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JAMA Neurology Jun 2024A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and...
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.
PubMed: 38857015
DOI: 10.1001/jamaneurol.2024.1677 -
Analytical Methods : Advancing Methods... Jun 2024A facile electrochemical approach is proposed for the synchronous determination of acetaminophen (ACP), codeine (COD) and caffeine (CAF) utilizing unmodified...
A facile electrochemical approach is proposed for the synchronous determination of acetaminophen (ACP), codeine (COD) and caffeine (CAF) utilizing unmodified screen-printed electrodes (SPEs). The determination of ACP, COD and CAF has been explored across different supporting electrolytes including sulfuric acid (HSO), hydrochloric acid (HCl), phosphoric acid (HPO) and Briton Robinson (B.R) buffer solutions. It was found that a 0.05 mol L sulfuric acid solution is an optimal supporting electrolyte utilized for voltammetric analysis of ACP, COD, and CAF with improved sensitivity, stability, and reproducibility. The electro-analytical sensing of ACP, COD and CAF was investigated using SPEs within linear concentration ranges of 3.0-35.0 μmol L, 10-160 μmol L and 10-160 μmol L and revealed competitively low limits of detection (3S/N) of 0.9, 4.8 and 6.3 μmol L for ACP, COD and CAF, respectively. The results indicated the possibility of such a simple and quick electroanalytical protocol for online monitoring of pharmaceutical formulations comprising ACP, COD, and CAF drugs in human fluids with satisfactory recovery.
Topics: Acetaminophen; Codeine; Caffeine; Humans; Graphite; Electrodes; Electrochemical Techniques; Limit of Detection; Reproducibility of Results
PubMed: 38855887
DOI: 10.1039/d4ay00449c -
Theranostics 2024Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene...
Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene expression during murine APAP-induced ALI by 3'mRNA sequencing (massive analysis of cDNA ends, MACE), we observed splenic mRNA accumulation encoding for the neutrophil serine proteases cathepsin G, neutrophil elastase, and proteinase-3 - all are hierarchically activated by cathepsin C (CtsC). This, along with increased serum levels of these proteases in diseased mice, concurs with the established phenomenon of myeloid cell mobilization during APAP intoxication. In order to functionally characterize CtsC in murine APAP-induced ALI, effects of its genetic or pharmacological inhibition were investigated. We report on substantially reduced APAP toxicity in CtsC deficient mice. Alleviation of disease was likewise observed by treating mice with the CtsC inhibitor AZD7986, both in short-term prophylactic and therapeutic protocols. This latter observation indicates a mode of action beyond inhibition of granule-associated serine proteases. Protection in CtsC knockout or AZD7986-treated wildtype mice was unrelated to APAP metabolization but, as revealed by MACE, realtime PCR, or ELISA, associated with impaired expression of inflammatory genes with proven pathogenic roles in ALI. Genes consistently downregulated in protocols tested herein included , , and . Moreover, , a positive regulator of the toll-like receptor/interferon-axis, was reduced by targeting CtsC. This work suggests CtsC as promising therapeutic target for the treatment of ALI, among others paradigmatic APAP-induced ALI. Being also currently evaluated in phase III clinical trials for bronchiectasis, successful application of AZD7986 in experimental APAP intoxication emphasizes the translational potential of this latter therapeutic approach.
Topics: Animals; Acetaminophen; Cathepsin C; Mice; Chemical and Drug Induced Liver Injury; Mice, Inbred C57BL; Mice, Knockout; Male; Disease Models, Animal
PubMed: 38855187
DOI: 10.7150/thno.96092 -
Cureus May 2024Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the...
Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) endorse the use of misoprostol not only for the prevention but also for the treatment of PPH. However, the administration of misoprostol is commonly associated with transient pyrexia, attributed to a shift in the hypothalamic set point observed in certain animal studies. Misoprostol-induced hyperpyrexia can occasionally manifest with a prodrome of shivering, particularly when administered via the sublingual route, which achieves a higher and faster maximum plasma concentration compared to vaginal and rectal routes. General management strategies to reduce fever involve removing clothing and blankets, applying cool compresses, administering oral acetaminophen, and ensuring adequate hydration. While some cases have reported misoprostol-induced convulsions, hyperpyrexia leading to convulsions and subsequent rhabdomyolysis is a rare and potentially lethal side effect. In this case presentation, we emphasize a scenario where misoprostol was employed for the treatment of PPH but led to rhabdomyolysis. Our goal is to highlight the side effects of misoprostol and the significance of considering the initial combination of misoprostol with anti-pyretic management to minimize the risk of hyperthermia-related side effects and prevent additional severe complications.
PubMed: 38854268
DOI: 10.7759/cureus.59874 -
Archives of Dermatological Research Jun 2024Rising melanoma rates have spurred interest in preventive strategies. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, show potential in reducing... (Review)
Review
Rising melanoma rates have spurred interest in preventive strategies. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, show potential in reducing cancer risks. NSAIDs act on cyclooxygenase (COX) enzymes, impacting COX-2 associated with inflammation and cancer progression. This paper explores aspirin's role in cutaneous melanoma prevention, elucidating its mechanisms and acknowledging varying literature outcomes. Rather than providing conclusive recommendations, the review emphasizes the influence of individual factors, contributing to the ongoing dialogue on aspirin's complexities in melanoma prevention. A PubMed search using "Aspirin" AND "Cutaneous melanoma" yielded relevant English-language, peer-reviewed studies. Selection criteria focused exclusively on skin cancers, specifically cutaneous melanoma. Exclusions included studies covering various cancers, some non-dermatologic, and those not evaluating aspirin use independently but in conjunction with NSAIDs. The potential chemopreventive effects of aspirin and NSAIDs against melanoma have gained attention due to their association with a reduced risk of various cancers including gastric, colorectal, and breast. By inhibiting COX enzymes and the NF-κB pathway, these agents theoretically slow malignant cell activities, presenting a prospect for cancer prevention. Aspirin exhibits noteworthy effects, depleting growth-stimulating hormones, generating reactive oxygen species harmful to cancerous cells, and inhibiting COX-2 linked to cancer progression. Limited literature suggests survival benefits with aspirin use in stage II and III melanoma, possibly due to slowing disease progression, evident in smaller Breslow depths. Gender-specific responses to aspirin are notable, with some studies reporting a stronger chemopreventive correlation in females. It's crucial to note that geographic disparities, demographic cohorts, and individual-specific factors are confounding variables that may contribute to conflicting findings regarding aspirin's impact on melanoma. The association between aspirin use and melanoma risk is complex, with conflicting findings across diverse populations. Although it appears that more studies suggest a protective role for aspirin rather than not, evidence lacks consistency. Factors such as gender, geography, race, sun exposure, and health conditions play a role in shaping these varied outcomes, necessitating large-scale, prospective studies research and standardized parameters for more conclusive insights that may help guide tailored clinical strategies for melanoma prevention.
Topics: Humans; Aspirin; Skin Neoplasms; Melanoma; Anti-Inflammatory Agents, Non-Steroidal; Melanoma, Cutaneous Malignant; Female; Male; Cyclooxygenase 2; Chemoprevention
PubMed: 38850411
DOI: 10.1007/s00403-024-03056-3 -
Life Sciences Aug 2024Acetaminophen (APAP), a widely used pain and fever reliever, is a major contributor to drug-induced liver injury, as its toxic metabolites such as NAPQI induce oxidative...
Acetaminophen (APAP), a widely used pain and fever reliever, is a major contributor to drug-induced liver injury, as its toxic metabolites such as NAPQI induce oxidative stress and hepatic necrosis. While N-acetylcysteine serves as the primary treatment for APAP-induced liver injury (AILI), its efficacy is confined to a narrow window of 8-24 h post-APAP overdose. Beyond this window, liver transplantation emerges as the final recourse, prompting ongoing research to pinpoint novel therapeutic targets aimed at enhancing AILI treatment outcomes. Nerve injury-induced protein 1 (Ninjurin1; Ninj1), initially recognized as an adhesion molecule, has been implicated in liver damage stemming from factors like TNFα and ischemia-reperfusion. Nonetheless, its role in oxidative stress-related liver diseases, including AILI, remains unexplored. In this study, we observed up-regulation of Ninj1 expression in the livers of both human DILI patients and the AILI mouse model. Through the utilization of Ninj1 null mice, hepatocyte-specific Ninj1 KO mice, and myeloid-specific Ninj1 KO mice, we unveiled that the loss of Ninj1 in hepatocytes, rather than myeloid cells, exerts alleviative effects on AILI irrespective of sex dependency. Further in vitro experiments demonstrated that Ninj1 deficiency shields hepatocytes from APAP-induced oxidative stress, mitochondrial dysfunctions, and cell death by bolstering NRF2 stability via activation of AMPKα. In summary, our findings imply that Ninj1 likely plays a role in AILI, and its deficiency confers protection against APAP-induced hepatotoxicity through the AMPKα-NRF2 pathway.
Topics: Animals; Acetaminophen; Chemical and Drug Induced Liver Injury; NF-E2-Related Factor 2; Mice; AMP-Activated Protein Kinases; Humans; Male; Mice, Knockout; Cell Adhesion Molecules, Neuronal; Mice, Inbred C57BL; Signal Transduction; Oxidative Stress; Hepatocytes; Liver; Female; Nerve Growth Factors
PubMed: 38848941
DOI: 10.1016/j.lfs.2024.122782 -
BMJ Paediatrics Open Jun 2024Neural tube defects are a significant cause of morbidity and mortality that can occur in the early pregnancy periods. Though the burden is high, it gains only limited...
Determinants of neural tube defect among newborns admitted to neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, Southern Ethiopia: a case-control study.
BACKGROUND
Neural tube defects are a significant cause of morbidity and mortality that can occur in the early pregnancy periods. Though the burden is high, it gains only limited attention. In Ethiopia, the estimated number of neural tube defect cases was significantly higher. So, identifying factors contributing to it would be significant for planning risk reduction and preventive strategies. Therefore, identifying the possible determinants was aimed at this study.
METHODS
A hospital-based, unmatched case-control study was conducted on 104 cases and 208 controls selected from neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, southern Ethiopia from December 2021 to November 2022. All neural tube defect cases were included consecutively and controls were selected by using a simple random sampling method. Data were collected using interviewer-administered semistructured questionnaires. Data analysis was done by using SPSS V.25. Binary logistic regression was used, and variables with a p value less than 0.25 in bivariate analysis were entered into the multivariable logistic regression model. An adjusted OR with a 95% CI was estimated, and finally, variables that show a level of p value less than 0.05 in multivariable analysis were declared statistically significant.
RESULT
After controlling confounders, factors such as unplanned pregnancy 2.20 (95% CI 1.20 to 4.041), history of abortions 2.09 (95% CI 1.19 to 3.67), khat chewing 6.67 (95% CI 2.95 to 15.06), antipyretic and analgesic medications 2.87 (95% CI 1.47 to 5.56) and, being a female neonate 2.11 (95% CI 1.21 to 3.67) were significantly associated with a neural tube defect.
CONCLUSION
This study has identified some determinants of neural tube defects. Hence, the behavioural, medical and obstetrical conditions of mothers need serious evaluation in the prepregnancy period. So, improving preconception counselling and prenatal care practices would have a significant role in reducing the risk of neural tube defects.
Topics: Humans; Ethiopia; Female; Case-Control Studies; Infant, Newborn; Intensive Care Units, Neonatal; Hospitals, Teaching; Male; Pregnancy; Neural Tube Defects; Adult; Risk Factors; Young Adult
PubMed: 38844382
DOI: 10.1136/bmjpo-2023-002235 -
Alternative Therapies in Health and... Jun 2024Diarrheal irritable bowel syndrome is a common functional intestinal disease in gastroenterology that can affect approximately 9% of children worldwide, and more than...
BACKGROUND
Diarrheal irritable bowel syndrome is a common functional intestinal disease in gastroenterology that can affect approximately 9% of children worldwide, and more than half of all affected children have abdominal pain into adulthood. Research has shown that scientific and effective nursing can play an important role in improving the condition and prognosis of diarrheal irritable bowel syndrome in children.
OBJECTIVE
To explore the effect of high-quality nursing intervention on clinical efficacy and prognosis of diarrheal irritable bowel syndrome in children.
DESIGN
This was a retrospective study.
SETTING
This study was performed in the department of Fourth Department of Pediatrics, Ningbo Women & Children's Hospital.
PARTICIPANTS
A total of 60 children with diarrheal irritable bowel syndrome admitted to the Pediatric Gastroenterology Department of our hospital from August 2017 to August 2019 were enrolled.
INTERVENTIONS
At the same time as symptomatic treatment, high-quality nursing intervention was implemented, including cognitive intervention, psychological intervention, dietary guidance, life coaching, and medication guidance.
PRIMARY OUTCOME MEASURES
(1) clinical efficacy (2) clinical symptom points (3) symptom relief time (4) incidence of adverse reactions (5) negative emotions (6) treatment compliance and (7) nursing satisfaction of family members. All theses primary outcome measures could indicate the impacts of high-quality nursing intervention on the overall treatment and prognosis of diarrheal irritable bowel syndrome in children.
RESULTS
The total effective rate was 98.33%. The scores of abdominal distension, abdominal pain, and diarrhea after treatment were significantly lower than those before treatment (P < .05). The anxiety and depression scores of children were lower after treatment than before treatment (P < .05). After treatment, the antipyretic time, antidiarrheal time, and correct dehydration time were (1.44±0.28) d, (1.46±0.33) d and (1.38±0.31) d. The treatment compliance and nursing satisfaction of the family members of the children was 100.00%, and the satisfaction score was 94.60±3.28 points. There were no obvious adverse reactions.
CONCLUSION
High-quality nursing intervention combined with treatment of children with diarrheal irritable bowel syndrome can effectively improve clinical treatment effect, improve clinical symptoms, improve children's negative emotions and promote children's treatment compliance and nursing satisfaction of families, and have no obvious adverse reactions, which is worthy of clinical promotion. Our study provides a clinical reference for the nursing of children with diarrheal irritable bowel syndrome.
PubMed: 38843431
DOI: No ID Found -
Neurosurgical Review Jun 2024Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative...
Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage.
Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33-4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31-6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64-5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB.
Topics: Humans; Male; Female; Aspirin; Aged; Middle Aged; Retrospective Studies; Cerebral Hemorrhage; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Risk Factors; Adult; Intracranial Hemorrhages
PubMed: 38839660
DOI: 10.1007/s10143-024-02481-2