Antipyretic effect of oral dipyrone (Metamizole) compared to oral ibuprofen in febrile children: a systematic review and meta-analysis.

BACKGROUND: Dipyrone (Metamizole) is a potent pain reliever and fever reducer with muscle relaxant properties, most commonly used as an analgesic and antipyretic agent. Despite the fact that it has been banned in many high-income countries following confirmed studies of fatal agranulocytosis and adverse drug reactions, it is still widely used in various countries of the world. However, the antipyretic therapeutic indications of dipyrone in febrile children are currently unknown, and there is little information on the advantages and disadvantages of using dipyrone in febrile children. In febrile children, we expected that dipyrone's antipyretic effectiveness wouldn't be any more effective than ibuprofen. Therefore, the purpose of this research is to evaluate the effectiveness of oral dipyrone and oral ibuprofen as antipyretics in febrile children. METHODS: Several databases, including PubMed, Scopus, Web of Science, and Cochrane Library, were searched thoroughly using a pre-established search strategy for potential research. The studies included in this analysis comprised randomized controlled trials that compared the antipyretic effects of oral ibuprofen and oral dipyrone in febrile children. Data analysis was carried out using RevMan 5.4 software. RESULTS: Three studies were selected among the 27 publications we discovered to be applicable, and they underwent qualitative and quantitative analysis. The pooled analysis revealed no discernible difference between oral dipyrone and oral ibuprofen in terms of their antipyretic effects (Mean difference (MD) = 0.06; 95% confidence interval (CI): -0.08, 0.20). CONCLUSION: Both oral dipyrone and ibuprofen are effective in reducing high-temperature levels in febrile children without any significant difference.

Short-term Dual Therapy or Mono Therapy With Acetaminophen and Ibuprofen for Fever: A Network Meta-Analysis.

CONTEXT: There is uncertainty whether acetaminophen and ibuprofen are similar in their effects and safety when used as single or dual (alternating or combined) therapies. OBJECTIVE: To assess the comparative efficacy of acetaminophen, ibuprofen alone, alternating, or combined through a systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, and CENTRAL from inception to September 20, 2023. STUDY SELECTION: Randomized trials comparing acetaminophen, ibuprofen, both alternating, and both combined, for treating children with fever. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model. RESULTS: We included 31 trials (5009 children). We found that combined (odds ratio [OR], 0.19; confidence interval [CI], 0.09-0.42) and alternating therapies (OR, 0.20; CI, 0.06-0.63) may be superior to acetaminophen, whereas ibuprofen at a high dose may be comparable (OR, 0.98; CI, 0.63-1.59) in terms of proportion of afebrile children at the fourth hour. These results were similar at the sixth hour. There were no differences between ibuprofen (low or high dose), or alternating, or combined with acetaminophen in terms of adverse events. LIMITATIONS: We only evaluated the efficacy and safety during the first 6 hours. CONCLUSIONS: Dual may be superior to single therapies for treating fever in children. Acetaminophen may be inferior to combined or alternating therapies to get children afebrile at 4 and 6 hours. Compared with ibuprofen, acetaminophen was also inferior to ibuprofen alone at 4 hours, but similar at 6 hours. PROSPERO registration: CRD42016035236.

Definition and assessment of fever-related discomfort in pediatric literature: a systematic review.

Guidelines advocate that the symptomatic management of fever should prioritize alleviating the child's discomfort. We investigated the definition and assessment of discomfort in febrile children within the scientific pediatric literature. A systematic review was conducted in accordance with PRISMA 2020 guidelines and preregistered on the Prospero database (CRD42023471590). Databases including PubMed, Embase, and Cochrane were searched. Studies addressing discomfort in febrile children were eligible. Out of 794 initially identified articles, 27 original studies and seven guidelines specifically used the term 'discomfort'. Only 14 original articles provided a definition of discomfort, revealing substantial heterogeneity and no clear-cut definition. Discomfort was often assessed subjectively, predominantly through parent or self-report, and only two studies used a scoring system for assessment. The definitions varied widely, with terms such as crying, irritability, shivering and chills, pain and distress, goosebumps commonly used and evaluation of observable modifications such as facial modifications. Overall, no consensus on a single, standardized definition was available. CONCLUSIONS: This systematic review shows the absence of a standardized definition and assessment of discomfort in febrile children. The findings of the present analysis might be the basis for building a consensus and developing a new tool to evaluate discomfort. WHAT IS KNOWN: • Discomfort is currently considered the main criterion to guide antipyretic administration in children with fever. • Despite this clear-cut recommendation, it has been questioned whether a commonly accepted understanding and assessment of this condition exists. WHAT IS NEW: • This systematic review identifies a significant heterogeneity in definitions and assessment of discomfort in children with fever. • Both subjective parameters and observable modifications in physiological parameters should be included in a new and shared characterization of discomfort.

Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria: A Randomized Clinical Trial.

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.

Rectal versus intravenous administration of acetaminophen; Clinical investigation of plasma level, analgesic, and antipyretic effects on 6-month to 6-year-old children in Zabol city, Iran.

OBJECTIVES: Acetaminophen is the most widely antipyretic analgesic medicine used in adults and children worldwide. Rectal acetaminophen is widely used in children who resist or cannot take oral medications. This study was designed to compare the efficacy of rectal and IV acetaminophen in children with fever and mild to moderate pain. PATIENTS AND METHODS: Total 60 children aged six months to 6 years, with fever and pain, that were treated with rectal or intravenous acetaminophen were selected and assigned in two groups. The IV group received 10mg/kg paracetamol as an IV infusion, and the rectal group received a 15mg/kg dose immediately after admission. Pain score was calculated using the FLACC method, and the axillary temperature was recorded at baseline and then 0.5, 1, 2, 4, and 6hours after drug administration. Blood samples were collected at baseline and then at 30min-intervals for the first 90minutes. RESULTS: The trend of changes in mean pain score at different time intervals was significantly different between the two groups. Body temperature decrease was more prominent in the IV group. The plasma concentration increased in both groups significantly with time. This increase was sharper in the IV group, just in the first 60minutes after drug administration. CONCLUSIONS: IV acetaminophen has more rapid onset of action, while rectal dosage form control fever and pain for longer duration. Considering its favorable effects with ease of administration and lower cost, rectal acetaminophen can be a reasonable option in selected patients with pain or fever.

Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

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.

Kaempferol 3-O-Rutinoside, a Flavone Derived from Tetrastigma hemsleyanum Diels et Gilg, Reduces Body Temperature through Accelerating the Elimination of IL-6 and TNF-α in a Mouse Fever Model.

Fever is a serious condition that can lead to various consequences ranging from prolonged illness to death. Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) has been used for centuries to treat fever, but the specific chemicals responsible for its antipyretic effects are not well understood. This study aimed to isolate and identify the chemicals with antipyretic bioactivity in T. hemsleyanum extracts and to provide an explanation for the use of T. hemsleyanum as a Chinese herbal medicine for fever treatment. Our results demonstrate that kaempferol 3-rutinoside (K3OR) could be successfully isolated and purified from the roots of T. hemsleyanum. Furthermore, K3OR exhibited a significant reduction in rectal temperature in a mouse model of fever. Notably, a 4 µM concentration of K3OR showed more effective antipyretic effects than ibuprofen and acetaminophen. To explore the underlying mechanism, we conducted an RNA sequencing analysis, which revealed that PXN may act as a key regulator in the fever process induced by lipopolysaccharide (LPS). In the mouse model of fever, K3OR significantly promoted the secretion of IL-6 and TNF-α during the early stage in the LPS-treated group. However, during the middle to late stages, K3OR facilitated the elimination of IL-6 and TNF-α in the LPS-treated group. Overall, our study successfully identified the chemicals responsible for the antipyretic bioactivity in T. hemsleyanum extracts, and it answered the question as to why T. hemsleyanum is used as a traditional Chinese herbal medicine for treating fever. These findings contribute to a better understanding of the therapeutic potential of T. hemsleyanum in managing fever, and they provide a basis for further research and development in this field.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

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.

Antipyretic effect of inhaled Tetrastigma hemsleyanum polysaccharide on substance and energy metabolism in yeast-induced pyrexia mice via TLR4/NF-κb signaling pathway.

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.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida.

ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

Antipyretic activity of the hydro-alcoholic extract of Artemisia absinthium L. as a standalone and as an adjuvant with barley water against yeast-induced pyrexia in albino Wistar rats.

OBJECTIVES: In Unani medicine, a comprehensive treatment plan has been delineated to deal with febrile illnesses using herbal drugs along with modified dietetics, which stands as a promising area of research. The present study was aimed at evaluating the antipyretic activity of the HAE of Artemisia absinthium L. whole plant as a standalone and as an adjuvant with barley water in an animal model of pyrexia to validate the age-old Unani principle of the treatment. METHODS: The pyrexia was induced in all the groups except the plain control using Brewer's yeast. Group II did not receive any treatment, while group III received crocin, group IV received HAE of A. absinthium, group V administered Ma al-Sha'ir, and group VI was treated with the HAE of A. absinthium along with Ma al-Sha'ir by oral route. The rectal temperature of each rat was recorded at '0' h, 30 min, 60 min, and 180 min. RESULTS: The mean rectal temperature of group III went down from 101.82±0.20 °F to 100.4±0.57 °F over the period of (0-180) minutes, whereas the mean temperature in group IV went down from 102.45±0.60 °F to 100.14±0.57 °F. The mean rectal temperature of group V decreased from 100.62±0.11 °F to 99.55±0.51 °F, while the mean rectal temperature of group VI went down from 101.95±0.1 °F to 97.7±0.11 °F. CONCLUSIONS: It is concluded that the HAE of A. absinthium L. as a standalone and along with Ma al Sha'ir showed excellent antipyretic activity as compared to the standard drug in an animal model.

Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder.

CONTEXT: Zi Xue Powder (ZXP) is a traditional formula for the treatment of fever. However, the potential mechanism of action of ZXP remains unknown. OBJECTIVE: This study elucidates the antipyretic characteristics of ZXP and the mechanism by which ZXP alleviates fever. MATERIALS AND METHODS: The key targets and underlying fever-reducing mechanisms of ZXP were predicted using network pharmacology and molecular docking. The targets of ZXP anti-fever active ingredient were obtained by searching TCMSP, STITCH and HERB. Moreover, male Sprague-Dawley rats were randomly divided into four groups: control, lipopolysaccharide (LPS), ZXP (0.54, 1.08, 2.16 g/kg), and positive control (acetaminophen, 0.045 g/kg); the fever model was established by intraperitoneal LPS injection. After the fever model was established at 0.5 h, the rats were administered treatment by gavage, and the anal temperature changes of each group were observed over 10 h after treatment. After 10 h, ELISA and Western blot analysis were used to further investigate the mechanism of ZXP. RESULTS: Network pharmacology analysis showed that MAPK was a crucial pathway through which ZXP suppresses fever. The results showed that ZXP (2.16 g/kg) decreased PGE2, CRH, TNF-a, IL-6, and IL-1ß levels while increasing AVP level compared to the LPS group. Furthermore, the intervention of ZXP inhibited the activation of MAPK pathway in LPS-induced fever rats. CONCLUSIONS: This study provides new insights into the mechanism by which ZXP reduces fever and provides important information and new research ideas for the discovery of antipyretic compounds from traditional Chinese medicine.

Temporary impact on medical system and effectiveness of mitigation strategies after COVID-19 policy adjustment in China: a modeling study.

Background: As China amends its "zero COVID" strategy, a sudden increase in the number of infections may overwhelm medical resources and its impact has not been quantified. Specific mitigation strategies are needed to minimize disruption to the healthcare system and to prepare for the next possible epidemic in advance. Method: We develop a stochastic compartmental model to project the burden on the medical system (that is, the number of fever clinic visits and admission beds) of China after adjustment to COVID-19 policy, which considers the epidemiological characteristics of the Omicron variant, age composition of the population, and vaccine effectiveness against infection and severe COVD-19. We also estimate the effect of four-dose vaccinations (heterologous and homologous), antipyretic drug supply, non-pharmacological interventions (NPIs), and triage treatment on mitigating the domestic infection peak. Result: As to the impact on the medical system, this epidemic is projected to result in 398.02 million fever clinic visits and 16.58 million hospitalizations, and the disruption period on the healthcare system is 18 and 30 days, respectively. Antipyretic drug supply and booster vaccination could reduce the burden on emergency visits and hospitalization, respectively, while neither of them could not reduce to the current capacity. The synergy of several different strategies suggests that increasing the heterologous booster vaccination rate for older adult to over 90% is a key measure to alleviate the bed burden for respiratory diseases on the basis of expanded healthcare resource allocation. Conclusion: The Omicron epidemic followed the adjustment to COVID-19 policy overloading many local health systems across the country at the end of 2022. The combined effect of vaccination, antipyretic drug supply, triage treatment, and PHSMs could prevent overwhelming medical resources.

The association between antipyretic analgesics use and SARS-CoV-2 antibody titers following the second dose of the BNT162b2 mRNA vaccine: An observational study.

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.

Surveillance of COVID-19 and influenza A(H1N1) prevalence in China via medicine-based wastewater biomarkers.

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.

Isolation, preparation and investigation of leaf extracts of Aloe barbadensis for its remedial effects on tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) by in vivo and in silico approaches in experimental rats.

Aloe barbadensis is a stemless plant with a length of 60-100 cm with juicy leaves which is used for its remedial and healing properties in different suburbs of various countries. The present study was conducted to investigate the effect of A. barbadensis leaf extract (aqueous and ethanolic) in yeast induced pyrexia and acetic acid induced writhing in rat model to evaluate the antipyretic biomarkers and its phytochemical screening with computational analysis. For analgesic activity model 60 Albino rats (160-200 kg) were divided into four groups. Of the 4 groups, control consisted of 6 rats (Group I) treated with normal saline, standard comprised of 6 rats treated with drug diclofenac (Group I). Experimental groups consisted of 48 rats, treated with A. barbadensis ethanolic and aqueous leaf extracts at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg (Group III. IV). For antipyretic activity group division was same as in analgesic activity. All groups were treated the same as in the analgesic activity except for the second group which was treated with paracetamol. In both antipyretic and analgesic activity at the dose of 400 mg/kg, group III showed significant inhibition. TNF-α and IL-6 showed significant antipyretic activity at a dose of 400 mg/kg. For molecular docking aloe emodin and cholestanol were used as ligand molecules to target proteins Tnf-α and IL-6. Acute oral toxicity study was performed. There was no mortality even at the dose of 2000 mg/kg. Quantitative and qualitative phytochemical screening was performed for the detection of various phytochemicals. Hence, A. barbadensis leaf extracts can be used in the form of medicine for the treatment of pain and fever.

Knowledge, attitudes, and practices toward over-the-counter antipyretics among fever patients: a cross-sectional study in the context of a policy change KAP of OTC antipyretics.

Background: On January 8, 2023, a change in the control policy for COVID-19 was implemented in China, whereby patient self-management of fever typically entails the utilization of over-the-counter fever-reducing medications. Objective: This study aimed to investigate the knowledge, attitudes, and practices (KAP) toward over-the-counter (OTC) antipyretics among fever patients. Methods: This cross-sectional study was conducted between October 2022 and February 2023 at author's hospital in Wuhan, China, among fever patients on OTC antipyretics, using a self-administered questionnaire. Results: A total of 481 valid questionnaires were collected, with the age of 36.05 ± 12.10 years, including 240 (49.90%) males, and 209 (43.45%) collected before policy change. The knowledge, attitudes, precautions for medication administration and decision-making practices scores were 6.86 ± 3.30 (possible range: 0-12), 16.67 ± 2.46 (possible range: 7-35), 29.98 ± 5.41 (possible range: 7-35) and 27.87 ± 1.28 (possible range: 8-40), respectively. The multivariable logistic regression analysis showed that knowledge (OR = 0.83, 95%CI: 0.81-0.92, p < 0.001) was independently associated with positive attitude. Knowledge (OR = 1.41, 95%CI: 1.28-1.56, p < 0.001), attitude (OR = 0.87, 95%CI: 0.79-0.95, p = 0.004), suburban (OR = 0.45, 95%CI: 0.23-0.88, p = 0.019) were independently associated with proactive precautions for medication administration practices. Knowledge (OR = 1.14, 95%CI: 1.07-1.22, p < 0.001), attitude (OR = 0.90, 95%CI: 0.82-0.98, p = 0.018), responding after policy change, 2023 (OR = 1.70, 95%CI: 1.10-2.63, p = 0.016) were independently associated with proactive decision making practices. Conclusion: Fever patients had moderate knowledge, negative attitude, proactive precautions for medication administration practices, moderate decision-making practices. After the policy change, there was a significant increase in knowledge regarding medication administration precautions and decision-making.

[Cost-effectiveness analysis of Chaiyin Granules in treatment of influenza].

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.

Intravenous ibuprofen in postoperative pain and fever management in adults: A systematic review and meta-analysis of randomized controlled trials.

This study aims to evaluate the efficacy and safety of multiple or single-dosage intravenous ibuprofen (IVIB) in managing postoperative pain and fever in adults who are unable to take oral medications. A systematic review and meta-analysis was conducted based on randomized controlled trials (RCTs) comparing IVIB with placebo or other analgesic and antipyretic medications for postoperative pain and fever management. Data were collected from 8 main databases from the inception to June 2022. Risk of bias assessment was performed, and the GRADE methodology was used to assess the certainty of pooled evidence. Primary outcomes included visual analogue scale (VAS) scores within 24 h postoperative and reduction of temperature. Meta-analyses were conducted to calculate the mean difference (MD) or risk ratios (RR) and 95% CIs. As a result, a total of twenty-three RCTs with 3716 participants were included. For postoperative pain, with moderate-to-low certainty evidence, IVIB was associated with lower postoperative VAS scores than placebo, with MD ranging from -3.53 (95% CI, -4.32 to -2.75) at 0 min to -0.96 (95% CI, -1.35 to -0.57) at 24 h. Compared with intravenous acetaminophen, IVIB demonstrated lower VAS scores (MD, -1.54 at 0 min; -0.36 at 24 h). For fever, IVIB showed satisfactory antipyretic efficiency in a short period of time, but no difference was observed between IVIB and intravenous acetaminophen. IVIB was well-tolerated for both pain and fever management. In conclusion, moderate-to-low certainty evidence supports the use of IVIB for adults with postoperative pain and fever who are unable to take oral medications.