[Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase â ¡b clinical trial].

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

Does the use of antipyretics prolong illness? A systematic review of the literature and meta-analysis on the effects of antipyretics in acute upper and lower respiratory tract infections.

OBJECTIVE: Fever contributes to the inflammatory response; in some infections, antipyretics could prolong the illness. The objective of our study was to evaluate the impact of antipyretic treatments on the evolution of acute upper and lower respiratory tract infections (RTI). METHOD: A systematic literature review of randomized controlled trials (RCTs) with meta-analysis was conducted. Our primary endpoint was the time to recovery from illness. Our prespecified secondary endpoints were quality of life, duration and number of fever episodes, repeated medical visits, and adverse events. RESULTS: Out of the 1466 references found, 25 RCTs were included. There were two studies assessing mean fever clearance time, and five studies examining the duration of symptoms associated with the illness studied. No statistically significant differences were found when pooling the results of the different studies. The assessment of adverse events showed a significant difference disadvantaging non-steroidal anti-inflammatory drugs. No meta-analysis could be performed for our other secondary endpoints. The quality of the evidence is limited by the small number of studies included for our primary endpoint and by heterogeneity between the studies. CONCLUSION: Our results suggest that the use of antipyretics does not prolong or shorten illness duration in acute upper and lower RTI. The symptomatic efficacy of antipyretics must be weighed against their adverse effects, particularly when fever is well-tolerated.

Transgenic Zebrafish Expressing Rat Cytochrome P450 2E1 (CYP2E1): Augmentation of Acetaminophen-Induced Toxicity in the Liver and Retina.

Metabolic activation is the primary cause of chemical toxicity including hepatotoxicity. Cytochrome P450 2E (CYP2E) is involved in this process for many hepatotoxicants, including acetaminophen (APAP), one of the most common analgesics and antipyretics. Although the zebrafish is now used as a model for toxicology and toxicity tests, the CYP2E homologue in zebrafish has not been identified yet. In this study, we prepared transgenic zebrafish embryos/larvae expressing rat CYP2E1 and enhanced green fluorescent protein (EGFP) using a ß-actin promoter. Rat CYP2E1 activity was confirmed by the fluorescence of 7-hydroxycoumarin (7-HC), a metabolite of 7-methoxycoumarin that was specific for CYP2 in transgenic larvae with EGFP fluorescence (EGFP [+]) but not in transgenic larvae without EGFP fluorescence (EGFP [-]). APAP (2.5 mM) caused reduction in the size of the retina in EGFP [+] larvae but not in EGFP [-] larvae, while APAP similarly reduced pigmentation in both larvae. APAP at even 1 mM reduced the liver size in EGFP [+] larvae but not in EGFP [-] larvae. APAP-induced reduction of liver size was inhibited by N-acetylcysteine. These results suggest that rat CYP2E1 is involved in some APAP-induced toxicological endpoints in the retina and liver but not in melanogenesis of the developing zebrafish.

[Preparation of salvianolic acid B, tanshinone â ¡_A, and glycyrrhetinic acid lipid emulsion and its protective effect against acute liver injury induced by acetaminophen].

Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.

First-in-human study to evaluate the safety, tolerability and pharmacokinetics of a novel analgesic and antipyretic drug with structural similarity to acetaminophen.

JNJ-10450232 (NTM-006) is a new molecular entity that comprises structural similarities to acetaminophen and provides comparable analgesia in animals and humans without causing the hepatotoxicity associated with acetaminophen overdose in preclinical models. This double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of JNJ-10450232 (NTM-006) following single (50-6000 mg) and multiple (250-2500 mg twice daily for 8 days) doses in healthy male volunteers. JNJ-10450232 (NTM-006) was absorbed within 1-3 h, except at high doses at which Cmax was delayed and bimodal, while increases in AUC were more than dose proportional. CL/F and Vd/F decreased approximately 3-fold with increasing single doses up to 6000 mg and multiple doses up to 1000 mg, resulting in similar t½ values that ranged from 8 to 10 h across doses. JNJ-10450232 (NTM-006) was generally safe and well tolerated, and no dose-limiting toxicities were observed. Transient increases in indirect bilirubin were noted at post-baseline timepoints due to UGT1A1 inhibition, without any evidence of adverse hepatic effects. Macular rash and generalized erythema were the most common drug-related adverse events after multiple doses.

Fever following Covid-19 vaccination in subjects with Brugada syndrome: Incidence and management.

BACKGROUND: Fever is a potential side effect of the Covid-19 vaccination. Patients with Brugada syndrome (BrS) have an increased risk of life-threatening arrhythmias when experiencing fever. Prompt treatment with antipyretic drugs is suggested in these patients. AIM OF THE STUDY: To evaluate the incidence and management of fever within 48 h from Covid-19 vaccination among BrS patients. METHODS: One hundred sixty-three consecutive patients were enrolled in a prospective registry involving five European hospitals with a dedicated inherited disease ambulatory. RESULTS: The mean age was 50 ± 14 years and 121 (75%) patients were male. Prevalence of Brugada electrocardiogram (ECG) pattern type-1, -2, and -3 was 32%, 44%, and 24%, respectively. Twenty-eight (17%) patients had an implantable cardioverter-defibrillator (ICD). Fever occurred in 32 (19%) BrS patients after 16 ± 10 h from vaccination, with a peak of body temperature of 37.9° ± 0.5°. Patients with fever were younger (39 ± 13 vs. 48 ± 13 years, p = .04). No additional differences in terms of sex and cardiovascular risk factors were found between patients with fever and not. Twenty-seven (84%) out of 32 patients experienced mild fever and five (16%) moderate fever. Pharmacological treatment with antipyretic drugs was required in 18 (56%) out of 32 patients and was associated with the resolution of symptoms. No patient required hospital admission and no arrhythmic episode was recorded in patients with ICD within 48 h after vaccination. No induced type 1 BrS ECG pattern and new ECG features were found among patients with moderate fever. CONCLUSION: Fever is a common side effect in BrS patients after the Covid-19 vaccination. Careful evaluation of body temperature and prompt treatment with antipyretic drugs may be needed.

The effectiveness and safety of Chaiqin Qingning Capsule in upper respiratory tract infections with fever: A prospective, double-blinded, randomized, multicenter controlled trial.

BACKGROUND AND AIM: Presently, over-the-counter drugs that can treat upper respiratory tract infections (URTI) are rarely effective and safe. Chaiqin Qingning Capsule (CQQNC), a Chinese patent medicine, which has been verified by long-term clinical practice is recommended by Chinese experts for the treatment of URTI with fever. This study conducted a prospective, double-blinded, randomized, multicenter controlled trial to evaluate the effectiveness and safety of CQQNC in the treatment of URTI. METHODS: The study was conducted at 4 clinical centers in China. Eligible subjects were recruited and randomized 1:1 to the CQQNC group and Qingkailing Capsule (QKLC) group. Both groups were administered orally three times a day for three consecutive days. Primary outcomes were the antipyretic onset time and the temperature recovery time. Secondary outcomes included the symptom disappearance rate, symptom score, and drug safety assessment. RESULTS: A total of 269 subjects were analyzed (134 subjects in the CQQNC group, 135 subjects in the QKLC group). The antipyretic onset time and the temperature recovery time were significantly shortened in the CQQNC group (median: 5 h vs. 10 h, p < 0.0001, median: 19 h vs. 27 h, p < 0.0001). CQQNC was more effective than the QKLC in improving the symptoms of pharyngodynia and rhinobyon (85.07% vs. 71.11%, p = 0.008; 76.99% vs. 64.41%, p = 0.043), and in improving the overall symptom scores (-15.10 ± 3.23 vs. -13.35 ± 3.58, p < 0.0001). During the trial, no serious adverse events were reported in the two groups. CONCLUSION: CQQNC is effective and safe in the treatment of URTI with fever, and worthy of clinical application. (http://www.chictr.org.cn, ChiCTR-IPR-16009049).

Reacción adversa a paracetamol en lactante de 2 meses: importancia de los factores coadyuvantes / Adverse reaction to paracetamol in a 2-month-old infant: importance of contributing factors

La intoxicación por paracetamol es la principal causa de intoxicación farmacológica en Pediatría. Aunque en el grupo de lactantes es menos frecuente, los menores de 2 meses presentan particularidades metabólicas que predisponen a la intoxicación por este fármaco. Presentamos el caso de una lactante de 2 meses con daño hepático secundario a intoxicación por paracetamol tras administración de una dosis terapéutica del mismo (AU)

Paracetamol toxicity is the main cause of drug poisoning in children. Although less frequent in infants, those younger than 2 months, have metabolic peculiarities that predispose them to intoxication by this drug. Here we present the case of a 2-month-old infant with liver damage secondary to paracetamol intoxication when administering therapeutic doses. (AU)

Investigations of the antipyretic effect and safety of Prasachandaeng, a traditional remedy from Thailand national list of essential medicines.

Prasachandaeng (PSD) remedy from the Thailand National List of Essential Medicines (NLEM) has been used as an antipyretic for chronic fever in both adults and children for centuries. Its therapeutic effect in treating fever and its safety have not been studied in animal models. We evaluated its antipyretic activity on lipopolysaccharide (LPS)-induced fever and safety in the liver in comparison with acetaminophen (ACP). Correlation between biochemistry of liver function and the level of cytochrome P450 (CYP2E1) was also evaluated using an ELISA kit. All doses of PSD powder (PSDP) and a 95% ethanol extract of PSD (PSDE) (50, 200, and 400 mg/kg) showed a significant antipyretic effect (* p < 0.05) as compared to ACP. We investigated clinical biochemistry of liver and kidney functions, histopathology, and concentrations of CYP2E1. All treatment groups demonstrated a normal range of clinical biochemistry of liver and kidney functions in comparison with ACP on days 1, 3, 7, and 10. Serum AST, ALP, and LDH levels of PSDE and PSDP showed mean values less than that of ACP on the corresponding days (* p < 0.05). None of the treatment groups showed evidence of hepatocellular damage, nor did they affect CYPE21. The results of histopathology on liver tissue correlated with the biochemistry of liver functions which indicated no hepatotoxicity effect in liver tissue during the seven day treatment. These findings suggest that both forms of PSD remedy possessed marked antipyretic activity and were not hepatotoxic during the seven days of administration in rats.

Prophylactic drug management for febrile seizures in children.

BACKGROUND: Febrile seizures occurring in a child older than one month during an episode of fever affect 2-4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects of continuous antiepileptic drugs. This is an updated version of a Cochrane Review previously published in 2017. OBJECTIVES: To evaluate primarily the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with febrile seizures; and also to evaluate any other drug intervention where there is a sound biological rationale for its use. SEARCH METHODS: For the latest update we searched the following databases on 3 February 2020: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 31 January 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including the Cochrane Epilepsy Group. We imposed no language restrictions and contacted researchers to identify continuing or unpublished studies. SELECTION CRITERIA: Trials using randomised or quasi-randomised participant allocation that compared the use of antiepileptics, antipyretics or recognised Central Nervous System active agents with each other, placebo, or no treatment. DATA COLLECTION AND ANALYSIS: For the original review, two review authors independently applied predefined criteria to select trials for inclusion and extracted the predefined relevant data, recording methods for randomisation, blinding, and exclusions. For the 2016 update, a third review author checked all original inclusions, data analyses, and updated the search. For the 2020 update, one review author updated the search and performed the data analysis following a peer-review process with the original review authors. We assessed seizure recurrence at 6, 12, 18, 24, 36, 48 months, and where data were available at age 5 to 6 years along with recorded adverse effects. We evaluated the presence of publication bias using funnel plots. MAIN RESULTS: We included 42 articles describing 32 randomised trials, with 4431 randomised participants used in the analysis of this review. We analysed 15 interventions of continuous or intermittent prophylaxis and their control treatments. Methodological quality was moderate to poor in most studies. We found no significant benefit for intermittent phenobarbital, phenytoin, valproate, pyridoxine, ibuprofen, or zinc sulfate versus placebo or no treatment; nor for diclofenac versus placebo followed by ibuprofen, paracetamol, or placebo; nor for continuous phenobarbital versus diazepam, intermittent rectal diazepam versus intermittent valproate, or oral diazepam versus clobazam. There was a significant reduction of recurrent febrile seizures with intermittent diazepam versus placebo or no treatment at six months (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.48 to 0.85; 6 studies, 1151 participants; moderate-certainty evidence), 12 months (RR 0.69, 95% CI 0.56 to 0.84; 8 studies, 1416 participants; moderate-certainty evidence), 18 months (RR 0.37, 95% CI 0.23 to 0.60; 1 study, 289 participants; low-certainty evidence), 24 months (RR 0.73, 95% CI 0.56 to 0.95; 4 studies, 739 participants; high-certainty evidence), 36 months (RR 0.58, 95% CI 0.40 to 0.85; 1 study, 139 participants; low-certainty evidence), 48 months (RR 0.36, 95% CI 0.15 to 0.89; 1 study, 110 participants; moderate-certainty evidence), with no benefit at 60 to 72 months (RR 0.08, 95% CI 0.00 to 1.31; 1 study, 60 participants; very low-certainty evidence). Phenobarbital versus placebo or no treatment reduced seizures at six months (RR 0.59, 95% CI 0.42 to 0.83; 6 studies, 833 participants; moderate-certainty evidence), 12 months (RR 0.54, 95% CI 0.42 to 0.70; 7 studies, 807 participants; low-certainty evidence), and 24 months (RR 0.69, 95% CI 0.53 to 0.89; 3 studies, 533 participants; moderate-certainty evidence), but not at 18 months (RR 0.77, 95% CI 0.56 to 1.05; 2 studies, 264 participants) or 60 to 72 months follow-up (RR 1.50, 95% CI 0.61 to 3.69; 1 study, 60 participants; very low-certainty evidence). Intermittent clobazam compared to placebo at six months resulted in a RR of 0.36 (95% CI 0.20 to 0.64; 1 study, 60 participants; low-certainty evidence), an effect found against an extremely high (83.3%) recurrence rate in the controls, a result that needs replication. When compared to intermittent diazepam, intermittent oral melatonin did not significantly reduce seizures at six months (RR 0.45, 95% CI 0.18 to 1.15; 1 study, 60 participants; very-low certainty evidence). When compared to placebo, intermittent oral levetiracetam significantly reduced recurrent seizures at 12 months (RR 0.27, 95% CI 0.15 to 0.52; 1 study, 115 participants; very low-certainty evidence). The recording of adverse effects was variable. Two studies reported lower comprehension scores in phenobarbital-treated children. Adverse effects were recorded in up to 30% of children in the phenobarbital-treated groups and 36% in benzodiazepine-treated groups. We found evidence of publication bias in the meta-analyses of comparisons for phenobarbital versus placebo (seven studies) at 12 months but not at six months (six studies); and valproate versus placebo (four studies) at 12 months. There were too few studies to identify publication bias for the other comparisons. The methodological quality of most of the included studies was low or very low. Methods of randomisation and allocation concealment often did not meet current standards, and 'treatment versus no treatment' was more commonly seen than 'treatment versus placebo', leading to obvious risks of bias.  AUTHORS' CONCLUSIONS: We found reduced recurrence rates for intermittent diazepam and continuous phenobarbital, with adverse effects in up to 30% of children. The apparent benefit for clobazam treatment in one trial needs to be replicated. Levetiracetam also shows benefit with a good safety profile; however, further study is required. Given the benign nature of recurrent febrile seizures, and the high prevalence of adverse effects of these drugs, parents and families should be supported with adequate contact details of medical services and information on recurrence, first aid management, and, most importantly, the benign nature of the phenomenon.

Síndrome DRESS por paracetamol / DRESS syndrome due to acetaminophen

A síndrome DRESS é uma entidade rara e distinta, caracterizada por acometimento cutâneo e envolvimento de órgãos internos, com risco potencial de morte. O diagnóstico e o tratamento pre- coces são de vital importância. Relatos de DRESS por paraceta- mol são raros na literatura, razão pela qual apresentamos este caso. Paciente do sexo masculino, 56 anos, com surgimento de rash maculopapular, febre, linfadenopatia e hipereosinofilia 3 semanas após suspensão de paracetamol, associados ao ante- cedente familiar de reação a fármaco. Evoluiu bem após pulso- terapia com metilprednisolona.

DRESS syndrome is a rare and distinct entity characterized by cutaneous manifestations and internal organs involvement with a potential risk of death. Early diagnosis and treatment are vi- tally important. Reported cases of DRESS syndrome due to ace- taminophen are rare in the literature, and that is the reason for this case report. A 56-year-old male patient with maculopapular rash, fever, lymphadenopathy, and hypereosinophilia three we- eks after suspension of acetaminophen, associated with a family history of drug reaction. It progressed well after pulse therapy with methylprednisolone.

Flucloxacillin and paracetamol induced pyroglutamic acidosis.

A 75-year-old woman was admitted to a regional hospital with an acute kidney injury (AKI) and nausea on a background of recent treatment for Staphylococcus aureus bacteraemia secondary to pneumonia. The treatment thereof resulted in a high anion gap metabolic acidosis (HAGMA). The pneumonia was initially treated with intravenous piperacillin and tazobactam and the patient transferred to a tertiary hospital. There, the diagnosis of S. aureus bacteraemia secondary to a pulmonary source was confirmed and treatment was changed to intravenous flucloxacillin and the patient was discharged to hospital in the home (HITH is a service that allows short-term healthcare at home to be provided to people who would otherwise need to be in hospital) to complete the antibiotic course. Five weeks after commencing flucloxacillin, the patient was referred back to hospital with nausea and worsening kidney function with an associated significant HAGMA. The patient has a background of chronic kidney disease and chronic back pain for which she was taking long-term paracetamol. The HAGMA was determined to be due to a pyroglutamic acidosis (PGA), deemed secondary to the combined use of paracetamol and flucloxacillin. This was subsequently confirmed with a plasma pyroglutamic acid concentration level of 7467 µmol/L (reference range 20-50 µmol/L) and a urinary level of 1700 mmol/mol creatinine (<110 mmol/mol creatinine). To our knowledge, this is the highest plasma and urinary levels published to date. Furthermore, considering the common use of paracetamol and penicillins, it is important to recognise HAGMA as a potential complication of co-administration of paracetamol and iso-oxylopenicillin. The HAGMA resolved after cessation of flucloxacillin despite the continuation of paracetamol and without administration of N-acetylcysteine. PGA-related HAGMA appears to be a unique potential side effect of iso-oxylopenicillin rather than other beta-lactams.

REPORT- Varying pattern of blood gases, ferritin, procalcitonin, C-Reactive protein, interleukin 6 and lactate dehydrogenase in Covid-19 patients suffering from diverse Co-Morbid, suspected cytokine storm and periodic effects of antiviral and steroidal treatments.

This study depicted varying pattern of inflammatory markers and blood gases of selected SARS Covid-19 patients with triggered cytokine storm, during their stay in ICUs, HDUs, on ventilators for 21 days. All were treated with Antiviral (remdesivir), steroid (dexamethason) and antipyretic (paracetamol) medications. Procalcitonin, PCT, C-reactive protein CRP, Interleukin 6 (IL6) and Lactate dehydrogenase (LDH) blood gases pressure (pO2, pCO2), coagulation (D-Dimer DD) and Iron storage proteins (Ferritin Ft) were analyzed by fully automated analyzers. All biomarkers of each patient category was statistically compared with days 1st, 4th, 7th versus 10th, 14th and 17th days and reported as significant where p<0.05, to assess progression, worsening or recovery status. IL6 (P<0.0224, P< 0.0228) and CRP (P<0.0277) exhibited none or mild statistical significance difference, with the exception of Ferritin (P<0.0185; P<0.0088) and D Dimer (P<0.0086), demonstrating slow recovery, revealing stronger cytokine storming assault. LDH, pCO2 and pO2 exhibited variable significance difference when data of earlier days were compared with recovery phase, thus advocating blended treatment or progressing of disease. Analysis confirms overwhelming pathogenesis of SARS Covid-19 distinctive cytokine storm, which needed to be cautiously monitored as infection progressed using pro-inflammatory biomarkers as indicators of recovery or worsening of the disease.

Paediatric Agranulocytosis Associated with Metamizole Treatment.

PURPOSE: Metamizole, which has antipyretic and pain-relieving properties, is generally used to treat fever in children who do not respond to paracetamol treatment. The most remarkable side effect of metamizole is that it causes myelotoxicity independently of dose. In this study, we aimed to present the clinical features of paediatric patients who developed agranulocytosis after the use of metamizole and draw attention to this side effect. METHODS: The patients who were admitted to Eskisehir Osmangazi University Faculty of Medicine Hospital, Pediatric Infectious Diseases and Pediatric Hematology Service, between January 1, 2015, and December 31, 2018, with a diagnosis of secondary agranulocytosis to metamizole use were examined retrospectively. RESULTS: In all, 12 patients were included in the study; oral metamizole was used in these patients for fever reduction. The mean absolute neutrophil count was 225/mm3 ± 226 (0-600/mm3) at admission, and the neutrophil value of 11 patients was < 500/mm3. The mean length of hospitalisation of the patients was 9.92 ± 8 (3-28) days. Eight patients received intravenous antibiotic therapy and four patients received at least one of the following treatments: intravenous immunoglobulin, granulocyte colony-stimulating factor and methylprednisolone. Bone marrow aspiration examination showed neutrophil/band maturation delaying in the myeloid series with normocellular bone marrow in three patients. Hypocellularity in the bone marrow and decrease in myeloid precursors were observed in three patients. There were no fatal cases. CONCLUSION: The development of agranulocytosis after the use of metamizole causes long-term hospitalisation and may require the use of medications in treatment management. Considering the availability of alternative options to treat fever and pain, and given the side-effect profile of metamizole, it should not be the preferred, first-line antipyretic treatment in children.

Ibuprofen versus paracetamol for treating fever in preschool children in Nigeria: a randomized clinical trial of effectiveness and safety.

INTRODUCTION: fever is the primary symptom of most childhood illnesses and a cause of concern to their caregivers. The antipyretics commonly used to treat fever are ibuprofen and paracetamol. Most studies on the effectiveness of ibuprofen and paracetamol in treating fever in under-fives were conducted in Europe and North America with very few in African children. This study was aimed at assessing the effectiveness and safety of a single dose therapy of ibuprofen versus paracetamol for treating childhood fever in Nigeria. METHODS: a randomized, controlled clinical trial was conducted in the University of Calabar Teaching Hospital, in Nigeria. A total of 140 eligible children aged 6-59 months with tympanic temperature of 38°C-40°C were enrolled, and 70 of them were assigned to one arm that received a single dose of ibuprofen (10mg/kg) and 70 had paracetamol (15mg/kg). After drug administration, the children were admitted and observed in the hospital for six hours during which period a half-hourly temperature measurement and monitoring for adverse events were done. RESULTS: the overall result showed that ibuprofen had a better fever reducing effect compared to paracetamol. The proportion of afebrile children in the ibuprofen versus paracetamol group at 1.5-2.5 hours of administration of the drugs was statistically significant (p = 0.04). The adverse events of both drugs were mild and quite comparable with vomiting being the commonest. CONCLUSION: ibuprofen is more effective in the treating fever in under-fives compared to paracetamol. The adverse events of both drugs were mild and comparable.

[Benefits and risks of ibuprofen in children with fever: Overview of the literature with a view to producing a written information tool for parents]. / Bénéfices et risques de l'ibuprofène chez les enfants fébriles : revue systématique de la littérature en vue de la réalisation d'un outil écrit d'information à destination des patients.

Drug information, as it appears in package leaflet, lacks relevant encrypted data for the patient. The aim of our research was to propose a written model of drug information inspired from the concept of the "Drug Facts Box", about ibuprofen in children with fever. To this end, we carried out a systematic review of systematic literature reviews ("overview") to look for data on the benefits and risks of ibuprofen compared to placebo, paracetamol or a treatment alternating or combining paracetamol and ibuprofen in children with fever aged 0-18 years. 9 systematic reviews were included from the Pubmed/Medline, Embase and Cochrane databases. 1 clinical practice guideline and 2 documents published by the French Haute Autorité de santé (HAS) and the French Agence nationale de sécurité du médicament et des produits de santé (ANSM) were also included. Paracetamol and ibuprofen have a comparable efficacy and safety profile in children with fever. A low increased risk of adverse reactions to ibuprofen is to be feared in specifics clinical situations (chicken pox, pneumonia, angina). Treatments alternating or combining paracetamol and ibuprofen can further lower the temperature compared to paracetamol or ibuprofen alone, but there is no evidence of improved child comfort. The limited data available on the adverse effects of these treatment regimens suggests that they should not be routinely recommended. There is little evidence of the comfort of the febrile child even though it is the primary objective of antipyretic treatment.

The Association Between Concurrence of Infection and the Onset of Severe Eruption or Liver Injury in Patients Using Antipyretic Analgesics: A Matched, Nested Case-Control Study.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) or drug-induced liver injury (DILI) are severe drug-induced reactions, known as idiosyncratic drug reactions. It is believed that immune response can lead to these severe adverse drug reactions. Our previous analysis of the Japanese Spontaneous Drug Reaction database suggested that the onset of SJS/TEN and DILI was strongly associated with infection. Hence, we conducted a matched, nested case-control study to elucidate the association between concurrent infection and the onset of SJS/TEN or liver injury in patients prescribed antipyretic analgesics. We extracted 4 112 055 patients who were prescribed antipyretic analgesics between January 2014 and December 2015. Amongst them, 553 (0.01%) were diagnosed with SJS/TEN and 12 606 (0.3%) with liver injury. In a matched, nested case-control study, 131 and 2847 cases matched for SJS/TEN or liver injury, respectively. For each case, 3 controls were randomly matched with the case for age at index date and sex. In the conditional logistic regression analysis, there was a significant association between the combination of infection and antipyretic analgesics and the onset of SJS/TEN or liver injury (SJS/TEN: adjusted OR, 5.59; 95%CI, 2.01-15.51; liver injury: adjusted OR, 2.79; 95%CI, 2.24-3.46). Although it was not possible to distinguish whether the associations were caused by the infection or were a direct consequence of the antibiotic agents, our findings may help to increase awareness of the possibility of the increased onset of idiosyncratic drug reactions (SJS/TEN and liver injury) in antipyretic analgesic users because of infections.