This study examined the effect of acute acetaminophen (ACTP) ingestion on physical performance during the 5 m shuttle run test (5mSRT), attention, mood states, and the perception of perceived exertion (RPE), pain (PP), recovery (PRS), and delayed onset of muscle soreness (DOMS) in well-trained female athletes. In a randomized, placebo-controlled, double-blind, crossover trial, fifteen well-trained female athletes (age 21 ± 2 years, height 165 ± 6 cm, body mass 62 ± 5 kg) swallowed either 1.5 g of ACTP or 1.5 g of placebo. The profile of mood states (POMS) and digit cancellation (DCT) were assessed 45 min postingestion, and 5mSRT was performed 60 min postingestion. The RPE and PP were determined immediately after each 30-s repetition of the 5mSRT, and the PRS and DOMS were recorded at 5 min and 24 h post-5mSRT. For the 5mSRT, ACTP ingestion improved the greatest distance (+ 10.88%, p < 0.001), total distance (+ 11.33%, p = 0.0007) and fatigue index (+ 21.43%, p = 0.0003) compared to PLA. Likewise, the DCT score was better on the ACTP (p = 0.0007) than on the PLA. RPE, PP, PRS, and DOMS scores were improved after ACTP ingestion (p < 0.01 for all comparisons) compared to PLA. POMS scores were enhanced with ACTP ingestion compared to PLA (p < 0.01). In conclusion, this study indicates that acute acetaminophen ingestion can improve repeated high intensity short-term maximal performance, attention, mood states, and perceptions of exertion, pain, recovery, and muscle soreness in well-trained female athletes, suggesting potential benefits for their overall athletic performance and mood state.

Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and 14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and 14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14) (p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.

This study aims to develop a suitable electrochemical electrode through the incorporation of potassium montmorillonite (MMTK10)clay into the carbon matrix for the direct and sensitive determination of paracetamol (PAR) in pharmaceutical formulations. Electrochemical characterization of the electrodes involves the use of techniques such as cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). The results reveal that the voltammetric response of PAR is linear over a wide concentration range (1.0-15 μM), with a low detection limit of 0.46 μM. Analytically, PAR recovery results were around 94%, indicating that the developed electrode is highly suitable for PAR detection in pharmaceutical formulation. Additionally, density functional theory (DFT) is employed to investigate the reactivity of PAR and explain the interaction process of PAR on the electrode surface at different pH values. A Monte Carlo simulations model is developed to provide a deeper understanding of the adsorption mechanism, particularly to comprehend molecular interactions and preferential orientations of PAR with MMT fractions at the electrode surface. Reduced Density Gradient is calculated and discussed using techniques such as Multiwfn and Visualization of Molecular Dynamics. The developed CPE-MMTK10 sensor provided a simple preparation method, rapid response, high sensitivity, reproducibility, strong selectivity, and extended stability. Moreover, there is a good correlation between most parameters calculated by DFT and experimental results, thereby reinforcing the validity of the theoretical approach in this study.

OBJECTIVE: To investigate whether maternal paracetamol use in early pregnancy is associated with cerebral palsy (CP) in offspring.
METHODS: We conducted a registry and biobank-based case-control study with mother-child pairs. We identified CP cases (n = 322) born between 1995 and 2014 from a nationwide CP-registry. Randomly selected controls (n = 343) and extra preterm controls (n = 258) were obtained from a birth registry. For each mother, a single serum sample from early pregnancy (gestation weeks 10-14) was retrieved from a biobank and analyzed for serum concentrations of paracetamol, categorized into unexposed (<1 ng/ml), mildly exposed (1-100 ng/ml), and highly exposed (>100 ng/ml), and in quartiles. Analyses were performed using logistic regression and adjusted for potential confounders. Separate analyses were conducted including only those children born preterm and only those born term.
RESULTS: Of the 923 participants, 36.8% were unexposed, 53.2% mildly exposed, and 10% highly exposed to paracetamol. Overall, prenatal exposure to paracetamol was not associated with CP. Sensitivity and subgroup analyses showed no clear associations between paracetamol and CP across strata of term/preterm birth as well as subtypes of CP.
CONCLUSIONS: The present study does not support an association between intrauterine exposure to paracetamol in early pregnancy and the risk of CP. However, it is important to stress that the exposure estimate is based on a single serum sample.

UNASSIGNED: Paracetamol (PCM) has an anti-shivering effect and may also exacerbate intraoperative hypothermia. This study compares the incidence of shivering as the primary outcome and the incidence of perioperative hypothermia (<36°C) and the time to the analgesic requirement as secondary outcomes when PCM was administered after induction of anaesthesia or towards the end of surgery.
UNASSIGNED: In this randomised study, 225 adult patients of either gender undergoing elective surgical procedures under general anaesthesia with an expected duration of surgery of 1-4 h were studied. They received intravenous (IV) PCM 15 mg/kg (maximum 1 g) immediately after anaesthesia induction (Early PCM group), 30 min before completion of surgery (Late PCM group) or no PCM (Control group). IV morphine 0.1 mg/kg was administered for analgesia in all three groups. The Chi-square test and repeated measures analysis of variance followed by Tukey\'s test were used for statistical analysis.
UNASSIGNED: The incidence of shivering was lower in Late PCM (12%) than in Early PCM (29.3%) (P = 0.009) and Control groups (30.6%) (P = 0.005). The incidence of postoperative hypothermia was also significantly lower in the Late PCM group than in the Early PCM (P = 0.002) and Control groups (P = 0.016). Early PCM and Control groups did not significantly differ. The number of patients requiring postoperative analgesia was smaller, and the time to the analgesic requirement was longer in Late PCM compared to other groups.
UNASSIGNED: Administration of IV PCM 30 min before completion of surgery results in a lower incidence of postoperative shivering and hypothermia when compared to PCM administered after induction of anaesthesia or no PCM.

OBJECTIVE: To estimate the prevalence of the paracetamol use for a reason other than pain (qualitative misuse) during the last 12 months in patients consulting their general practitioner, as well as the reasons for this misuse.
METHODS: Descriptive cross-sectional analysis, with gender weighting to estimate the prevalence of paracetamol misuse.
RESULTS: In total, data from 209 patients were included in the analysis. Among them, 11 patients declared having taken paracetamol for a reason other than pain, i.e., a gender-weighted prevalence of 5.7% (95% CI: 3.0 to 10.4). Nearly two-thirds of these patients said they had done it to feel better.
CONCLUSIONS: The paracetamol misuse is rare but real in general practice. Further studies are needed to better understand it, especially qualitative studies.

Minitablets are prepared using multiple die openings and multi-tip punches for greater productivity. With multiple tips on the punch barrel, the overall compaction force to be applied is commonly estimated by multiplying the desired compaction force per tip by the number of punch tips. Few researchers have however examined this proportionality and the effects of the number of punch tips and punch face geometry on the critical quality attributes (CQAs) of high drug load minitablets. In this study, the minitablets prepared by multi-tip tools exhibited greater weight variation than those prepared by single-tip tools. Their compaction was accompanied by a longer dwell time that led to a higher minitablet tensile strength and consequently a longer disintegration time. The compaction forces required to achieve a consistent set of minitablet CQAs were not directly proportional to the number of punch tips used. In comparison, the effect of punch face geometry was negligible. Increasing concentration of magnesium stearate (as lubricant) from 0.75 to 1.25 %, w/w reduced weight variation, especially of minitablets prepared by the multi-tip tools. It also increased the disintegration time but had no significant effect on the tensile strength of the minitablets regardless of type of tools used. The adjustment of compaction speed was an effective compensatory method to mitigate the differences in dwell time and tensile strength between minitablets prepared by single-tip and multi-tip standard concave tools. A larger reduction in compaction speed of the single-tip tools was required at higher compaction pressures.

BACKGROUND: Paracetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer.
METHODS: This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up.
RESULTS: During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06-1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up.
CONCLUSIONS: The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.

Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain.
This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events.
In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method.
Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS.
The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).

BACKGROUND: Prophylactic paracetamol for extremely low gestation age neonates (ELGAN, <27 weeks\' gestation) with symptomatic patent ductus arteriosus (sPDA) in high-income countries (HIC) reduces medical and surgical interventions. Its effectiveness in low-to-middle-income countries (LMIC) remains uncertain. This study assesses prophylactic paracetamol\'s impact on sPDA interventions in ELGANs in an LMIC.
METHODS: This is a retrospective cohort study that compared a historical cohort of ELGANs that were treated with oral ibuprofen or intravenous paracetamol after diagnosis of sPDA (n = 104) with infants (n = 76) treated with prophylactic paracetamol (20 mg/kg loading, 7.5 mg/kg qid for 4 days), in a tertiary neonatal intensive care unit (NICU) in Vietnam. Oral ibuprofen or intravenous therapeutic paracetamol were administered if prophylactic paracetamol failed to close sPDA. Surgical ligation was conducted if targeted medical intervention failed, or the infant deteriorated from conditions attributable to sPDA.
RESULTS: In the historical cohort, 57 (55%) infants died within 7 days of life compared to 18 (24%) from the prophylactic cohort (p < 0.01). Of the survivors, 21 (45%) of the historical and 23 (39.7%) of the prophylactic cohort required surgical ligation (p = 0.6). Duration of hospitalization for survivors was lower in the prophylactic cohort (mean 74 vs. 97 days, p = 0.01). In the prophylactic cohort, 24 (41%) infants did not need further treatment while 34 (59%) required further treatment including ibuprofen and/or paracetamol 28 (48%) and surgical ligation 22 (38%).
CONCLUSIONS: Prophylactic paracetamol for ELGAN in LMIC does not reduce the need for surgical ligation, sPDA rates, and other PDA-related morbidities in infants who survive beyond 7 days of age. It may reduce the risk of death and the duration of hospitalization but further study into the reasons behind this need to be determined with larger studies.