Fixed drug eruptions (FDEs) are dermatological manifestations characterized by recurrent lesions at the same site upon re-exposure to the causative drug. We present a novel case of a 32-year-old female who developed bilateral symmetrical erythematous papules on her thighs following the use of chlorzoxazone for chronic back pain. This case is particularly significant as it underscores the potential for this specific drug, which is commonly prescribed, to induce FDE-a reaction previously unreported in the literature. The findings emphasize the necessity for clinicians to maintain a high index of suspicion for drug-induced skin reactions, even with medications considered safe and routinely used. This case serves as a critical reminder of the importance of thorough medication history assessments and the potential implications of drug interactions in dermatological care.

More than 20 previously reported lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to the aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in silico methods to create an ideal (virtual) population of 120,000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal dataset shows little to no risk of acetaminophen use if the cofactors that create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors that impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in the analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD.

In traditional Chinese medicine, Ganoderma is a kind of edible and medicinal mushroom, which is widely used because of its significant pharmacological activity. There are many species within the Ganoderma genus, each with different material bases and applications. However, detailed studies on these species are still lacking. In this study, we investigated the metabolites of G. leacontextum (B), G. lucidum (C), G. tsugae (S) from Changbai Mountain, and G. tsugae (M) from Mongolia using metabolomics. The PCA results indicated minimal differences between M and S, whereas B and S exhibited significant variations. A total of 708 differential metabolites were identified in this study, with steroids, triterpenoids, phenols, and quinones being the major metabolites. Specifically, triterpenoids and steroids were higher in C. Meanwhile, phenolic compounds were more abundant in B. Additionally, quinones were more abundant in M and S. We validated some of the main compounds, and the results showed that paracetamol was most abundant in B, making paracetamol a potential marker for identifying B. Additionally, vitamin K3 was found to be more abundant in M and S, which can serve as a marker for their identification. This study provides new insights and a theoretical basis for the development and utilization of the genus Ganoderma.

OBJECTIVE: Renal colic (RC) is a common urologic emergency often leading to significant pain and recurrent hospital visits. This study aimed to compare the efficacy and safety of piroxicam versus paracetamol in preventing pain recurrence and hospital readmission in patients treated for RC and discharged from the emergency department (ED).
METHODS: A prospective, randomized, single-blind trial was conducted in four EDs. Eligible adults with RC were randomized to receive oral piroxicam, paracetamol, or placebo for 5 days post-ED discharge. Primary outcomes included pain recurrence and ED readmission within 7 days. Secondary outcomes included time to recurrence and treatment-related side effects.
RESULTS: Of 1383 enrolled patients, no significant differences were observed among the groups regarding baseline characteristics. Pain recurrence rates within 7 days were 29% (95% confidence interval [CI] 24.9%-33.2%) for piroxicam, 30.3% (95% CI 26.1%-34.5%) for paracetamol, and 30.8% (95% CI 26.6%-35.0%) for placebo, with no significant between-group differences (p = 0.84). Among patients experiencing recurrence, the majority encounter it within the initial 2 days following their discharge (86% in the piroxicam group, 84.1% in the paracetamol group, and 86% in the placebo group, respectively). ED readmission rates were similar across groups: 20.8% (95% CI 17.1%-24.5%) in the piroxicam group, 23.8% (95% CI 19.9%-27.7%) in the paracetamol group, and 22.9% (95% CI 19.1%-26.8%) in the placebo group (p = 0.52). The piroxicam group reported significantly higher adverse effects compared to others.
CONCLUSIONS: Piroxicam and paracetamol did not demonstrate efficacy in preventing pain recurrence or ED readmission within the first week following RC treatment.

UNASSIGNED: We explored in mice, the analgesic, tolerance, dependency, and rewarding effects of systemic acetaminophen (APAP).
UNASSIGNED: Studies employed adult mice (C57Bl6). (1) Intraplantar formalin flinching + post formalin allodynia. Mice were given intraperitoneal APAP in a DMSO (5%)/Tween 80 (5%) or a water-based formulation before formalin flinching on day 1 and tactile thresholds assessed before and after APAP at day 12. (2) Paw incision. At 24 hours and 8 days after hind paw incision in male mice, effects of intraperitoneal APAP on tactile allodynia were assessed. (3) Repeated delivery. Mice received daily (4 days) analgesic doses of APAP or vehicle and tested upon formalin flinching on day 5. (4) Conditioned place preference. For 3 consecutive days, vehicle was given in the morning in either of 2 chambers and in each afternoon, an analgesic dose of morphine or APAP in the other chamber. On days 5 and 10, animals were allowed to select a \"preferred\" chamber.
UNASSIGNED: Formalin in male mice resulted in biphasic flinching and an enduring postformalin tactile allodynia. Acetaminophen dose dependently decreased phase 2 flinching, and reversed allodynia was observed postflinching. At a comparable APAP dose, female mice showed similarly reduced phase 2 flinching. Incision allodynia was transiently reversed by APAP. Repeated APAP delivery showed no loss of effect after sequential injections or signs of withdrawal. Morphine, but not APAP or vehicle, resulted in robust place preference.
UNASSIGNED: APAP decreased flinching and allodynia observed following formalin and paw incision and an absence of tolerance, dependence, or rewarding properties.

BACKGROUND: Pyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor.
METHODS: We report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap.
CONCLUSIONS: This case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available.

Angioedema is a non-pitting edema that involves the subcutaneous and submucosal layers of the face, lips, neck, oral cavity, larynx, and gut. It may become life-threatening when it involves tissues of the larynx. Angioedema can be triggered by exposure to drugs such as angiotensin-converting enzyme inhibitors (ACE inhibitors), opioid drugs, and nonsteroidal anti-inflammatory drugs (NSAIDs). Tramadol is an opioid analgesic medication that may also induce angioedema, but the incidence of tramadol-induced angioedema is very rare in literature to date. It has been postulated that tramadol may cause fatal angioedema in the presence of underlying diseases such as systemic lupus erythematosus (SLE) or concomitant drugs such as NSAIDs. We describe the case of a patient with SLE who experienced fatal angioedema following tramadol intake.

UNASSIGNED: Although abdominal pain is one of the major criteria to diagnose acute pancreatitis (AP), there are no standardized guidelines to treat this troublesome symptom in the hospital setting. The aims of the study are to conduct a meta-analysis and to assess the efficacy of nonopioids vs opioids for pain management in AP.
UNASSIGNED: We searched the medical literature through May 2021 to identify randomized controlled trials that examined the efficacy of opioids with nonopioids in AP pain management. Efficacy was reported as odds ratio (OR) with 95% confidence intervals (CIs) of each comparison tested.
UNASSIGNED: We identified 7 eligible randomized controlled trials, containing 389 patients. No significant difference in terms of pain intensity at day 1 (OR 0.82, 95% CI -2.55 to 4.19) was found between opioids and nonopioids. Nonopioids have a significantly high risk of supplementary analgesic use compared with opioids (OR 3.87, 95% CI 1.25-12.04). However, this significance is not seen when comparing nonsteroidal anti-inflammatory drugs and paracetamol with opioids (OR 1.67, 95% CI 0.73-3.82) after excluding trials with procaine. Opioids did not show a significant increase in the complications of pancreatitis, nausea and vomiting, sedation, and deaths when compared with nonopioids.
UNASSIGNED: We found nonopioids, especially nonsteroidal anti-inflammatory drugs and paracetamol, can provide adequate pain relief in patients with AP with no change in supplementary analgesic use and adverse events when compared with opioids. Further research is needed to optimize the use of nonopioids along or in combination with opioids for better pain control in patients with AP.

Metal-organic frameworks (MOFs) with their exceptional properties have the potential to revolutionize the field of electrochemistry and pave the way for new and exciting applications. MOFs is an excellent choice as an active electrocatalyst component in the fabrication of electrochemical sensors. Here, bimetallic NiCo-MOFs, monometallic Ni-MOFs, and Co-MOFs were fabricated to modify the carbon paste electrode. Moreover, the ratio between Co and Ni within the bimetallic MOFs was optimized. Our aim in this work is to synthesize different compositions from bimetallic MOFs and systematically compare their catalytic activity with mono-metallic MOFs on paracetamol. The structure and properties of the 2D NiCo-MOFs were characterized by scanning electron microscope, X-ray photoelectron spectroscopy, Fourier transform infrared, and electrochemical method. Bimetallic Ni0.75Co0.25-MOFs modified carbon paste sensor displayed the optimum sensing performance for the electrochemical detection of paracetamol. A linear response over the range 6.00 × 10- 7 to 1.00 × 10- 4 M with a detection limit of 2.10 × 10- 8 M was obtained. The proposed method was applied to detect paracetamol in spiked human plasma and to determine paracetamol in the presence of its major toxic impurity, p-aminophenol. These findings suggest the considerable potential use of the newly developed sensor as a point-of-care tool for detecting paracetamol and p-aminophenol in the future.

Background and aims Laryngoscopy and intubation cause an increased sympatho-adrenergic pressor response, which can be detrimental to patients with coronary artery disease, hypertension, etc. Various drugs and manoeuvres have been tried to reduce the pressor response with acceptable results but the quest for the ideal drug still continues. Hence, we planned to compare the effects of magnesium sulfate with paracetamol and fentanyl with lignocaine on attenuating the hemodynamic responses due to direct laryngoscopy and intubation and to note the complications of these drugs. Methods We studied 60 adult patients of the American Society of Anaesthesiologists (ASA) physical status I and II of either sex, scheduled for elective surgery under general anaesthesia. The patients were randomly divided into two groups. Group A received 25 mg/kg magnesium sulphate mixed with paracetamol 1 gram IV (100 ml) given over 10 minutes before induction and Group B received 2 mcg/kg fentanyl and 1.5 mg/kg lignocaine, 3 minutes before intubation. All patients were uniformly pre-medicated, induced, and intubated as per standard protocol. Heart rate (HR) and systemic arterial pressures were recorded at baseline, after study drug infusion, after induction, and 1, 3, 5, 10, and 15 mins after intubation. Hemodynamic parameters were compared using repeated measures analysis of variance (ANOVA). In the post-hoc tests, p value < 0.05 was considered statistically significant. Results We observed the mean pre-op HR (p = 0.161) and mean HR one-minute post-induction (p = 0.144). The percentage change from baseline at one-minute post-induction was 9.7 in Group A and 15.2 in Group B. We observed the mean pre-op mean arterial pressure (MAP) (p = 0.119) and mean MAP one minute post-induction (p = 0.585). The percentage change from baseline at one-minute post-induction was 3.3 in Group A and 2.8 in Group B. The percentage change from baseline was found to be within 15%, for HR in Group A and for systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP in Group B. However, there was no statistically significant difference (p > 0.05) between the mean HR, SBP, DBP, and MAP between the time points. Conclusion In our study, both the combinations of drugs, magnesium sulphate with paracetamol (Group A drugs) and fentanyl with lignocaine (Group B drugs) were found to be equally effective (i.e. neither group was superior to the other) in attenuating the hemodynamic response to laryngoscopy and intubation.