentos Herbarios Chinos/farmacología
14.
J Pharm Biomed Anal ; 246: 116219, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38759325

RESUMEN

Qingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1ß, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever.


Asunto(s)
Antipiréticos , Medicamentos Herbarios Chinos , Fiebre , Metabolómica , Animales , Conejos , Antipiréticos/farmacología , Medicamentos Herbarios Chinos/farmacología , Metabolómica/métodos , Fiebre/tratamiento farmacológico , Masculino , Modelos Animales de Enfermedad , Lipopolisacáridos/farmacología , Cromatografía Líquida de Alta Presión/métodos
15.
Clin Microbiol Infect ; 30(8): 1029-1034, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38648896

RESUMEN

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.


Asunto(s)
Neoplasias , Infecciones del Sistema Respiratorio , Virosis , Humanos , Masculino , Femenino , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/virología , Niño , Preescolar , Estudios Prospectivos , Virosis/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Chile , Neutropenia Febril/tratamiento farmacológico , Lactante , Privación de Tratamiento , Fiebre/tratamiento farmacológico , Resultado del Tratamiento , Antiinfecciosos/uso terapéutico , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Hospitalización , Adolescente
16.
Malar J ; 23(1): 95, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582830

RESUMEN

BACKGROUND: The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania. METHODS: A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety. RESULTS: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.


Asunto(s)
Antimaláricos , Artemisininas , Malaria Falciparum , Malaria , Niño , Humanos , Antimaláricos/efectos adversos , Combinación Arteméter y Lumefantrina/efectos adversos , Tanzanía , Reinfección/inducido químicamente , Reinfección/tratamiento farmacológico , Artemisininas/efectos adversos , Arteméter/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/prevención & control , Amodiaquina/uso terapéutico , Malaria/tratamiento farmacológico , Fiebre/tratamiento farmacológico , Combinación de Medicamentos , Etanolaminas/efectos adversos , Plasmodium falciparum
17.
PLoS One ; 19(4): e0294823, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38640099

RESUMEN

BACKGROUND: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. METHODS: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. DISCUSSION: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.


Asunto(s)
Antipiréticos , Lesiones Encefálicas , Malaria , Humanos , Niño , Antipiréticos/uso terapéutico , Cuidados Posteriores , Alta del Paciente , Fiebre/complicaciones , Fiebre/tratamiento farmacológico , Fiebre/prevención & control , Imagen por Resonancia Magnética , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Observacionales como Asunto
18.
Artículo en Inglés | MEDLINE | ID: mdl-38688819

RESUMEN

INTRODUCTION: Acute respiratory infections (ARI) are a common cause of inappropriate antibiotic prescription (ATB) in pediatrics. FebriDx® is a rapid diagnostic test that differentiates between viral and bacterial infections. The objective is to analyse the impact of FebriDx® on ATB prescription when managing febrile ARI. METHODS: Prospective study carried out in patients aged 1-<18 years with febrile ARI in the emergency department. FebriDx® was performed and the impact on management was evaluated at follow-up. RESULTS: A total of 216 patients were included. Clinical assessment and FebriDx® result coincided coincided in 174 (80.5%) cases. A modification of the initial therapeutic plan was made in 22 (52.4%) of the 42 discordant ones (10.2% of the overall patients). In pneumonia the impact was 34.5%; in all cases it involved not prescribing ATB. CONCLUSIONS: FebriDx® could be a useful tool in the management of pediatric patients with febrile ARI to optimize ATB prescription.


Asunto(s)
Fiebre , Infecciones del Sistema Respiratorio , Humanos , Estudios Prospectivos , Preescolar , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/diagnóstico , Lactante , Niño , Masculino , Fiebre/tratamiento farmacológico , Fiebre/etiología , Femenino , Enfermedad Aguda , Adolescente , Antibacterianos/uso terapéutico
19.
BMC Public Health ; 24(1): 1089, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641808

RESUMEN

INTRODUCTION: Fever and cough in under-five children are common and predominately self-limiting illnesses. Inappropriate prescribing of antibiotics in sub-Saharan Africa is a significant public health concern. However, prescription sources and use among children with fever or cough have not been explored. Therefore, we explored the factors associated with the use of antibiotics obtained from prescription and non-prescription sources for children with illnesses associated with fever and cough. METHODS: A secondary data analysis was conducted based on the Demographic and Health Survey (DHS) data from 37 sub-Saharan African countries. A total weighted sample of 18,866 under-five children who had a fever/cough and took antibiotics were considered for this study. Given the hierarchical nature of DHS data and the use of antibiotics prescribed from the formal healthcare setting (> 10%), a multilevel modified poisson regression model was fitted. Deviance was used for model comparison and the model with the lowest deviance value was chosen as the best-fitted model. Variables with p ≤ 0.2 in the bivariable analysis were considered for the multivariable modified poisson regression model. In the multivariable multilevel modified poisson regression model, the Adjusted Prevalence Odds Ratio (APOR) with a 95% Confidence Interval (CI) and p-value < 0.05 were reported to declare a significant association with taking antibiotics for fever/cough prescribed from formal healthcare setting. RESULTS: In sub-Saharan Africa, the proportion of use of antibiotics from informal healthcare setting for fever and cough among under-five children was 67.19% (95% CI: 66.51%, 67.85%). In the multilevel modified poisson regression analysis; residing in a rural area (APOR = 1.08, 95% CI: 1.04, 1.12), a child aged 36-47 months (APOR = 0.94, 95% CI: 0.90, 0.98), a child aged 48-59 months (APOR = 0.89, 95% CI: 0.84, 0.94), maternal primary education (APOR = 0.96, 95% CI: 0.93, 0.99), maternal secondary education (APOR = 0.95, 95% CI: 0.92, 0.99), belonged the middle household wealth status (APOR = 1.07, 95% CI: 1.02, 1.11), maternal exposure to news/electronic media (APR = 1.06, 95% CI: 1.02, 1.10), being from a household with 2 under-five children (APR = 0.94, 95% CI: 0.91, 0.97), being from a household with 3 under-five children (APR = 0.89, 95% CI: 0.85, 0.93), being from a household with 4 under-five children (APR = 0.90, 95% CI: 0.83, 0.98), and children of caregivers who were not involved in decision-making for their child health issues were significantly associated with taking antibiotics prescribed from formal healthcare setting for fever/cough among under-five children. CONCLUSION: Only two-thirds of the antibiotics used for children under five who had fever and cough were prescribed from formal healthcare setting. Our findings underscore the significance of addressing healthcare disparities, improving access to qualified healthcare providers, promoting maternal education, and empowering mothers in healthcare decision-making to ensure appropriate antibiotic use in this vulnerable population. Further research and interventions targeted at these factors are warranted to optimize antibiotic prescribing practices and promote responsible antibiotic use in the management of fever and cough in under-five children.


Asunto(s)
Antibacterianos , Fiebre , Femenino , Humanos , Antibacterianos/uso terapéutico , Población Negra , Tos/tratamiento farmacológico , Estudios Transversales , Fiebre/tratamiento farmacológico , Fiebre/epidemiología , África del Sur del Sahara , Masculino , Recién Nacido , Lactante , Preescolar
20.
Infect Dis (Lond) ; 56(8): 644-652, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38647537

RESUMEN

BACKGROUND: Primary care physicians played an important role in the global response during the COVID-19 pandemic, but with the absence of laboratory and diagnostics services, the move to telehealth and the focus on respiratory assessment, they faced increased uncertainty when making clinical decisions. OBJECTIVES: This paper aims to examine the impact of the pandemic on decisions made by primary care physicians, as measured by referrals to chest X-ray and laboratory tests and by prescriptions of antibiotics. METHODS: We conducted a retrospective study of all visits recorded with fever or cough, presenting to 209 community clinics in Southern Israel during the years 2018-2022. We describe changes in outcome rates across time and use multivariate generalised linear mixed effects model to compare the odds of referrals and prescriptions between periods, while accounting for gender, age, clinic sector, visit type, diagnosis, and season. RESULTS: In total, 609,823 visits to primary care physicians complied with the cohort definitions. Social restrictions were associated with a decline in all measured outcomes for primary care physician decisions, most prominently among ages 20-59, for throat culture referral during the first lockdown (OR = 0.46) and for cephalosporine prescription during the second lockdown (OR = 0.55). This trend persisted following the cancellation of the restrictions. CONCLUSIONS: Despite higher uncertainty during the COVID-19 social restrictions, the overall course of clinical decision-making processes was maintained, and was associated with a reduction in the use of auxiliary resources, which can improve the quality of patient care by lowering costs and supporting prevention of future antibiotics resistance.


Asunto(s)
COVID-19 , Médicos de Atención Primaria , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Israel/epidemiología , Adulto Joven , Anciano , SARS-CoV-2 , Derivación y Consulta/estadística & datos numéricos , Toma de Decisiones Clínicas , Adolescente , Antibacterianos/uso terapéutico , Lactante , Preescolar , Niño , Tos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Fiebre/tratamiento farmacológico , Atención Primaria de Salud
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