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Background: Maternal fever during pregnancy has been associated with an increased risk of genital malformations, but the implication for long-term reproductive health in the offspring is unknown., Objectives: To investigate associations between timing, duration, and temperature of fetal exposure to maternal fever and sons' semen quality, testicular volume, and levels of reproductive hormones in early adulthood. Further, to examine whether concurrent use of antipyretics and/or antibiotics modified the effect., Materials and Methods: We used the Fetal Programming of Semen Quality cohort consisting of men born to women enrolled in the Danish National Birth Cohort. Self-reported information on maternal fever was collected twice during pregnancy (median 16 and 31 pregnancy weeks) and categorized as any fever during pregnancy, fever during early pregnancy (weeks 1-15), and fever exclusively during late pregnancy (weeks 16-42). Semen quality and concentrations of reproductive hormones were measured at a clinical examination at the age of 18.9 years. We used negative binomial regression to examine the associations, adjusting for maternal age at birth, maternal smoking, family occupational status, and precision variables related to semen quality and hormonal levels, for example, abstinence time., Results: 986 men were included in the study, of which 23% had mothers reporting at least one episode of fever. We found no strong indications of associations between maternal fever during pregnancy and male reproductive health in young men. Concurrent use of antipyretics and antibiotics did not modify the association., Discussion: Strengths include the large sample size, prospectively collected data, and the adjustment for maternal factors during pregnancy and important precision variables. A limitation is the crude self-reported information on maternal fever., Conclusion: We found no evidence to support that timing, duration, or temperature of maternal fever during pregnancy has a long-term impact on semen characteristics, testicular volume, or level of reproductive hormones in male offspring., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Understanding how pharmaceutical opioids and antipyretic analgesics interact with the immune system potentially has major clinical implications for management of patients with infectious diseases and surgical and critical care patients. An electronic search was carried out on MEDLINE, EMBASE, PsycINFO, CENTRAL and the Cochrane library to identify reports describing the immunomodulatory effects of opioid analgesics and antipyretic analgesics, and their effects in infectious diseases. In adaptive immunity, nonsteroidal anti-inflammatory drugs have divergent effects: augmenting cell-mediated immunity but inhibiting humoral immunity. Nonsteroidal anti-inflammatory drugs have demonstrated a beneficial role in Mycobacterium tuberculosis infection and histoplasmosis in animals, and may be plausible adjuvants to antimicrobial agents in these diseases. There is a need to evaluate these findings rigorously in human clinical trials. There is preliminary evidence demonstrating antiviral effects of indomethacin in SARS CoV-2 in vitro; however, uncertainty regarding its clinical benefit in humans needs to be resolved in large clinical trials. Certain opioid analgesics are associated with immunosuppressive effects, with a developing understanding that fentanyl, morphine, methadone and buprenorphine suppress innate immunity, whilst having diverse effects on adaptive immunity. Morphine suppresses key cells of the innate immunity and is associated with greater risk of infection in the postsurgical setting. Efforts are needed to achieve adequate analgesia whilst avoiding suppression of the innate immunity in the immediate postoperative period caused by certain opioids, particularly in cancer surgery., (© 2022 British Pharmacological Society.)

Diagnostic reasoning is the thought process used to arrive at a diagnosis based on symptoms, examination findings, and laboratory values. Diagnosis is categorized as nonanalytic reasoning (intuition) and analytic reasoning (analysis). Rehabilitation nutrition involves the diagnosis of nutritional disorders, sarcopenia, and excess or deficient nutrient intake. There is usually only one correct answer for the presence or absence of these. On the other hand, there may be no single correct answer for the causes of anorexia, weight loss, or sarcopenia, and analytical reasoning is required. In this case, diagnostic reasoning involves hypotheses. Simply using nutritional supplements without performing diagnostic reasoning about these causes is like prescribing antipyretic analgesics to a patient with a headache without diagnosing the cause of the headache. To maximize function and quality of life in rehabilitation nutrition, it is necessary to suspect the common causes of anorexia, weight loss, and sarcopenia in all cases. [ABSTRACT FROM AUTHOR]

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-1β, 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models., Aim of Study: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms., Materials and Methods: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining., Results: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway., Conclusion: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Tetrastigma hemsleyanum Diels et Gilg, is one of the perennial evergreen plants with grass vine, which has obvious curative effect on severe infectious diseases. Although Tetrastigma hemleyanum has long been recognized for its capacity of antipyretic and antitoxic, its specific mechanism is unknown., Aim of the Study: To evaluate the antipyretic effect of Tetrastigma hemleyanum polysaccharide (THP) on mice with dry yeast-induced fever, and to explore its specific antipyretic mechanism., Methods: In this study, THP was administered by aerosol in febrile mice. The rectal temperatures of treated animals were monitored at different time points. Histopathological evaluation and various inflammatory indexes were used to assess inflammatory damage. The concentration variations of the central neurotransmitter, endocrine system, substance and energy metabolism indicators were measured to explore the physiological mechanism. Quantitative real-time PCR, Western bolt and Immunohistochemistry were performed to identify the correlation between antipyretic and TLR4/NF-κB signaling pathway., Results: THP reduced the body temperature of febrile mice induced by dry yeast, as well as the levels of thermogenic cytokines and downregulated the contents of thermoregulatory mediators. THP alleviated the pathological damage of liver and hypothalamus caused by fever. In addition, THP decreased the secretion of thyroid hormone, substance and energy metabolism related indicators. Furthermore, THP significantly suppressed TLR4/NF-κB signaling pathway-related indicators., Conclusions: In conclusion, our results suggest that inhaled THP exerts antipyretic effect by mediating the thermoregulatory mediator, decreasing the content of pyrogenic factors to lower the body temperature, and eventually restoring the high metabolic level in the body to normal via inhibiting TLR4/NF-κB signaling pathway. The study provides a reasonable pharmacodynamic basis for the treatment of polysaccharide in febrile-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Cyperus iria L. is a sedge belongs to Cyperaceae family. Tuber of this plant is traditionally used in fever., Aim of the Study: This study aimed to verify the effectiveness of this plant part against fever. Additionally, antinociceptive effect of the plant was evaluated., Materials and Methods: Antipyretic effect was evaluated by yeast induced hyperthermia experiment. Antinociceptive effect was determined by acetic acid induced writhing test and hot plate test. Four different doses of plant extract were used in mice model., Results: Extract at dose of 400 mg/kg.bw produced greater effect than paracetamol; reduction of elevated mice body temperature was observed by 2.6 °F and 4.2 °F after 4 h by paracetamol and 400 mg/kg.bw extract respectively. In acetic acid writhing test, extract at 400 mg/kg.bw and diclofenac were found to have equivalent effects producing percentage inhibition of writhing of 67.68% and 68.29% respectively. In hot plat test, significant reduction in latency was also observed after administration of plant extracts. Mean percent maximal effect was 83.55% and 67.26% for ketorolac and extract (400 mg/kg.bw) respectively., Conclusion: Our study endorsed the traditional use of C. iria tuber in fever with possible antinociceptive effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The simultaneous monitoring of individual or multiple diseases can be achieved by selecting therapeutic medicines used to treat the primary symptoms of the condition as biomarkers in wastewater. This study proposes a novel approach to monitor the prevalence of COVID-19 and influenza A (H1N1) by selecting nine medicines to serve as biomarkers, including three antipyretics, three antivirals, and three cough suppressants. To verify our approach, wastewater samples were collected from seventeen urban and five rural wastewater treatment plants (WWTPs) in a Chinese city over a period of one year. The use of antipyretics increased notably during the COVID-19 pandemic, while the consumption of antivirals for influenza A (H1N1) rose in the post-COVID-19 pandemic period, indicating a minor spike in the occurrence of influenza A (H1N1) after the COVID-19 pandemic. Fever is a significant symptom of COVID-19 and can serve as a reliable indicator of disease prevalence. Our research found that the prevalence of COVID-19 in urban areas was significantly higher (at 78.5 %, 95 % CI: 73.4 % - 83.9 %) than in rural areas (with a prevalence of 48.1 %, 95 % CI: 42.4 % - 53.8 %). The prevalence of COVID-19 in urban areas in this study was consistent with the data reported by the Chinese center for Disease Control and Prevention (82.4 %). Continuous monitoring of WWTPs in urban areas with fluctuating populations and complex demographics can provide early disease warning. Our results demonstrate the feasibility of evaluating community disease prevalence by selecting major therapeutic medicines as biomarkers in wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Antipyretic analgesics are used to manage and control symptoms occurring after vaccination, but may hamper immunogenicity or vaccine efficacy. We examined the association between prophylactic or therapeutic use of antipyretic analgesics and SARS-CoV-2 antibody titers for vaccine recipients. Data were obtained from 1,498 staff members of a medical and research institution in Tokyo, Japan, who had received the second dose of the BNT162b2 vaccine. We quantitatively measured anti-SARS-CoV-2 spike protein IgG titers in the participants three months after vaccination. The prophylactic and therapeutic use of antipyretic analgesics was ascertained via a questionnaire. A linear regression model was used to examine the association between antipyretic analgesic use and log-transformed anti-SARS-CoV-2 spike protein IgG titers. Based on model parameters, we estimated geometric mean titers (GMT) and the corresponding 95 % confidence intervals (CI). The results showed that IgG titers in vaccine recipients who used antipyretic analgesics therapeutically was higher than the titers in those who did not (geometric mean ratio [GMR] = 1.26, 95 % CI = 1.17-1.34) with GMTs being 6,147 (95 % CI = 5,833-6,460) and 4,895 (95 % CI = 4,676-5,115) for those who used antipyretic analgesics therapeutically and those who did not, respectively. The association was attenuated, but remained statistically significant after adjusting for symptoms (GMR = 1.14, 95 % CI = 1.06-1.23). We did not find any evidence of significant association in relation to the prophylactic use of antipyretic analgesics (GMR = 0.96, 95 % CI = 0.84-1.10), with GMTs being 5,245 (95 % CI = 4,577-5,913) and 5,452 (95 % CI = 5,258-5,645) for those who used antipyretic analgesics prophylactically and those who did not, respectively. In conclusion, we did not find any evidence of suppression of the humoral response after the second dose of SARS-CoV-2 vaccination by prophylactic or therapeutic use of antipyretic analgesics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Traditional Chinese medicine (TCM) decoction is a complex polydispersed phase system containing colloid solution, emulsion and suspension, which maybe induced by the supramolecular phenomenon in decoction. However, until now there is no systematic analysis of composition and formation mechanism of supramolecules in TCM decoction contained mineral drug and herb medicines. Maxing Shigan Decoction (MXSGT), one of the classic TCM recipes, has been widely used in the treatment of fever in clinic. In this study, we obtained the supramolecular part of MXSGT (MXSGT NPs). And its traceability, formation mechanism, metal and organic components were further analyzed. The morphology was characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS); and the lipopolysaccharides (LPS) induced rats' fever model was established to evaluate the antipyretic effect of MXSGT NPs. Furthermore, interaction of the disassembled groups was studied to explore the traceability and formation mechanism of MXSGT NPs by isothermal titration calorimeter (ITC). Due to the combination of mineral gypsum and herb medicines, both ICP-OES and UHPLC-Q-Orbitrap HRMS were used to analyze metal and organic components of MXSGT and MXSGT NPs, respectively. The results showed that MXSGT NPs was regular spherical nanoparticles and had the same antipyretic effect as MXSGT. Moreover, MXSGT NPs was formed by the interaction between metal and organic components, resulted in enriching the main active compounds of MXSGT. This study would provide a new idea of studying TCM decoction, especially clarifying the connotation with the participation of mineral gypsum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Purpose: Aim of this study was to evaluated anxiety, depression, and possible negative implications on work activities during the Sars-CoV-2 pandemic, in a group of Multiple Sclerosis (MS) patients at risk of flu-like syndrome (FLS) compared with FLS- free treatments., Methods: The present study included patients treated with interferon-ß (IFNß), glatiramer, and natalizumab for at least one year. Collected data included the diagnosis of COVID-19 infection, Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), together with questions about FLS, change in work habits, use of antipyretics, anxiety, and depression., Results: 100 patients were included in the study. Six patients in IFNß and 5 in the natalizumab group had a confirmed COVID-19 infection. 68% in the IFNß patients reported FLS and only one reported an increase in flu-like frequency during the pandemic; 14% reported lower compliance with treatment, and 40% reported uptake of antipyretics several times. Only one IFNß patient reported having lost more working days than the previous year. The average BAI (p = 0.039) was higher in natalizumab group. Correcting these data by age, sex and EDSS to a multivariate analysis we did not find any statistically significant difference in terms of BAI and BDI-II between the three treatment groups., Conclusions: FLS were not perceived as COVID19-like symptoms but as expected by traditional pharmacological treatments indeed. These data suggest that IFNß can be used safely., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Bupleuri Radix, the dried roots of Bupleurum chinense DC. (BC) or Bupleurum scorzonerifolium Willd., is one of the most frequently used traditional Chinese medicines. As the species in Xiao-Chai-Hu decoction, BC has been used as an antipyretic medicine with a long history. However, its antipyretic characteristics and underlying mechanism(s) remain unclear., Aim of the Study: To elucidate the antipyretic characteristics and mechanism(s) of BC used in its traditional way., Methods: The water extract of BC (BCE) was prepared according to the traditional decocting mode. Murine fever and endotoxemia models were induced by intravenous injection of lipopolysaccharide (LPS). In vitro complement activation assay and the levels of TNF-α, IL-6, IL-1β, and C5a were determined by ELISA., Results: BCE exerted a confirmed but mild antipyretic effect on LPS-induced fever of rat. In vitro, it significantly lowered LPS-elevated TNF-α in the supernatant of rat complete blood cells and THP-1 cells, but failed to decrease IL-6 and IL-1β. In murine endotoxemia models, BCE markedly decreased serum TNF-α, but had no impact on IL-6 and IL-1β. BCE also restricted complement activation in vitro and in vivo. Nevertheless, the mixture of saikosaponin A and D could not suppress supernatant TNF-α of monocytes and serum TNF-α of endotoxemia mice., Conclusions: The present study dissects the peripheral mechanism for the antipyretic effect of BC used in the traditional way. Our findings indicate that BCE directly suppresses monocyte-produced TNF-α, thus decreasing circulating TNF-α, which may be responsible for its mild but confirmed antipyretic action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Multiple plant species are used traditionally in southern Africa to treat fever. This review summarises the traditional use, highlights promising plant species and focuses on validation studies to highlight future areas of research., Aim of the Study: This study aimed to critically review the use of southern African plants to alleviate fever. Additionally, an examination of research into those plants was undertaken to highlight gaps in the literature with the aim of stimulating further research in this field., Materials and Methods: Ethnobotanical books, reviews and primary research studies were searched to identify plant species traditionally used to treat fever in southern Africa and to summarise the current knowledge and identify areas requiring further research. This study was non-biased and did not have any taxonomic preferences, nor did it favour any southern African healing systems over the others., Results: The traditional therapeutic uses of 203 southern African plant species to alleviate fever were recorded. Leaves and roots/bulbs/rhizomes were the most commonly used plant part, and they were most commonly prepared as decoctions or infusions and consumed orally. Notably, only twenty-two species (∼11% of the identified species) have been scientifically evaluated for antipyretic properties, with substantially fewer mechanistic studies evident., Conclusions: Despite the availability of ethnobotanical records, the antipyretic properties of southern African medicinal plants are poorly reported. Indeed, the efficacy of most plants is yet to be verified and very few mechanistic studies are available., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In spite of the progress in medical science in our country during recent years, the investigation of some problems of development and course of acute glomerulonephritis (AG) particularly in young adults remains topical. In this paper we discuss classical types of AG in young adults, when the intake of paracetamol and diclofenac led to a dysfunctional and organic liver injury, at the same time it negatively affected the course of AG. Goal - assessment of cause-and-effect relations of renal and liver injuries in young adults with acute glomerulonephritis. To achieve the goals of the research we examined 150 male patients with AG, aged 18-25. According to clinical presentations all the patients were divided into two groups. In the first group (102 patients) the disease manifested with acute nephritic syndrome; in the second group of patients (48 patients) - with isolated urinary syndrome. Out of 150 patients examined for AG 66 had subclinical liver injury, which resulted from the effect of antipyretic hepatotoxic drugs taken in the initial stage of the disease. Due to the toxic and immunological liver injury, levels of transaminases increase, and albumin levels decrease. These changes occur along with the development of AG and are correlated with some laboratory values (ASLO, CRP, ESR, hematuria), the injury is more evident when etiological factor is the streptococcal infection. In AG liver injury has a toxic allergic character and is more expressed in post streptococcal glomerulonephritis. Frequency of liver injury depends on specific features of a particular organism; it does not depend on the dose of the taken drug. In case of any type of AG it is necessary to assess the functional state of liver and after the treatment of the main disease hepatologist follow-up of patients is recommended.

Antimicrobial resistance has been considered as a great threat to biosecurity and human health. And the transmission of antibiotic resistance genes (ARGs) by conjugated plasmid is a key factor in the prevalence of antimicrobial resistance. Paracetamol (PRC), one of nonopioid analgesics, is an extensively used antipyretic and mild analgesic worldwide available for numerous prescriptions. It was unclear whether PRC could promote the spread of ARGs. Here, it was demonstrated that PRC promoted intergenera conjugative plasmid transfer in an established conjugation model. Both donor and recipient strains treated by PRC emerged the variations of reactive oxygen species (ROS), SOS response and cell membrane permeability. Correspondingly, transcriptome analysis revealed that the gene expression involved in cell membrane permeability and SOS response was up-regulated significantly after PRC exposure. More directly, PRC also increased the expressions of conjugation related genes of trbG and trbP in donor. This study proved for the first time that PRC could enhance the intergenera conjugative plasmid transfer. Collectively, these findings manifested the potential threat associated with the existence of non-antibiotic substance PRC, which could provide an important insight into antimicrobial resistance spread., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fever in children is one of the most common symptoms of pediatric diseases and the most common complaint in pediatric clinics, especially in the emergency department. Diseases such as pneumonia, sepsis, and meningitis are leading causes of death in children, and the early manifestations of these diseases are accompanied by fever symptoms. Accurate diagnosis and real-time monitoring of the status of febrile children, rapid and effective identification of the cause, and treatment can have a positive impact on relieving their symptoms and improving their quality of life. In recent years, wearable diagnostic sensors have attracted special attention for their high flexibility, real-time monitoring, and sensitivity. Temperature sensors and heart rate sensors have provided new advances in detecting children's body temperature and heart rate. Furthermore, some novel formulations have also received wide attention for addressing bottlenecks in medication administration for febrile children, such as difficulty in swallowing and inaccurate dosing. In this context, the present review provides recent advances of novel wearable medical sensor devices for diagnosing fever. Moreover, the application progress of innovative dosage forms of classical antipyretic drugs for children is presented. Finally, challenges and prospects of wearable sensor-based diagnostics and novel agent-based treatment of fever in children are discussed in brief., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Pneumonia is a major research core topic in the medical field, and clinical trials of pneumonia and respiratory tract infection have been ongoing. The purpose of this study was to investigate the clinical efficacy and safety of Shuanghuanghua granules in the treatment of pneumonia and respiratory tract infection based on NMR molecular imaging, and to lay a foundation for the development of new drugs. In this paper, 126 patients were randomly divided into the control group, the treatment group 1, the and treatment group 2, and were given Fengreganmao granules, Shuanghuanghua granules (ultrafine preparation), and Shuanghuanghua granules (extract preparation), respectively. The main symptom scores, sign scores, antipyretic time, and virus content before and after treatment were recorded. Statistical analysis was carried out on this basis. The experiment showed that the body temperature of the subjects in the three groups before treatment was: control group (37.59 ± 0.78), treatment group 1 (37.8 ± 0.81), and treatment group 2 (37.6 ± 0.76). After treatment, the body temperature of subjects in the three groups was: control group (36.67 ± 0.71), treatment group 1 (36.49 ± 0.43), and treatment group 2 (36.19 ± 0.25). Experiments show that Shuanghuanghua granules can significantly reduce the nasal virus, adenovirus, parainfluenza virus, etc. in the patient's body. And it can shorten the antipyretic time of patients and has good clinical application. In addition, this study gave full play to the role of MRI molecular imaging and provided ideas and references for the clinical treatment of pneumonia and respiratory tract infection., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Lili Jiang et al.)

This review is a systematic scientific work on medicinal and traditional use, on the chemical composition of specialized metabolites, volatile and non-volatile, on aspects related to toxicology and phytotherapy of Nigella damascena L. The genus Nigella (Ranunculaceae) is distributed throughout the Mediterranean basin, extending to northern India, and has been divided into three sections. Nigella damanscena L. is traditionally used as an ingredient in food, for example, as flavouring agents in bread and cheese, but is also known in folk medicine, used to regulate menstruation; for catarrhal affections and amenorrhea; as a diuretic and sternutatory; as an analgesic, anti-oedematous, and antipyretic; and for vermifuge and its disinfectant effects. This paper reviews the most dated to the latest scientific research on this species, highlighting the single isolated metabolites and exploring their biological activity. Fifty-seven natural compounds have been isolated and characterised from the seeds, roots, and aerial parts of the plant. Among these constituents, alkaloids, flavonoids, diterpenes, triterpenes, and aromatic compounds are the main constituents. The isolated compounds and the various extracts obtained with solvents of different polarities presented a diverse spectrum of biological activities such as antibacterial, antifungal, antitumour, antioxidant, anti-inflammatory, antipyretic, anti-oedema, and antiviral activities. Various in vitro and in vivo tests have demonstrated the pharmacological potential of β-elemene and alkaloid damascenin. Unfortunately, the largest number of biological studies on this species and its metabolites have been conducted in vitro; therefore, further investigation is necessary to evaluate the toxicological aspects and real mechanisms of action of crude extracts to confirm the therapeutic potential of N. damascena., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The present paper presents results of analgesic, antipyretic activity and anti-inflammatory potential of extract obtained from Acacia cyanophylla when tested at different doses. Analgesic potential of the crude methanolic extract tested by acetic acid assay was dose dependent and maximum activity of 61.60% was measured at 400 mg/kg. Analgesic activity by hot plate method revealed that maximum activity of 36.98% was noted when the mice were exposed to 90 minutes at higher dose of 400 mg/kg. Similar pattern for antipyretic activity was observed as noted for analgesic activity. Anti-inflammatory activity was dose and time dependent when evaluated by Carrageenan-induced paw edema and Xylene-induced ear edema model. Maximum anti-inflammatory activity (43.32%) was shown by crude methanolic extract of Acacia cyanophylla at 400mg/kg -1 after 5 hours on Carrageenan-induced paw edema model. Similarly, maximum (68.80%) anti-inflammatory activity was noted when accessed by Xylene-induced ear edema model at the dose of 200mg/kg after 60 minutes. No in vivo toxicity of the extracts up to the dose of 2000mg/kg was observed using albino mice.

Background: The reactogenicity of BNT162b2 COVID-19 vaccine has been commonly reported and antipyretic medications are often used for mitigating adverse reactions. Possible associations between the reactogenicity events and specific antibody responses have not been fully investigated, nor has the influence of using antipyretics., Methods: Serum samples were collected from hospital healthcare workers with no COVID-19 history and the SARS-CoV-2 spike-specific IgG titer after two doses was measured. Degree of solicited adverse reactions in a day, including the highest body temperature, were reported using a self-reporting diary for five days after each dose. The highest body temperature during the five days was divided into three grades (<37.0 °C, 37.0-37.9 °C, or ≥ 38.0 °C). Self-medicated antipyretics were reported using a questionnaire., Results: The data of 335 participants were available for analysis. Multivariate analysis extracted the fever grade after the second dose (standardized coefficient beta = 0.301, p < 0.0001), female sex (beta = 0.196, p = 0.0014), and age (beta = -0.119, p = 0.0495) as being significantly correlated with the IgG titers. The positive correlation of the fever grade after the second dose with the IgG titers was also observed when analyzed by sex and age. The use of antipyretics did not interfere with the IgG titers irrespective of the fever grade., Conclusions: The fever intensity after the second dose was associated with the IgG titer and antipyretic medications may be beneficial to mitigate the suffering from adverse reactions, without interfering with the acquisition of sufficient antibody responses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tardigrades in their natural environment are exposed to various environmental toxicants, including non-steroidal anti-inflammatory drugs (NSAIDs) or antipyretics such as paracetamol. This drug can enter the animal's body through the body wall or the digestive system with food and can affect the biology of organisms. In this paper, we report for the first time the effects of paracetamol on tardigrade storage cells. We analyzed the effects of short-term (7 days) and long-term (28 days) exposure of Hypsibius exemplaris storage cells to three paracetamol concentrations (0.2 µgxL−1, 230 µgxL−1, 1 mgxL−1). Our results showed that increasing paracetamol concentration and incubation time increases the number of damaged mitochondria in storage cells, and autophagy is activated and intensified. Moreover, the relocation of some organelles and cell deformation may indicate cytoskeleton damage. [ABSTRACT FROM AUTHOR]

Objectives: Fever is a common symptom among children. Parental lack of knowledge about fever could cause anxiety and lead to unnecessary measures to subside fever. There is little evidence about German parents' knowledge and their fever management., Design: A cross-sectional study using a paper-based questionnaire., Setting: 16 kindergartens in Saarbrücken and Saarlouis regional association accepted to participate in the study. Parents from these kindergartens were requested during the pickup time to answer the questionnaire., Participants: 481 German parents participated in the study, 394 of them were women. Inclusion criteria were good understanding of German and being a parent of at least one child below the age of 7 years., Primary and Secondary Outcome Measures: Knowledge and behaviour of parents on paediatric fever management and the factors influencing fever anxiety., Results: The older the parents were, the more anxiety they reported. Their definition of fever had a wide range of 30°C-41°C (mean 38.46, SD=0.67) and almost 90% (mean 3.05, SD=2.03) of participants reported fever as useful, whereby they felt more confident the more they found fever useful. 69% of parents felt calm when their child has fever (mean 4.47, SD=2.27). In case of fever, 55% of parents administer paracetamol, 72% ibuprofen and 32% of them would alternate between the two. Paracetamol and ibuprofen are used more by more anxious parents. In explorative factor analysis, reasons to reduce temperature were summarised in three main factors: damage prevention, illness control and well-being protection, whereby the first two were positively related to parental anxiety., Conclusions: Both knowledge as well as level of confidence/anxiety vary largely. Taking antipyretics is related to higher level of anxiety, indicating the need for further education. Fever anxiety depends on multiple factors, which have to be further investigated., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Over-the-counter (OTC) drugs are becoming increasingly popular. However, little is known about parents' practices concerning the use of OTC antipyretics in children. This paper aimed to study the habits and knowledge of parents regarding the use of OTC antipyretics in their offspring, considering the demographic and socioeconomic characteristics of the families., Material and Methods: A multiple-purpose survey was conducted anonymously among 229 parents of patients hospitalised in the Department of Paediatrics, University Children's Hospital, Krakow. Each parent answered 23 questions regarding OTC antipyretics use in his/her hospitalised child throughout the whole child's life. The data was statistically analysed., Results: OTC antipyretics are administered to their children by 92% of parents. In the vast majority (87%), health care professionals or a leaflet were the sources of information on the drug and its dosage. Parents also used information from TV or the Internet (27%) and friends and family (30%), especially those in the younger age group. Families with high socioeconomic status were more likely to use health care professionals' advice for drug knowledge. Parents of children with allergic diseases made less use of nonmedical sources of knowledge., Conclusions: The majority of parents use OTC antipyretic drugs in their children. However, a high percentage of people using nonmedical sources of information is of concern. It is necessary to educate caregivers and to build the parents' awareness that they take an active role in their child's treatment. It would be useful to create generally available recommendations for home treatment., (© 2021 Olga Pyznar et al. published by Sciendo.)

Paracetamol, one of the most widely used pain-relieving drugs, is deacetylated to 4-aminophenol (4-AP) that undergoes fatty acid amide hydrolase (FAAH)-dependent biotransformation into N-arachidonoylphenolamine (AM404), which mediates TRPV1-dependent antinociception in the brain of rodents. However, paracetamol is also converted to the liver-toxic metabolite N-acetyl-p-benzoquinone imine already at therapeutic doses, urging for safer paracetamol analogues. Primary amine analogues with chemical structures similar to paracetamol were evaluated for their propensity to undergo FAAH-dependent N-arachidonoyl conjugation into TRPV1 activators both in vitro and in vivo in rodents. The antinociceptive and antipyretic activity of paracetamol and primary amine analogues was examined with regard to FAAH and TRPV1 as well as if these analogues produced acute liver toxicity. 5-Amino-2-methoxyphenol (2) and 5-aminoindazole (3) displayed efficient target protein interactions with a dose-dependent antinociceptive effect in the mice formalin test, which in the second phase was dependent on FAAH and TRPV1. No hepatotoxicity of the FAAH substrates transformed into TRPV1 activators was observed. While paracetamol attenuates pyrexia via inhibition of brain cyclooxygenase, its antinociceptive FAAH substrate 4-AP was not antipyretic, suggesting separate mechanisms for the antipyretic and antinociceptive effect of paracetamol. Furthermore, compound 3 reduced fever without a brain cyclooxygenase inhibitory action. The data support our view that analgesics and antipyretics without liver toxicity can be derived from paracetamol. Thus, research into the molecular actions of paracetamol could pave the way for the discovery of analgesics and antipyretics with a better benefit-to-risk ratio., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Geographical variance in the incidence of type 1 diabetes mellitus (T1DM) and its etiological link to viruses and gut microbiome imply causative environmental agents. Antipyretics and especially acetaminophen received some attention recently due to the associations with some autoimmune conditions and lack of studies on the mechanisms influencing the immune system. A couple of recent studies involving large cohorts have found no association between the use of acetaminophen in early childhood and seroconversion leading to T1DM (TEDDY, involving international cohort) or diagnosis of overt T1DM (Norwegian MoBa) in the follow up years. The paper gives the supplemental argumentation for the antipyretic hypothesis presented in Medical Hypotheses in 2016 that is still valid in face of the mentioned conclusions. The hypothesis assumes that critical effect of acetaminophen and possibly other antipyretics expresses itself as the immediate influence on the immune system in the unfortunate coincidence with the other environmental factors, supposedly involving feverish, new to immunity, viral infection, all creating triggering circumstances regardless of age. Young age, in this respect should be regarded as a risk factor due to immatureness of immunity. The paper discusses that antipyretics and particularly acetaminophen need more attention evaluating their possible immunity modulations during infection or through negative effects on intestinal microbiota or both., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Low levels of brain-derived neurotrophic factor (BDNF), a key regulator of synaptic plasticity, are associated with neurological diseases, including depression and Alzheimer's disease. Therefore, BDNF is a drug target for these diseases. Here we screened for inducers of neuronal Bdnf expression from a pharmacologically validated compound library using our recently developed screening assay based on luciferase activity in cultured cortical neurons. We identified 18 pharmacologically validated compounds, most of which were inferred to induce Bdnf expression by their validated pharmacological actions, such as G s -coupled receptor activation or neuronal excitation. Unexpectedly, the screening assay identified the antipyretic drug, dipyrone, to increase Bdnf expression. Dipyrone induced endogenous Bdnf expression by Ca 2+ influx evoked via L-type voltage-dependent Ca 2+ channels and the N-methyl-d-aspartate receptor, indicating that dipyrone induced activity-regulated Bdnf expression in neurons. However, dipyrone-induced Bdnf expression is independent of validated pharmacological effects. Although our screening assay is difficult to reveal how active compounds induce Bdnf expression, this method is convenient to identify inducers of Bdnf expression in primary neurons. Our screening assay evaluated neuronal BDNF induction and can be used to screen for drug re-positioning, as well as novel candidate drugs, for neurological diseases that have low levels of BDNF in the brain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Reduning injection (RDN), a patented traditional Chinese medicine, has the obvious antipyretic effect and has been widely used in China. Although some previous studies proved its antipyretic effect by animal efficacy experiment or clinical observation, its holistic mechanism in vivo was still unclear., Aim of the Study: To comprehensively elucidate the antipyretic mechanism of RDN, the investigation of fever-related potential biomarkers and metabolic pathways in the rat fever model is described in this paper., Materials and Methods: Rat fever model was established by dry yeast. A large number of endogenous metabolites in serum and urine were detected by UPLC-Q-TOF/MS, and fever-related potential biomarkers were screened and identified by multivariate analysis and metabolite databases. The reliability and biological significance of the largely disturbed biomarkers was verified by the metabolic network and the correlation with pharmacodynamic indicators, which contained IL-1β, IL-6, TNF-α, PGE 2 and cAMP., Results: The established UPLC-Q-TOF/MS analytical method afforded satisfactory results in terms of precision, repeatability and stability, which met the requirements of biological sample determination. A total of 32 potential biomarkers associated with fever were screened and identified, among which 22 species could be adjusted by RDN. The metabolism pathway analysis revealed that valine, leucine and isoleucine biosynthesis, and sphingolipid metabolism were greatly disturbed. Their biomarkers involved L-leucine, L-valine, sphinganine and phytosphingosine, all of which showed a callback trend after RDN was given. These 4 biomarkers had a certain correlation with some known fever-related small molecules and pharmacodynamic indicators, which indicated that the selected fever-related biomarkers had certain reliability and biological significance., Conclusions: RDN has a good regulation of the metabolic disorder of endogenous components in dry yeast-induced fever rats. Its antipyretic mechanism is mainly related to the regulation of amino acid, lipid and energy metabolism. The study is useful to better understand and analyze the pharmacodynamic mechanism of complex systems, such as traditional Chinese medicine., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: The use of antipyretics to manage the febrile child is becoming increasingly popular. Paracetamol and ibuprofen are the most commonly used interventions to manage fever in children; however, there have been no comparative analyses. The aim of the study is to evaluate the evidence comparing paracetamol to ibuprofen in the treatment of fever in children., Methods: A systematic review of randomised controlled trials investigating the administration of oral paracetamol and ibuprofen to reduce fever in children. Children aged 1 month to 12 years with a temperature between 37.5 and 41°C were included. A total of 3023 papers were identified. After removal of duplications, application of inclusion criteria and screening, eight papers were subjected to critical appraisal and included in this study., Results: Six of the studies identified that ibuprofen was slightly, but not significantly, better at reducing fever in children than paracetamol. Dosage variances and route of temperature measurement ranged between studies, limiting the comparability of studies. While ibuprofen was reported to be marginally more effective at reducing fever and fever associated discomfort in children, there is insufficient data to conclude that ibuprofen is superior to paracetamol., Conclusion: There is little evidence supporting the superior efficacy of paracetamol or ibuprofen in the treatment of fever in children with indications that both drugs are equally effective., (© 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Qingkailing injection (QKLI) has a notable antipyretic effect and is widely used in China as a clinical emergency medicine. To elucidate the pharmacological action thoroughly, following the investigation of the urine metabolome and hypothalamus metabolome, plasma metabolomics combined with lipidomics profiling of the QKLI antipyretic effect in a rat model is described in this paper. Compared with pure metabolomics profiling, this non-targeted plasma metabolomics combined with lipidomics profiling based on ultra-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS) could be used for a large-scale detection of features in plasma samples. The results showed that 15 metabolites at the 1 h time point and 19 metabolites at the 2 h time point after QKLI administration were associated with the antipyretic effect of QKLI, including amino acid, phosphatidylcholine and lysophosphatidylcholine. The metabolism pathway analysis revealed that the potential biomarkers, which were important for the antipyretic mechanism of QKLI, were closely responsible for correcting the perturbed pathways of amino acid metabolism and lipid metabolism. In conclusion, the use of complementary UPLC Q-TOF/MS based metabolomics and lipidomics allows for the discovery of new potential plasma biomarkers in the QKLI antipyretic process and the associated pathways, and aided in advancing the understanding of the holism and synergism of the Chinese drug., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Postoperative opioid use can lead to dependence, contributing to the opioid epidemic in the United States. New persistent opioid use after minor surgeries occurs in 5.9% of patients. With increased documentation of persistent opioid use postoperatively, surgeons must pursue interventions to reduce opioid use perioperatively. We performed a prospective cohort study to assess the feasibility of a preoperative intervention via patient education or counseling and changes in provider prescribing patterns to reduce postoperative opioid use. We included adult patients undergoing thyroidectomy and parathyroidectomy from January 22, 2019 to February 28, 2019 at a tertiary referral, academic endocrine surgery practice. Surveys were administered to assess pain and patient satisfaction postoperatively. Prescription, demographic, and comorbidity data were collected from the electronic health record. Sixty six patients (74.2% women, mean age 58.6 [SD 14.9] y) underwent thyroidectomy (n = 35), parathyroidectomy (n = 24), and other cervical endocrine operations (n = 7). All patients received a preoperative educational intervention in the form of a paper handout. 90.9% of patients were discharged with prescriptions for nonopioid pain medications, and 7.6% were given an opioid prescription on discharge. Among those who received an opioid prescription, the median quantity of opioids prescribed was 135 (IQR 120-150) oral morphine equivalents. On survey, four patients (6.1%) reported any postoperative opioid use, and 94.6% of patients expressed satisfaction with their preoperative education and postoperative pain management. Clear and standardized education regarding postoperative pain management is feasible and associated with high patient satisfaction. Initiation of such education may support efforts to minimize unnecessary opioid prescriptions in the population undergoing endocrine surgery. • Standardizing post-op pain med prescribing to emphasize non-opioid analgesics is feasible. • This can reduce the amount of postoperative opioids used. • High patient satisfaction with non-opioid postop pain management with pre-op education. [ABSTRACT FROM AUTHOR]

Linarin is a flavone glycoside in the plants Flos chrysanthemi indici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii, and has been reported to possess analgesic, antipyretic, anti-inflammatory and neuroprotective activities. In this paper, linarin was investigated for its AChE inhibitory potential both in-vitro and ex-vivo. Ellman's colorimetric method was used for the determination of AChE inhibitory activity in mouse brain. In-vitro assays revealed that linarin inhibited AChE activity with an IC50 of 3.801 ± 1.149 µM. Ex-vivo study showed that the AChE activity was significantly reduced in both the cortex and hippocampus of mice treated intraperitoneally with various doses of linarin (35, 70 and 140 mg/Kg). The inhibition effects produced by high dose of linarin were the same as that obtained after huperzine A treatment (0.5 mg/Kg). Molecular docking study revealed that both 4'-methoxyl group and 7-O-sugar moiety of linarin played important roles in ligand-receptor binding and thus they are mainly responsible for AChE inhibitory activity. In view of its potent AChE inhibitory activity, linarin may be a promising therapeutic agent for the treatment of some diseases associated with AChE, such as glaucoma, myasthenia gravis, gastric motility and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

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Highlights • An active surveillance found the 4CMenB vaccine to frequently cause fever and injection site reactions. • These adverse events resulted in absenteeism or medical consultations in 6.2% to 9.2% after dose 1 and 2. • Among children <10 years old, acetaminophen prophylaxis significantly reduced fever incidence. Abstract Background To address a high incidence of serogroup B invasive meningococcal disease (IMD-B) in the Saguenay–Lac-Saint-Jean region, Quebec, Canada, a mass vaccination campaign targeting nearly 60,000 individuals ≤20 years old was launched in May 2014. Because of the limited clinical experience with the four-component meningococcal B vaccine (4CMenB), active surveillance for adverse events following immunization (AEFI) was conducted. This paper reports 4CMenB AEFI surveillance findings. Methods Active surveillance assessed AEFIs with acute onset within 7-days post-immunization, AEFI-associated absenteeism and medical consultations, impact of antipyretic prophylaxis and coadministration of other vaccines. Results By July 17, 2015, 83% and 77% of the 59,098 individuals targeted by the campaign had received a first and a second dose of 4CMenB. The incidence of fever on days1-2 was highest in children <2 years old but only 0.6% reported a temperature ≥40◦C. Among children <10 years old, ≥2doses of acetaminophen prophylaxis significantly reduced fever incidence on days1-2 after dose1&2. Absenteeism or a medical consultation during the 7 days following vaccination was reported by 6.2% of vaccinees post-dose1 and 9.2% post-dose2 and was most often reported in association with fever/malaise (4.2%) or injection site reactions (3.6%). Conclusion Large-scale population-based surveillance identified a 7-day reactogenicity profile consistent with earlier clinical trials with the 4CMenB vaccine but indicating frequent AEFI-associated absenteeism and medical consultations affecting the societal cost of this vaccine. We conclude acceptable vaccine safety and risk-benefit profile overall on the short term, particularly as an intervention to address a high regional incidence of IMD-B. [ABSTRACT FROM AUTHOR]

The appendix of the Sauromatum senosum inflorescence is a striking example of thermogenesis in plants. On the day of opening, the Sauromatum appendix becomes hot, reaching up to 32 °C. Aspirin, salicylic acid and 2,6‐dihydroxybenzoic acid, a subclass of NSAIDs, induce a temperature rise from three mitochondrial sources: alternative oxidase, F1FO‐ATP synthase and adenine nucleotide translocator. This temperature rise is synchronized and compounded under various light/dark regimes. We studied the effect of different subgroups of NSAIDs on the temperature rise.Tissue slices of appendix of Sauromatum and Arumitalicum inflorescences at a pre‐mature stage were treated with the three inducers in combination with one NSAID under constant light or darkness and under different photoperiods.Temperature rise generated by the three heat sources in the presence of inducers and different non‐selective NSAIDs were not compounded and occurred at three different times. Under constant light, DuP‐697, ibuprofen, flurbiprofen, acetaminophen and diclofenac suppressed the temperature rise induced by the three salicylates. Desynchronization and delayed temperature rise were detected with 6/42‐h light/ dark and 15/33‐h light/dark regimes in the presence of celecoxib and ibuprofen. With a 24/24‐h light/dark regime, temperature rise was suppressed in the presence of ibuprofen. There were differences in response to individual NSAIDs between appendix tissue of A. italicum and S. venosum.Mitochondrial energy balance is affected by NSAIDs. There is an interaction between light/dark regime and temperature rise and a relationship between timing mechanism and temperature rise. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization's case definition for influenza‐like illness (ILI) includes a measured temperature of ≥38°C. We conducted this study to assess the effect of antipyretics on performance of ILI surveillance in Ghana. Methods: A cross‐sectional study was conducted in two districts of Ghana from September 2013 to May 2014. We collected epidemiological data and respiratory specimens from an expanded ILI case definition, which included patients presenting to health facilities with measured temperature ≥38°C or reported fever (but afebrile at the time of evaluation), and cough, with onset in the last 10 days. Specimens were tested for influenza viruses by real time reverse‐transcription polymerase chain reaction. Results: Of 321 participants who met our expanded ILI case definition, 236 presented with temperature of <38°C but reported subjective fever. Of these, 17% (39/236) were positive for influenza virus; Of those with fever ≤38°C who took antipyretics, 21%(16/77) were positive for influenza, compared with 14%(23/159) of those who did not take antipyretics. The addition of subjective fever to the standard ILI case definition captured approximately an additional 57% influenza cases but also required testing of approximately four times as many patients. However, including those without fever on presentation that had taken antipyretics found an additional 23% of Influenza cases and only two times as much testing. Conclusion: Depending on the goals of surveillance (monitoring virus circulation or determining disease burden) and available resources, a more sensitive case definition including subjective fever and history of use of antipyretics may be warranted. [ABSTRACT FROM AUTHOR]

Parcetamol is one of the most popular analgesic and antipyretic drugs. The existence of this drug in different pharmaceutical forms makes it even easier to use it at different ages. It is considered first-line treatment in children, for the treatment of pain and fever. With its widespread use, it has become one of the most common pharmaceuticals associated with accidental poisoning. Infants and children are particularly susceptible to acute overdose of paracetamol, which often causes: hepatotoxicity, hypothermia, thrombocytopenia, leukopenia, respiratory side effects, etc. In 80% of the presented cases, paracetamol was used for fever, therefore hypothermia is one of the most expressed symptoms. The main purpose of this study is to identify toxic doses of paracetamol in children, symptoms, management and treatment of these poisonings. From this research, in a single pediatric clinic, many paracetamol intoxications have occurred due to parents' mistakes, therefore these mistakes should be made known to the public in order to be avoided by others. [ABSTRACT FROM AUTHOR]

Tremendous efforts in research without a conclusion on the cause of type 1 diabetes allow the presumption that there is still a blind spot in the development of T1D that is not covered by current hypotheses. The review of geographical knowledge suggests that there is a well-expressed anthropogenic element within the complex environmental trigger of T1D. On the other hand, the initiation of T1D's directed autoimmunity is temporally related to the organism's immune response, induced by entero-viruses, most expectedly. Consequently, the searched for anthropogenic environmental factor is a player temporally linked to enteroviral infections. This paper discusses the participation of antipyretic medicines, and especially paracetamol, with a whole century's history of growing sales and popularity, including indirect influence through phenacetin during the first half of the 20th century. As proposed by several independent studies, the use of pharmaceuticals to reduce fever may counteract with the protective features of the immune system and create favourable conditions for a virus to spread within the organism and damage specific tissue. A preliminary comparison of paracetamol sales with the incidence of T1D data in Lithuania and the other countries in the North-eastern Baltic region supports this hypothesis. [ABSTRACT FROM AUTHOR]

Background: Malaria remains a major public health challenge in Africa where annually, ~250,000 children with malaria experience a neurologic injury with subsequent neuro-disability. Evidence indicates that a higher temperature during the acute illness is a risk factor for post-infectious neurologic sequelae. As such, aggressive antipyretic therapy may be warranted among children with complicated malaria at substantial risk of brain injury. Previous clinical trials conducted primarily in children with uncomplicated malaria and using only a single antipyretic medication have shown limited benefits in terms of fever reduction; however, no studies to date have examined malaria fever management using dual therapies. In this clinical trial of aggressive antipyretic therapy, children hospitalized with central nervous system (CNS) malaria will be randomized to usual care (acetaminophen every 6 hours for a temperature ≥ 38.5°C) vs. prophylactic acetaminophen and ibuprofen every 6 hours for 72 hours. Methods: In this double-blinded, placebo controlled, two-armed clinical trial, we will enroll 284 participants from three settings at Queen Elizabeth Central Hospital in Blantyre, Malawi; at the University Teaching Hospitals Children's Hospital in Lusaka, Zambia and at Chipata Central Hospital, Chipata, Zambia. Parents or guardians must provide written informed consent. Eligible participants are 2–11 years with evidence of P. falciparum malaria infection by peripheral blood smear or rapid diagnostic test with CNS symptoms associated with malaria. Eligible children will receive treatment allocation randomization either to standard of care for fever management or to prophylactic, scheduled treatment every 6 hours for 72 hours with dual antipyretic therapies using acetaminophen and ibuprofen. Assignment to treatment groups will be with 1:1 allocation using blocked randomization. The primary outcome will be maximum temperature in the 72 hours after enrolment. Secondary outcomes include parasite clearance as determined by quantitative Histidine Rich Protein II and seizures through 72 hours after enrolment. Discussion: This clinical trial seeks to challenge the practice paradigm of limited fever treatment based upon hyperpyrexia by evaluating the fever-reduction efficacy of more aggressive antipyretic using two antipyretics and prophylactic administration and will elucidate the impact of antipyretics on parasite clearance and acute symptomatic seizures. If aggressive antipyretic therapy is shown to safely reduce the maximum temperature, a clinical trial evaluating the neuroprotective effects of temperature reduction in CNS malaria is warranted. [ABSTRACT FROM AUTHOR]

The application of aspirin-like drugs in modern medicine is very broad, encompassing the treatment of inflammation, pain and a variety of cardiovascular conditions. Although anecdotal accounts of willow bark extract as an anti-inflammatory drug have occurred since written records began (for example by Hippocrates), the first convincing demonstration of a potent anti-pyretic effect of willow bark containing salicylates was made by the English cleric Edward Stone in the late eighteenth century. Here, we discuss the route to optimizing and understanding the mechanism of action of anti-inflammatory drugs that have their origins in Stone's seminal study, 'An account of the success of the bark of the willow in the cure of agues'. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. [ABSTRACT FROM AUTHOR]