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Minerva Pediatrics Oct 2022Fever is an abnormal increase in body temperature that occurs as part of a specific biologic response mediated and controlled by the central nervous system. Despite the... (Review)
Review
Fever is an abnormal increase in body temperature that occurs as part of a specific biologic response mediated and controlled by the central nervous system. Despite the fact that most fevers are viral in origin, approaching a febrile child is always a concern for any physician. There is still a significant gap between current practice and scientific evidence. According to research, we are at a crossroad, with strong research evidence accumulating over the last few decades supporting a positive role for fever and the ongoing pressures of current practice to lower body temperature. Despite the fact that most pediatricians agree that treating a febrile child with antipyretics is primarily for the relief of fever symptoms, many continue to prescribe antipyretics for any child with fever, ignoring important research messages. By prescribing antipyretics to children who are only mildly febrile, pediatricians may contribute to fever phobia. We give parents the impression that fever is harmful and that antipyresis is beneficial when we focus on treating the fever. The purpose of this review is to present the evidence that is currently available regarding the management of the febrile child.
Topics: Child; Humans; Antipyretics; Fever; Body Temperature; Pediatricians; Parents
PubMed: 35822579
DOI: 10.23736/S2724-5276.22.06680-0 -
Annals of Internal Medicine Nov 2021Seasonal influenza epidemics of variable severity pose challenges to public health. Annual vaccination is the primary way to prevent influenza, and a wide range of...
Seasonal influenza epidemics of variable severity pose challenges to public health. Annual vaccination is the primary way to prevent influenza, and a wide range of vaccines are available, including inactivated or live attenuated standard-dose, recombinant vaccines, as well as adjuvanted or high-dose vaccines for persons aged 65 years or older. Persons at increased risk for influenza complications include young children, persons with underlying medical conditions, and older adults. Prompt diagnosis of influenza can facilitate early initiation of antiviral treatment that provides the greatest clinical benefit. This article summarizes recommendations for providers on influenza vaccination, diagnostic testing, and antiviral treatment.
Topics: Anaphylaxis; Antipyretics; Antiviral Agents; Chemoprevention; Coinfection; Fluid Therapy; Hospitalization; Humans; Infection Control; Influenza Vaccines; Influenza, Human; Referral and Consultation; Risk Assessment; Seasons; Vaccine Efficacy
PubMed: 34748378
DOI: 10.7326/AITC202111160 -
American Journal of Obstetrics and... Dec 2020This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an... (Review)
Review
This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an evidence-based contemporary approach for the management of this condition. Most trials that assessed the use of antibiotics in clinical chorioamnionitis included patients with a gestational age of ≥34 weeks and in labor. The first-line antimicrobial regimen for the treatment of clinical chorioamnionitis is ampicillin combined with gentamicin, which should be initiated during the intrapartum period. In the event of a cesarean delivery, patients should receive clindamycin at the time of umbilical cord clamping. The administration of additional antibiotic therapy does not appear to be necessary after vaginal or cesarean delivery. However, if postdelivery antibiotics are prescribed, there is support for the administration of an additional dose. Patients can receive antipyretic agents, mainly acetaminophen, even though there is no clear evidence of their benefits. Current evidence suggests that the administration of antenatal corticosteroids for fetal lung maturation and of magnesium sulfate for fetal neuroprotection to patients with clinical chorioamnionitis between 24 0/7 and 33 6/7 weeks of gestation, and possibly between 23 0/7 and 23 6/7 weeks of gestation, has an overall beneficial effect on the infant. However, delivery should not be delayed to complete the full course of corticosteroids and magnesium sulfate. Once the diagnosis of clinical chorioamnionitis has been established, delivery should be considered, regardless of the gestational age. Vaginal delivery is the safer option and cesarean delivery should be reserved for standard obstetrical indications. The time interval between the diagnosis of clinical chorioamnionitis and delivery is not related to most adverse maternal and neonatal outcomes. Patients may require a higher dose of oxytocin to achieve adequate uterine activity or greater uterine activity to effect a given change in cervical dilation. The benefit of using continuous electronic fetal heart rate monitoring in these patients is unclear. We identified the following promising interventions for the management of clinical chorioamnionitis: (1) an antibiotic regimen including ceftriaxone, clarithromycin, and metronidazole that provides coverage against the most commonly identified microorganisms in patients with clinical chorioamnionitis; (2) vaginal cleansing with antiseptic solutions before cesarean delivery with the aim of decreasing the risk of endometritis and, possibly, postoperative wound infection; and (3) antenatal administration of N-acetylcysteine, an antioxidant and antiinflammatory agent, to reduce neonatal morbidity and mortality. Well-powered randomized controlled trials are needed to assess these interventions in patients with clinical chorioamnionitis.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antioxidants; Antipyretics; Ceftriaxone; Cesarean Section; Chorioamnionitis; Clarithromycin; Clindamycin; Delivery, Obstetric; Endometritis; Evidence-Based Medicine; Female; Gentamicins; Gestational Age; Humans; Magnesium Sulfate; Metronidazole; Practice Guidelines as Topic; Pregnancy; Puerperal Infection; Tocolytic Agents
PubMed: 33007269
DOI: 10.1016/j.ajog.2020.09.044 -
Emergency Medicine Clinics of North... Aug 2021Pediatric fever is a common complaint in children. The most common cause is self-limited viral infection. However, neonates and young infants are evaluated and treated... (Review)
Review
Pediatric fever is a common complaint in children. The most common cause is self-limited viral infection. However, neonates and young infants are evaluated and treated differently than older, vaccinated, and clinically evaluable children. Neonates should be admitted to the hospital, young infants in the second month of life may be risk stratified, and those deemed low risk on testing may be sent home with close follow-up. Children older than 2 months may be evaluated clinically for signs of bacterial infection that require intervention. Urinary tract infections cause more than 90% of serious bacterial illness in children, and younger children have a higher incidence of infection.
Topics: Algorithms; Anemia, Sickle Cell; Anti-Bacterial Agents; Antipyretics; Biomarkers; C-Reactive Protein; Child; Fever; Humans; Incidence; Infant, Premature, Diseases; Infections; Neutropenia; Pediatric Emergency Medicine; Procalcitonin; Risk Assessment
PubMed: 34215406
DOI: 10.1016/j.emc.2021.04.011 -
JAMA Network Open Oct 2020Acetaminophen (paracetamol) and ibuprofen are the most widely prescribed and available over-the-counter medications for management of fever and pain in children. Despite... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Acetaminophen (paracetamol) and ibuprofen are the most widely prescribed and available over-the-counter medications for management of fever and pain in children. Despite the common use of these medications, treatment recommendations for young children remain divergent.
OBJECTIVE
To compare acetaminophen with ibuprofen for the short-term treatment of fever or pain in children younger than 2 years.
DATA SOURCES
Systematic search of the databases MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials and the trial registers ClinicalTrials.gov and the Australian New Zealand Clinical Trials Registry from inception to March 2019, with no language limits.
STUDY SELECTION
Studies of any design that included children younger than 2 years and directly compared acetaminophen with ibuprofen, reporting antipyretic, analgesic, and/or safety outcomes were considered. There were no limits on length of follow-up.
DATA EXTRACTION AND SYNTHESIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline, 2 authors independently extracted data and assessed quality. Data were pooled using a fixed-effects method if I2 was less than 50% and using a random-effects method if I2 was 50% or greater.
MAIN OUTCOMES AND MEASURES
The primary outcomes were fever or pain within 4 hours of treatment onset. Safety outcomes included serious adverse events, kidney impairment, gastrointestinal bleeding, hepatotoxicity, severe soft tissue infection, empyema, and asthma and/or wheeze.
RESULTS
Overall, 19 studies (11 randomized; 8 nonrandomized) of 241 138 participants from 7 countries and various health care settings (hospital-based and community-based) were included. Compared with acetaminophen, ibuprofen resulted in reduced temperature at less than 4 hours (4 studies with 435 participants; standardized mean difference [SMD], 0.38; 95% CI, 0.08-0.67; P = .01; I2 = 49%; moderate quality evidence) and at 4 to 24 hours (5 studies with 879 participants; SMD, 0.24; 95% CI, 0.03-0.45; P = .03; I2 = 57%; moderate-quality evidence) and less pain at 4 to 24 hours (2 studies with 535 participants; SMD, 0.20; 95% CI, 0.03-0.37; P = .02; I2 = 25%; moderate-quality evidence). Adverse events were uncommon. Acetaminophen and ibuprofen appeared to have similar serious adverse event profiles (7 studies with 27 932 participants; ibuprofen vs aceteminophen: odds ratio, 1.08; 95% CI, 0.87-1.33; P = .50, I2 = 0%; moderate-quality evidence).
CONCLUSIONS AND RELEVANCE
In this study, use of ibuprofen vs acetaminophen for the treatment of fever or pain in children younger than 2 years was associated with reduced temperature and less pain within the first 24 hours of treatment, with equivalent safety.
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Child, Preschool; Female; Fever; Humans; Ibuprofen; Infant; Male; Pain
PubMed: 33125495
DOI: 10.1001/jamanetworkopen.2020.22398 -
Journal of Clinical Pharmacology Nov 2019Metamizole, also known as dipyrone, was introduced to the market nearly a century ago. Due to its excellent analgesic, antipyretic, and spasmolytic properties combined... (Review)
Review
Metamizole, also known as dipyrone, was introduced to the market nearly a century ago. Due to its excellent analgesic, antipyretic, and spasmolytic properties combined with its mostly favorable gastrointestinal tolerability, the drug was extensively applied worldwide during the first decades after its market introduction. Although rare, agranulocytosis is a well-known adverse event of metamizole and led to its withdrawal from the market in a number of countries beginning in the 1960s. Nevertheless, metamizole is still a frequently used drug worldwide either legally (by prescription in some countries, over the counter in other countries) or without official approval (especially by immigrants knowing the drug from their home countries) or even illegally (due to its growing application as an adulterant in illicit drugs). Metamizole undergoes extensive metabolism in the liver and cases of potential metamizole-associated hepatotoxicity have been described. Here, the literature is extensively reviewed for the first time regarding hepatic effects associated with the use of metamizole.
Topics: Agranulocytosis; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Antipyretics; Dipyrone; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Nonprescription Drugs
PubMed: 31433499
DOI: 10.1002/jcph.1512 -
Journal of Zhejiang University.... Apr 2022Acetaminophen, also known as -acetyl--aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as... (Review)
Review
Acetaminophen, also known as -acetyl--aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as acetaminophen-induced liver injury (AILI). However, therapeutic doses of APAP can also induce AILI in patients with excessive alcohol intake or who are fasting. Hence, there is a need to understand the potential pathological mechanisms underlying AILI. In this review, we summarize three main mechanisms involved in the pathogenesis of AILI: hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. The relevant factors are elucidated and discussed. For instance, -acetyl--benzoquinone imine (NAPQI) protein adducts trigger mitochondrial oxidative/nitrosative stress during hepatocyte necrosis, danger-associated molecular patterns (DAMPs) are released to elicit sterile inflammation, and certain growth factors contribute to liver regeneration. Finally, we describe the current potential treatment options for AILI patients and promising novel strategies available to researchers and pharmacists. This review provides a clearer understanding of AILI-related mechanisms to guide drug screening and selection for the clinical treatment of AILI patients in the future.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Humans; Inflammation; Liver; Mice; Mice, Inbred C57BL; Necrosis
PubMed: 35403383
DOI: 10.1631/jzus.B2100977 -
Current Medical Research and Opinion Aug 2021A narrative review of randomized, blinded, controlled studies assessing the antipyretic effect of ibuprofen versus acetaminophen or combined or alternating treatment in... (Review)
Review
OBJECTIVE
A narrative review of randomized, blinded, controlled studies assessing the antipyretic effect of ibuprofen versus acetaminophen or combined or alternating treatment in children was conducted.
METHODS
Searches of the PubMed and Embase literature databases were conducted to identify relevant articles. Selected articles were limited to studies published in English that investigated OTC oral tablet and syrup formulations of acetaminophen and ibuprofen; there were no publication date limits. Open-label studies, nonrandomized studies, and those evaluating intravenous or suppository formulations of acetaminophen or ibuprofen were excluded. Variations in designs, endpoints, methods, and patient populations precluded our ability to conduct a formal systematic review.
RESULTS
At physician-directed dosing (acetaminophen 15 mg/kg vs ibuprofen 10 mg/kg), no significant differences in antipyretic effects from 0‒6 h and between 0‒6, ‒12, ‒24, or ‒48 h, with single or multiple-doses, respectively, were observed. Tolerability profiles at physician dosing were similar. In 14 over-the-counter dose comparisons (acetaminophen, 10-15 mg/kg; ibuprofen, 2.5-10 mg/kg), antipyresis favored ibuprofen in 6, was similar between groups in 7, and favored acetaminophen (15 mg/kg vs ibuprofen 5 mg/kg) in 1 comparison. Both medications were well tolerated. Efficacy favored combination over individual components in 3 of 4 studies; alternating use results were mixed. All combination or alternating treatments were well tolerated.
CONCLUSIONS
Antipyretic effects of ibuprofen and acetaminophen are similar at physician-directed doses; ibuprofen may be modestly superior at over-the-counter doses.
Topics: Acetaminophen; Administration, Intravenous; Analgesics, Non-Narcotic; Antipyretics; Child; Fever; Humans; Ibuprofen
PubMed: 33966545
DOI: 10.1080/03007995.2021.1928617 -
European Journal of Pediatrics Apr 2021The efficacy of antipyretics for preventing febrile seizure recurrence has been reported by a recent study, and the results might overturn previous evidence. We... (Meta-Analysis)
Meta-Analysis Review
The efficacy of antipyretics for preventing febrile seizure recurrence has been reported by a recent study, and the results might overturn previous evidence. We systematically reviewed the efficacy of antipyretics in the prevention of febrile seizure recurrence in children focused on the timing of its administration. We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases for randomized and quasi-randomized trials and prospective non-randomized studies of aged up to 60 months, diagnosed with febrile seizure, who were treated with antipyretics. Data were extracted from eight studies. Only one study reported that antipyretics prevented the recurrence of febrile seizures within the same fever episode (9.1% in the acetaminophen group vs. 23.5% in the control group, p < 0.01). Four studies found no evidence for the efficacy of antipyretics in preventing febrile seizure recurrence in distant fever episodes (odds ratio, 0.92; 95% confidence interval, 0.57-1.48, for two randomized controlled studies).Conclusion: This review provides very limited support for the use of antipyretics in preventing febrile seizure recurrence within the same fever episode and no evidence for its use in distant fever episodes. New studies are required to evaluate this topic further and determine whether the effectiveness of antipyretics is based on intervention timing. What is Known: • Reviews of prophylactic drug management among febrile seizure children found that antipyretics had no significant benefits. • Recent data suggest that antipyretics are effective in preventing febrile seizures. What is New: • Weak evidence suggests a possible role in preventing febrile seizure recurrence within the same fever episode. • There is clearly no role for antipyretic prophylaxis in preventing febrile seizures during distant fever episodes.
Topics: Acetaminophen; Aged; Antipyretics; Child; Humans; Pharmaceutical Preparations; Prospective Studies; Recurrence; Seizures, Febrile
PubMed: 33125519
DOI: 10.1007/s00431-020-03845-8 -
Hepatology (Baltimore, Md.) Nov 2022Sam50, a key component of the sorting and assembly machinery (SAM) complex, is also involved in bridging mitochondrial outer-membrane and inner-membrane contacts....
BACKGROUND AND AIMS
Sam50, a key component of the sorting and assembly machinery (SAM) complex, is also involved in bridging mitochondrial outer-membrane and inner-membrane contacts. However, the physiological and pathological functions of Sam50 remain largely unknown.
APPROACH AND RESULTS
Here we show that Sam50 interacts with MICOS (mitochondrial contact site and cristae organizing system) and ATAD3 (ATPase family AAA domain-containing protein 3) to form the Sam50-MICOS-ATAD3-mtDNA axis, which maintains mtDNA stability. Loss of Sam50 causes mitochondrial DNA (mtDNA) aggregation. Furthermore, Sam50 cooperates with Mic60 to bind to cardiolipin, maintaining the integrity of mitochondrial membranes. Sam50 depletion leads to cardiolipin externalization, which causes mitochondrial outer-membrane and inner-membrane (including crista membrane) remodeling, triggering Bax mitochondrial recruitment, mtDNA aggregation, and release. Physiologically, acetaminophen (an effective antipyretic and analgesic)-caused Sam50 reduction or Sam50 liver-specific knockout induces mtDNA release, leading to activation of the cGAS-STING pathway and liver inflammation in mice. Moreover, exogenous expression of Sam50 remarkably attenuates APAP-induced liver hepatoxicity.
CONCLUSIONS
Our findings uncover the critical role of Sam50 in maintaining mitochondrial membrane integrity and mtDNA stability in hepatocytes and reveal that Sam50 depletion-induced cardiolipin externalization is a signal of mtDNA release and controls mtDNA-dependent innate immunity.
Topics: Animals; Humans; Mice; Acetaminophen; Adenosine Triphosphatases; Antipyretics; bcl-2-Associated X Protein; Cardiolipins; DNA, Mitochondrial; HeLa Cells; Hepatocytes; Liver; Membrane Proteins; Mitochondrial Membranes; Mitochondrial Precursor Protein Import Complex Proteins; Mitochondrial Proteins; Nucleotidyltransferases
PubMed: 35313046
DOI: 10.1002/hep.32471