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In this prospective study, we compared the efficacy and side effects of indomethacin, ibuprofen, and paracetamol in patent ductus arteriosus (PDA) closure in preterm neonates. Three hundred preterm neonates with hemodynamically significant PDA (hs-PDA) admitted at our neonatal intensive care unit were enrolled in the study. They were randomized into three groups. Group I (paracetamol group) received 15 mg/kg/6 h IV paracetamol infusion for 3 days. Group II (ibuprofen group) received 10 mg/kg IV ibuprofen infusion followed by 5 mg/kg/day for 2 days. Group III (indomethacin group) received 0.2 mg/kg/12 h indomethacin IV infusion for three doses. Laboratory investigations such as renal function test, liver function test, complete blood count, and blood gases were conducted in addition to echocardiographic examinations. All investigations were done before and 3 days after treatment. There was no significant difference between all groups regarding efficacy of PDA closure ( P  = 0.868). There was a significant increase in serum creatinine levels and serum blood urea nitrogen (BUN) in the ibuprofen and indomethacin groups ( P  < 0.001). There was a significant reduction in platelet count and urine output (UOP) in both ibuprofen and indomethacin groups ( P  < 0.001). There was a significant increase in bilirubin levels in only the ibuprofen group ( P  = 0.003). No significant difference of hemoglobin (HB) level or liver enzymes in all groups ( P  > 0.05). Ventilatory settings improved significantly in patients with successful closure of PDA than those with failed PDA closure ( P  < 0.001). Conclusion : Paracetamol is as effective as indomethacin and ibuprofen in closure of PDA in preterm neonates and has less side effects mainly on renal function, platelet count, and GIT bleeding. What is Known: • Hemodynamically significant patent ductus arteriosus has many complications for preterm and low birth weight neonates and better to be closed. Many drugs were used for medical closure of PDA e.g. indomethacin, ibuprofen and recently paracetamol. Many studies compare safety and efficacy of paracetamol with either indomethacin or ibuprofen. What is New: • It is the first large study that compares the efficacy and side effects of the three drugs in one study.

PurposeEffect size estimates of analgesic drugs can be misleading. Ibuprofen (400 mg, 600 mg, 800 mg), paracetamol (1000 mg, 500 mg), paracetamol 1000 mg/codeine 60 mg, and placebo were investigated to establish the multidimensional pharmacodynamic profiles of each drug on acute pain with calculated effect size estimates.MethodsA randomized, double-blind, single-dose, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 350 patients (mean age 25 year, range 18 to 30 years) of homogenous ethnicity after third molar surgery. Primary outcome was sum pain intensity over 6 h. Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference, maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat values, adverse effects, overall drug assessment as patient-reported outcome measure (PROM), and the effect size estimates NNT and NNTp.ResultsIbuprofen doses above 400 mg do not significantly increase analgesic effect. Paracetamol has a very flat analgesic dose–response profile. Paracetamol 1000/codeine 60 mg gives similar analgesia as ibuprofen from 400 mg, but has a shorter time to analgesic onset. Active drugs show no significant difference in maximal analgesic effect. Other secondary outcomes support these findings. The frequencies of adverse effects were low, mild to moderate in all active groups. NNT and NTTp values did not coincide well with PROMs.ConclusionIbuprofen doses above 400 mg for acute pain offer limited analgesic gain. Paracetamol 1000 mg/codeine 60 mg is comparable to ibuprofen doses from 400 mg. Calculated effect size estimates and PROM in our study seem not to relate well as clinical analgesic efficacy estimators.Trial registrationNCT00699114.

Background To compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA). Methods In this randomized, non-inferiority, controlled clinical study, patients of knee OA were randomized to receive bioavailable turmeric extract (BCM-95®) 500 mg capsule two times daily or paracetamol 650 mg tablet three times daily for 6 weeks. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The secondary outcome measures were WOMAC total, WOMAC stiffness, and WOMAC physical function scores. Responder analysis of individual patients at different levels (≥ 20%, ≥ 50%, and ≥ 70%) for WOMAC score was calculated. TNF alpha and CRP levels were evaluated and adverse events (AE) were also recorded. Results Seventy-one and seventy-three knee OA patients, respectively in bioavailable turmeric extract and paracetamol groups, completed the study. Non-inferiority (equivalence) test showed that WOMAC scores were equivalent in both the groups ( p value < 0.05) in all the domains within the equivalence limit defined by effect size (Cohen’s d ) of 0.5 whereas CRP and TNF-α were better reduced with turmeric extract than paracetamol. After 6 weeks of treatment, WOMAC total score, pain, stiffness, and function scores got a significant improvement of 23.59, 32.09, 28.5, and 20.25% respectively with turmeric extract. In the turmeric extract group, 18% of patients got more than 50% improvement and 3% of patients got more than 70% improvement in WOMAC pain and function/stiffness score and none of the patients in the paracetamol group met the criteria. CRP and TNF-α got significantly reduced (37.21 and 74.81% respectively) in the turmeric extract group. Adverse events reported were mild and comparatively less in the turmeric extract group (5.48%) than in the paracetamol group (12.68%). Conclusion The results of the study suggest that bioavailable turmeric extract is as effective as paracetamol in reducing pain and other symptoms of knee osteoarthritis and found to be safe and more effective in reducing CRP and TNF-α. Trial registration Clinical Trials Registry – India CTRI/2017/02/007962 . Registered on 27 February 2017

Objectives To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain. Methods A randomised, double-blind, four-arm, parallel-group, active controlled trial investigating short-term (day 10) and long-term (week 13) benefits and side-effects of four regimens, each taken three times a day: ibuprofen (400 mg); paracetamol (1000 mg); one fixed-dose combination tablet (ibuprofen 200 mg/paracetamol 500 mg); two fixed-dose combination tablets (ibuprofen 400 mg/paracetamol 1000 mg). Results There were 892 participants (mean age 60.6, range 40–84 years); 63% had radiographic knee osteoarthritis and 85% fulfilled American College of Rheumatology criteria for osteoarthritis. At day 10, two combination tablets were superior to paracetamol (p<0.01) for pain relief (determined by mean change from baseline in WOMAC pain; n=786). At 13 weeks, significantly more participants taking one or two combination tablets rated their treatment as excellent/good compared with paracetamol (p=0.015, p=0.0002, respectively; n=615). The frequency of adverse events was comparable between groups. However, by 13 weeks, decreases in haemoglobin (≥1 g/dl) were observed in some participants in all groups. Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy (p<0.001; paracetamol, 20.3%; ibuprofen, 19.6%; one or two combination tablets, 24.1%, 38.4%, respectively). Conclusions Ibuprofen/paracetamol combination analgesia, at non-prescription doses, confers modest short-term benefits for knee pain/osteoarthritis. However, in this population, paracetamol 3 g/day may cause similar degrees of blood loss as ibuprofen 1200 mg/day, and the combination of the two appears to be additive. Study no ISRCTN77199439

Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has been presented as a broad-spectrum antiviral agent. This randomised clinical trial in a hospital setting evaluated the efficacy and safety of this drug in RT-PCR-positive coronavirus disease 2019 (COVID-19) patients. A total of 210 RT-PCR-positive COVID-19 patients who provided consent were allotted to the control or case arm, based on block randomisation. The control arm received standard of care comprising paracetamol, ivermectin, and other adjuvant therapies. The patients in the case arm received indomethacin instead of paracetamol, with other medications retained. The primary endpoint was the development of hypoxia/desaturation with SpO 2  ≤ 93, while time to become afebrile and time for cough and myalgia resolution were the secondary endpoints. The results of 210 patients were available, with 103 and 107 patients in the indomethacin and paracetamol arms, respectively. We monitored patient profiles along with everyday clinical parameters. In addition, blood chemistry at the time of admission and discharge was assessed. As no one in either of the arms required high-flow oxygen, desaturation with a SpO 2 level of 93 and below was the vital goal. In the indomethacin group, none of the 103 patients developed desaturation. On the other hand, 20 of the 107 patients in the paracetamol arm developed desaturation. Patients who received indomethacin also experienced more rapid symptomatic relief than those in the paracetamol arm, with most symptoms disappearing in half the time. In addition, 56 out of 107 in the paracetamol arm had fever on the seventh day, while no patient in the indomethacin group had fever. Neither arm reported any adverse event. The fourteenth-day follow-up revealed that the paracetamol arm patients had faced several discomforts; indomethacin arm patients mostly complained only of tiredness. Indomethacin is a safe and effective drug for treating patients with mild and moderate covid-19.

BackgroundLaparoscopic sleeve gastrectomy (LSG) is defined as the first-step bariatric surgery for the treatment of obesity. Opioid analgesics are often preferred for pain management because of their strong analgesic potentials. However, opioids have undesirable adverse effects.ObjectivesThe objective of this study is to evaluate and compare the influence of IV forms of ibuprofen and paracetamol on pain management and opioid consumption on patients undergoing LSG surgery.SettingThis study was conducted at Istanbul Medipol University Hospital.MethodsPatients were stratified into three groups. Group I (group ibuprofen, n = 30) was administered 800 mg of IV ibuprofen, group P (group paracetamol, n = 30) was administered 1000 mg of IV paracetamol, and group C (control group, n = 30) was given 100 ml of saline solution. We evaluated opioid consumption and VAS scores postoperatively.ResultsThis study included 90 patients who underwent LSG. The use of rescue medication in group I was statistically lower than the other groups. VAS scores in group I and group P at recovery and at 2, 4, 8, 12, and 24 h were lower than those in group C. In particular, the VAS scores in group I at the first 2 h postoperatively were significantly lower than those in group P (p < 0.05). Opioid consumption in group C was significantly higher than the other groups (p < 0.05).ConclusionOur study suggested that IV ibuprofen resulted in lower pain scores compared to paracetamol by reducing postoperative opioid use in the first 24 h in patients undergoing LSG surgery.

There has been concern that acetaminophen may exacerbate asthma. These investigators found no difference in asthma control among young children treated for minor illnesses with acetaminophen as compared with ibuprofen. Many children younger than 12 years of age receive acetaminophen each week, making it the most commonly used pediatric medication in the United States. 1 Observational data from both pediatric and adult cohorts have suggested an association between acetaminophen use and concurrent asthma symptoms and decreased lung function. 2 – 6 Furthermore, a post hoc analysis of a randomized trial on the safety of short-term use of acetaminophen versus ibuprofen for febrile illnesses in children similarly showed that the relative risk of unscheduled visits for asthma after the use of acetaminophen was substantially higher than the risk after the use of ibuprofen. 7 These . . .

Acetaminophen, an effective and popular over-the-counter pain reliever (e.g., the active ingredient in Tylenol), has recently been shown to blunt individuals' reactivity to a range of negative stimuli in addition to physical pain. Because accumulating research has shown that individuals' reactivity to both negative and positive stimuli can be influenced by a single factor (an idea known as differential susceptibility), we conducted two experiments testing whether acetaminophen blunted individuals' evaluations of and emotional reactions to both negative and positive images from the International Affective Picture System. Participants who took acetaminophen evaluated unpleasant stimuli less negatively and pleasant stimuli less positively, compared with participants who took a placebo. Participants in the acetaminophen condition also rated both negative and positive stimuli as less emotionally arousing than did participants in the placebo condition (Studies 1 and 2), whereas nonevaluative ratings (extent of color saturation in each image; Study 2) were not affected by drug condition. These findings suggest that acetaminophen has a general blunting effect on individuals' evaluative and emotional processing, irrespective of negative or positive valence.

PurposeCombining analgesics with different mechanisms of action may increase the analgesic efficacy. The multidimensional pharmacodynamic profiles of ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 400 mg/paracetamol 1000 mg/codeine 60 mg, and paracetamol 1000 mg/codeine 60 mg and placebo were compared.MethodsA randomized, double-blind, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 200 patients of both sexes and homogenous ethnicity after third molar surgery (mean age 24 years, range 19–30 years). Primary outcome was sum pain intensity over 6 h (SPI). Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference (SPID), maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat, prevent remedication and harm values, adverse effects, and patient-reported outcome measure (PROM).ResultsAnalgesia following ibuprofen and paracetamol combination with or without codeine was comparable. Both were better than paracetamol combined with codeine. Secondary variables supported this finding. Post hoc analysis of SPI and SPID revealed a sex/drug interaction trend in the codeine-containing groups where females experienced less analgesia. PROM showed a significant sex/drug interaction in the paracetamol and codeine group, but not in the other codeine-containing group. Especially females reported known and mild side effects in the codeine-containing groups.ConclusionCodeine added to ibuprofen/paracetamol does not seem to add analgesia in a sex-mixed study population. Sex may be a confounding factor when testing weak opioid analgesics such as codeine. PROM seems to be more sensitive than traditional outcome measures.Trial registrationClinicalTrials.gov June 2009 NCT00921700.

Background Persistent patency of the ductus arteriosus (PDA) has challenged neonatologists for more than 40 years. Controversies persist about the management of PDA in extremely preterm infants. PDA is associated with morbidities, but no therapeutic strategy has resulted in an improved neonatal outcome. Acetaminophen appears to be a promising alternative with possibly fewer adverse effects. The primary objective is to determine whether a prophylactic pharmacological intervention with acetaminophen may increase the survival without severe morbidity at postmenstrual age of 36 weeks. Methods and analysis TREOCAPA phase III is a randomized, multicenter, double-blind, stratified, placebo-controlled superiority trial, two arms in a 1:1 ratio performed in 43 NICUs of 14 European countries, evaluating whether the intervention increases the survival without severe morbidity by 10%, from 50% in control arm to 60% in treatment arm, until the age of 36 postmenstrual weeks. To detect this difference, 794 patients were required using a group sequential design. Recruitment has been closed, with 803 patients enrolled. Patients eligible for inclusion are preterm infants with a gestational age between 23 and 28 weeks. In the acetaminophen group, 20 mg/kg loading dose within 12 h after birth, followed by 7.5 mg/kg quarter in die (QID) for 5 days, will be administered to the 27–28 weeks gestational age group, and 25 mg/kg loading dose then 10 mg/kg QID will be administered to the 23–26 weeks gestational age group. The severe morbidities include severe bronchopulmonary dysplasia (BPD grade 3) according to NIH consensus, necrotizing enterocolitis (NEC) of Bell’s stage II or III, intraventricular hemorrhage (IVH) grade III–IV according to Papile classification, or cystic leukomalacia. Discussion Whatever the results, the conclusions of this study should be informative for the neonatal scientific community. The results will either confirm the benefit of treatment in increasing survival without severe morbidity, or indicate a worsening of outcomes with prophylactic acetaminophen treatment, or show no difference in the primary outcome. In the latter case, ultrasonographic assessments of ductus arteriosus status on day 7 may help explain the absence of a difference. This could indicate that acetaminophen is ineffective in promoting ductal closure or that early closure of the ductus arteriosus is inconsequential if, despite more frequent closures, there is no associated improvement in outcomes. Ethics and dissemination Ethical approval of the trial has been performed in each of the 14 countries after approval, at the European level, by the Voluntary Harmonization Procedure committee on 04/07/2020. Results will be disseminated through articles in peer-reviewed journals. Trial registration European Clinical Trials Database: EudraCT Number: 2019–004297-26. ClinicalTrials.gov: NCT04459117, registered on July 7, 2020.