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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.

BackgroundRecent meta-analyses suggested diclofenac may be superior to indomethacin in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The aim of our study was to compare the efficacy of 100 mg rectal indomethacin versus diclofenac on PEP incidences.DesignThis multicentre, double-blinded, randomised controlled trial was conducted in nine tertiary centres in China. Patients with low and high risk for PEP and native papilla were randomly allocated (1:1) to receive 100 mg diclofenac or 100 mg indomethacin rectally before ERCP. The primary outcome was the occurrence of PEP defined by the Cotton consensus. The intention-to-treat principle was conducted for the analysis.ResultsThe trial was terminated early for futility after the predetermined first interim analysis. Between June 2023 and May 2024, 1204 patients were randomised into the diclofenac group (n=600) or indomethacin group (n=604). Baseline characteristics were balanced. The primary outcome occurred in 53 patients (8.8%) of 600 patients allocated to the diclofenac group and 37 patients (6.1%) of 604 patients allocated to the indomethacin group (relative risk 1.44; 95% CI 0.96 to 2.16, p=0.074). PEP occurred in 35 (14.2%) of 247 high-risk patients in the diclofenac group and 26 (9.8%) of 266 high-risk patients in the indomethacin group (p=0.124). PEP incidences were also comparable in low-risk patients between the two groups (18/353 (5.1%) vs 11/338 (3.3%), p=0.227). Other ERCP-related complications did not differ between the two groups.ConclusionPre-procedure 100 mg rectal diclofenac was not superior to the same dose of rectal indomethacin regarding preventing PEP. These findings supported current clinical practice guidelines of 100 mg indomethacin or diclofenac for PEP prophylaxis in patients without contraindications.Trial registration numberClinicalTrials.gov (NCT05947461).

Rectal indometacin decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the population most at risk and the optimal timing of administration require further investigation. We aimed to assess whether pre-procedural administration of rectal indometacin in all patients is more effective than post-procedural use in only high-risk patients to prevent post-ERCP pancreatitis. We did a multicentre, single-blinded, randomised controlled trial at six centres in China. Eligible patients with native papilla undergoing ERCP were randomly assigned in a 1:1 ratio (with a computer-generated list) to universal pre-procedural indometacin or post-procedural indometacin in only high-risk patients, with stratification by trial centres and block size of ten. In the universal indometacin group, all patients received a single dose (100 mg) of rectal indometacin within 30 min before ERCP. In the risk-stratified, post-procedural indometacin group, only patients at predicted high risk received rectal indometacin, immediately after ERCP. Investigators, but not patients, were masked to group allocation. The primary outcome was overall ocurrence of post-ERCP pancreatitis. The analysis followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT02002650. Between Dec 15, 2013, and Sept 21, 2015, 2600 patients were randomly assigned to universal, pre-procedural indometacin (n=1297) or risk-stratified, post-procedural indometacin (n=1303). Overall, post-ERCP pancreatitis occurred in 47 (4%) of 1297 patients assigned to universal indometacin and 100 (8%) of 1303 patients assigned to risk-stratified indometacin (relative risk 0·47; 95% CI 0·34–0·66; p<0·0001). Post-ERCP pancreatitis occurred in 18 (6%) of 305 high-risk patients in the universal group and 35 (12%) of 281 high-risk patients in the risk-stratified group (p=0·0057). Post-ERCP pancreatitis was also less frequent in average-risk patients in the universal group (3% [29/992]), in which they received indometacin, than in the risk-stratified group (6% [65/1022]), in which they did not receive the drug (p=0·0003). Other than pancreatitis, adverse events occurred in 41 (3%; two severe) patients in the universal indometacin group and 48 (4%; one severe) patients in the risk-stratified group. The most common adverse events were biliary infection (22 [2%] patients vs 33 [3%] patients) and gastrointestinal bleeding (13 [1%] vs ten [1%]). Compared with a risk-stratified, post-procedural strategy, pre-procedural administration of rectal indometacin in unselected patients reduced the overall occurrence of post-ERCP pancreatitis without increasing risk of bleeding. Our results favour the routine use of rectal indometacin in patients without contraindications before ERCP. National Key Technology R&D Program, National Natural Science Foundation of China.

INTRODUCTION:Chronic pancreatitis (CP) remains difficult to manage with few treatment options. Prior studies have implicated prostaglandin E2 (PGE2) in mediating chronic inflammation in the pancreas. Therefore, we aimed to evaluate whether indomethacin, a cyclooxygenase-2 enzyme inhibitor, would reduce PGE2 levels in CP.METHODS:In this pilot multicenter randomized controlled trial, participants with CP received oral indomethacin (50 mg) or placebo twice daily for 28 days. Measurement of PGE2 levels in pancreatic fluid collected endoscopically after secretin administration at baseline and posttreatment (day 28) was performed. Quality of life and pain were also assessed at baseline and posttreatment.RESULTS:A total of 27 participants were randomized (indomethacin = 13, placebo = 14). Although PGE2 levels decreased after treatment in pancreas fluid, plasma, and saliva in the indomethacin group, there was no significant difference in mean change in pancreas fluid PGE2 levels between the indomethacin and placebo groups (−457.7 pg/mL vs −840.4 pg/mL, P = 0.25). There was also no significant change in pain severity composite score (−1.3 indomethacin vs −0.5 placebo, P = 0.33), but the improvement in pain interference score (−2.9 indomethacin vs −0.4, P = 0.058) trended toward significance. There was no difference in adverse events between the 2 groups.DISCUSSION:In this phase 1/2 study, oral indomethacin was safe and well tolerated by patients with CP. Although there was no significant difference in change in PGE2 levels, further studies are needed to determine the effect of indomethacin on the inflammatory pathway of CP and patient-centered outcomes.

Background Acute pancreatitis is the most common major complication after endoscopic retrograde cholangiopancreatography (ERCP). Many drugs have been evaluated for prophylaxis, including nonsteroidal anti-inflammatory drugs (NSAIDs), which are potent inhibitors of phospholipase A 2 and play a role in the pathogenesis of acute pancreatitis. Rectal NSAIDs have been shown in prospective studies to decrease the incidence of this complication, but the indication is not generalized in clinical practice. The aim of this study was to evaluate the efficacy of rectal administration of indomethacin in reducing the incidence of post-ERCP pancreatitis in high-risk patients. Methods This was a controlled clinical trial where patients with an elevated risk of developing post-ERCP pancreatitis were assigned to receive 100 mg of rectal indomethacin or a 2.6 g suppository of glycerin immediately after ERCP, without placement of a pancreatic stent. The patients were determined to be at high risk based on validated patient- and procedure-related risk factors. Post-ERCP pancreatitis was defined as the presence of new upper abdominal pain, hyperamylasemia/hyperlipasemia (at least three times the upper limit) 2 hours after the procedure and hospitalization at least 48 hours because of the complication. Pancreatitis severity was defined according to Cotton’s criteria. Results One hundred sixty-six patients were included; 82 in the study group and 84 in the placebo group. Patients had at least one major and/or two minor risk factors for developing post-ERCP pancreatitis. The incidence of the complication was 4.87 % (4/82) in the study group and 20.23 % (17/84) in the placebo group; this difference was significant ( P  = 0.01). According to Cotton’s criteria, 17 patients (80.9 %) developed mild pancreatitis and 4 (19.1 %) had moderate pancreatitis; 3 of these 4 patients belonged to the placebo group ( P  = 0.60). Based on these results, an absolute risk reduction of 0.15 (15 %), a relative risk reduction of 0.75 (75 %) and a number needed to treat of 6.5 patients were calculated to prevent an episode of post-ERCP pancreatitis. There was no mortality. Conclusions Rectal indomethacin reduced the incidence of post-ERCP pancreatitis among patients at high risk of developing this complication. Trial registration National Clinical Trials NCT02110810 . Date April 7, 2014.

Background Short-term outcomes of laparoscopy-assisted distal gastrectomy (LADG) and open DG (ODG) have been investigated in previous clinical trials, but operative techniques and concomitant treatments have evolved, and up-to-date evidence produced by expert surgeons is required to provide an accurate image of the relative efficacies of the treatments. The purpose of this study was to compare laparoscopic versus ODG with respect to specific primary and secondary short-term outcomes. Methods From October 2005 to February 2008, a total of 64 patients with early gastric cancer were randomly assigned to the LADG or the ODG group. One patient was excluded due to concurrent illness unrelated to the intervention, so the data from 63 patients were analyzed. The primary short-term outcome was the 4-day postoperative use of analgesics. Secondary short-term outcomes were postoperative residual pain, complications, days hospitalized, blood data, days with fever, and days to first flatus. Results There was a significant difference in favor of LADG for postoperative use of analgesics ( P  = 0.022). Unexpectedly, there was no significant difference in degree of pain in the immediate postoperative period, putatively due to the optimal use of analgesics. Of the secondary outcomes, residual pain at postoperative day 7 ( P  = 0.003) and days to first flatus ( P  = 0.001) were significantly better with LADG. Postoperative complications, number of days hospitalized, and number of days with fever were also better with LADG, but the differences were not significant. Blood data representing inflammation (WBC and CRP) showed marked differences, especially on postoperative day 7 ( P  = 0.0016 and P  = 0.0061, respectively). Conclusions LADG performed by expert surgeons results in less postoperative pain accompanied by decreased surgical invasiveness and is associated with fewer postoperative inconveniences. No preliminary suggestions of changes in long-term curability were observed. LADG for early gastric cancer is a feasible and safe procedure with short-term clinical results superior to those of ODG.

Background The combination of prophylactic pancreatic stent placement (PSP) – a temporary plastic stent placed in the pancreatic duct – and rectal non-steroidal anti-inflammatory drugs (NSAIDs) is recommended for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Preliminary data, however, suggest that PSP may be unnecessary if rectal NSAIDs are administered. Given the costs and potential risks of PSP, we aim to determine whether rectal indomethacin obviates the need for pancreatic stent placement in patients undergoing high-risk ERCP. Methods/Design The SVI (Stent vs. Indomethacin) trial is a comparative effectiveness, multicenter, randomized, double-blind, non-inferiority study of rectal indomethacin alone versus the combination of rectal indomethacin and PSP for preventing PEP in high-risk cases. One thousand four hundred and thirty subjects undergoing high-risk ERCP, in whom PSP is planned solely for PEP prevention, will be randomized to indomethacin alone or combination therapy. Those who are aware of study group assignment, including the endoscopist, will not be involved in the post-procedure care of the patient for at least 48 hours. Subjects will be assessed for PEP and its severity by a panel of independent and blinded adjudicators. Indomethacin alone will be declared non-inferior to combination therapy if the two-sided 95 % upper confidence bound of the treatment difference is less than 5 % between the two groups. Biological specimens will be obtained from trial participants and centrally banked. Discussion The SVI trial is designed to determine whether PSP remains necessary in the era of NSAIDs pharmacoprevention. The associated bio-repository will establish the groundwork for important scientific breakthrough. Trial registration NCT02476279, registered June 2015.

Experimental data suggest that nonsteroidal antiinflammatory drugs may prevent disease severity and mortality in acute pancreatitis (AP). The aim of this study was to compare the efficacy of rectal indomethacin vs placebo in reducing the systemic inflammatory response syndrome (SIRS) score in a high-risk AP population for clinical progression. We conducted a single-center, quadruple-blinded, randomized, placebo-controlled trial. Eligible criteria were subjects with AP and SIRS within 72 hours of presentation and those without organ failure. Subjects were allocated in a 1:1 ratio to indomethacin or placebo using simple randomization. Both interventions were administered rectally every 8 hours for 6 doses and compared using both intention-to-treat and per-protocol analyses. A total of 42 subjects (mean age 52 years, 55% men) were randomized to indomethacin (n = 18) or placebo (n = 24). There was no significant difference between the indomethacin and placebo groups in the change of SIRS score, proportion of subjects with SIRS, and distribution of SIRS scores at 24, 48, and 72 hours from randomization. There were no significant differences in the change of C-reactive protein levels at 48 hours or clinical outcomes between both treatment groups. Indomethacin was as safe as placebo, with 2 adverse events occurring in the placebo and none in the indomethacin arm. Rectal indomethacin can be safely administered over 48 hours; however, it is not superior to placebo in reducing the SIRS or clinical progression in a high-risk population with AP (ClinicalTrials.gov: NCT02692391).

To compare the concentrations of interleukin (IL) (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and TNF-β in the aqueous humor of patients undergoing femtosecond laser-assisted cataract surgery (FLACS) and corneal mechanical paracentesis treated with two different topical nonsteroidal anti-inflammatory drugs (NSAIDs): bromfenac and indomethacin. In this prospective, randomized controlled, single-center study, aqueous humor samples were obtained immediately after performing the femtosecond laser procedure or at the start of conventional phacoemulsification. Preoperatively, the FLACS groups were administered (once daily and four times daily, respectively) either topical bromfenac 0.09% (12 eyes) or indomethacin 0.1% (12 eyes). The corneal paracentesis bromfenac and indomethacin groups received the same regimen of instillation of NSAIDs, respectively. Quantitative analysis of the expressed cytokines in the aqueous humor was performed using FlowCytomix FC 500 Pro 3.0 Software (Bender MedSystems GmbH, Vienna, Austria). The intraoperative pupil diameter was correlated with the expression of IL-6 after the femtosecond laser procedure in the FLACS indomethacin group (r = -0.53; P = .07). A significant difference in mean pupillary size was detected between the FLACS bromfenac and indomethacin groups at the aspiration/irrigation time point (0.53 ± 0.26 mm) and at the end of surgery (0.68 ± 0.37 mm). Progressive pupillary constriction was observed in the indomethacin and bromfenac groups. A smaller expression of IL-6 to the overall cytokine network value was observed in cases receiving preoperative bromfenac 0.09%, explaining improved maintenance of intraoperative mydriasis. [J Refract Surg. 2018;34(10):646-652.].