An Evaluation of the Effects of Pineapple-Extract and Bromelain-Based Treatment after Mandibular Third Molar Surgery: A Randomized Three-Arm Clinical Study.

A three-arm, randomized, placebo-controlled clinical study was conducted to assess the impact of lyophilized pineapple extract with titrated bromelain (Brome-Inf®) and purified bromelain on pain, swelling, trismus, and quality of life (QoL) following the surgical extraction of the mandibular third molars. Furthermore, this study examined the need for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by comparing their effects with a placebo group. This study enrolled 42 individuals requiring the extraction of a single mandibular third molar under local anesthesia. The patients were randomly assigned to receive Brome-Inf®, purified bromelain, or a placebo orally, initiating treatment on the day of surgery and continuing for the next 7 days. The primary outcome measured was the requirement for NSAIDs in the three groups. Pain, swelling, and trismus were secondary outcome variables, evaluated postoperatively at 1, 3, and 7 days. This study also assessed the comparative efficacy of freeze-dried pineapple extract and single-component bromelain. Ultimately, the placebo group showed a statistically higher need for ibuprofen (from days 1 to 7) at the study's conclusion (p < 0.0001). In addition, reductions in pain and swelling were significantly higher in both the bromelain and pineapple groups (p < 0.0001 for almost all patients, at all intervals) than in the placebo group. The active groups also demonstrated a significant difference in QoL compared to the placebo group (p < 0.001). A non-significant reduction in trismus occurred in the treatment groups compared to the placebo group. Therefore, the administration of pineapple extract titrated in bromelain showed significant analgesic and anti-edema effects in addition to improving QoL in the postoperative period for patients who had undergone mandibular third molar surgery. Moreover, both bromelain and Brome-Inf® supplementation reduced the need for ibuprofen to comparable extents, proving that they are good alternatives to NSAIDs in making the postoperative course more comfortable for these patients. A further investigation with larger samples is necessary to assess the pain-relieving and anti-inflammatory impacts of the entire pineapple phytocomplex in surgical procedures aside from mandibular third molar surgery.

Chiropractic spinal manipulative therapy for acute neck pain: A 4-arm clinical placebo randomized controlled trial. A prospective study protocol.

INTRODUCTION: Neck pain poses enormous individual and societal costs worldwide. Spinal manipulative therapy and Non-Steroidal Anti-Inflammatory Drug treatment are frequently used despite a lack of compelling efficacy data. This protocol describes a multicentre 4-arm, clinical placebo randomized controlled trial (RCT), investigating the efficacy of chiropractic spinal manipulative therapy (CSMT) versus sham CSMT, ibuprofen, and placebo medicine for acute neck pain. This superiority study will employ parallel groups, featuring a 1:1:1:1 allocation ratio. MATERIAL AND METHODS: We will randomize 320 participants equally into four groups: CSMT, sham CSMT, ibuprofen, or placebo medicine. CSMT groups are single-blinded, while the medicine groups are double-blinded. Data will be collected at baseline (Day 0), during treatment and post-treatment. The primary endpoint will assess the difference in mean pain intensity from Day 0 to Day 14 on a numeric rating scale 0-10; the CSMT group is compared to sham CSMT, ibuprofen, and placebo medicine groups, respectively. Secondary endpoints will assess mean pain intensity and mean duration at different time points, and adverse events, blinding success, and treatment satisfaction, including comparison between ibuprofen and placebo medicine. Power calculation is based on a mean neck pain rating of 5 at Day 0, with standard deviation of 1 in all groups. Mean pain reduction at Day 14 is expected to be 60% in the CSMT group, 40% in sham CSMT and ibuprofen groups, and 20% in the placebo medicine group. A linear mixed model will compare the mean values for groups with corresponding 95% confidence intervals. P values below 0.017 will be considered statistically significant. All analyses will be conducted blinded from group allocation. DISCUSSION: This RCT aims towards the highest research standards possible for manual-therapy RCTs owing to its two placebo arms. If CSMT and/or ibuprofen proves to be effective, it will provide evidence-based support for CSMT and/or ibuprofen for acute neck pain. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05374057. EU Clinical Trials Register: EudraCT number: 2021-005483-21.

Comparison of the analgesic effects of single-dose 75 mg oral pregabalin versus single-dose 400 mg oral ibuprofen after impacted third mandibular molar surgery: A randomized, double-blind, split-mouth clinical trial.

BACKGROUND: Pain is the most prevalent complication after dentoalveolar surgery. Failure in effective pain control could potentially lead to systemic sequels, such as tachycardia, hypertension, improper nutrition, and central sensitization. Pregabalin is a gamma-aminobutyric acid (GABA) analog with inhibitory and analgesic effects on the central nervous system (CNS). Prescribing gabapentinoids as complementary analgesics reduces the consumption of opioid and non-opioid analgesics, and consequently their side effects. OBJECTIVES: The main purpose of the present study was to compare the analgesic effects of pregabalin (single-dose 75 mg) vs. ibuprofen (single-dose 400 mg) on patients' pain levels after impacted third mandibular molar surgery. MATERIAL AND METHODS: In this randomized, double-blind, split-mouth clinical trial, 24 patients aged 19-34 years volunteered for 2 consecutive (1 month apart) third mandibular molar surgeries (the contralateral teeth). The patients were randomly placed into 2 groups: group G1 (n = 12) was prescribed pregabalin (single-dose 75 mg) after the 1st surgery and ibuprofen (single-dose 400 mg) after the 2nd surgery; and group G2 (n = 12) was prescribed the exact opposite of the G1 arrangement. During the first 24 h post-surgery, the patients recorded the number of complementary analgesics they took (single-dose 400 mg ibuprofen) and their level of pain on a visual analog scale (VAS) every 2 h. RESULTS: The average level of pain at 2 h post-surgery (T1) was significantly lower when pregabalin was prescribed (p < 0.05). Most patients needed complementary analgesics at 4 h post-surgery (T2). However, during the first 24 h post-surgery, the patients required significantly more complementary analgesics when ibuprofen was prescribed. CONCLUSIONS: In comparison with oral ibuprofen (single-dose 400 mg), oral pregabalin (single-dose 75 mg) had a stronger analgesic effect at 2 h after impacted third mandibular molar surgery (p < 0.05). Pregabalin resulted in a significantly lower consumption of complementary analgesics in the first 24 h post-surgery as compared to ibuprofen.

A randomized, placebo-controlled study of magnetic acupuncture for supplementary analgesia after laparoscopic appendectomy in children.

PURPOSE: Magnetic acupuncture (MA) is a noninvasive technique potentially useful for postoperative pain reduction. While anecdotal case series have reported analgesic effects, this has not been systematically studied. We evaluated the analgesic properties of supplemental MA versus placebo and standard treatment in children who underwent laparoscopic appendectomy (LA). METHODS: Children age 2-18 years who underwent LA for acute appendicitis were recruited from 2018 through 2020. Standardized postoperative pain medication including Ibuprofen, Acetaminophen, and narcotics were given as needed. Patients were randomized to 3 groups: Group 1 had adhesive acupuncture magnets placed on 5 predetermined meridian points for 48 h. Group 2 had corresponding non-magnetic adhesive metal disks placed in the same locations. Group 3 received no supplemental treatment. Pain was measured every 4 h using a 1-10 Visual-Analog-Scale (VAS). Cumulative demand of as-needed pain medication was calculated. Patients and families were handed open questionnaires upon discharge assessing satisfaction with treatment. RESULTS: A total of 126 patients were randomized. Groups were similar in age and gender distribution. Differences of means of cumulative VAS scores were significantly lower for group 1 (8.0,SD5.2) compared to group 2 (12.8,SD4.4; -4.8[95%CI -7.1 to -2.5], p < 0.01), and group 3 (19.8,SD7.7; -11.8[95%CI -15.0 to -8.6], p < 0.01). Cumulative acetaminophen and ibuprofen use per patient during the entire hospital stay was lower for group 1 (1510 mg, 20 mg) than for group 2 (2950 mg, 1800 mg), and group 3 (6100 mg; 2300 mg), respectively. In contrast to groups 2 and 3, none of the patients in group 1 asked for narcotics. Patients were highly satisfied with MA. CONCLUSIONS: Supplemental MA after LA in children had a beneficial effect on the postoperative pain perception and on-demand use of analgesics that could not be explained by placebo mechanism. MA is a safe, simple, and effective adjunct to standard postoperative care. Further studies are warranted. TYPE OF STUDY: Prospective randomized, placebo-controlled trial LEVEL OF EVIDENCE: Level I.

Effect of time-dependent ibuprofen administration on the post operatory after impacted third molar extraction: a cross-over randomized controlled trial.

PURPOSE: To evaluate time-dependent administration of ibuprofen in a lower third molar extraction model. METHODS: Eleven patients requiring bilateral surgical removal of lower third molars were recruited and randomized into a blinded crossover randomized controlled trial. For 3 days after surgery, the control group was prescribed ibuprofen 400 mg every 8 h. On the other hand, the experimental group received also ibuprofen 400 mg at breakfast and lunch, replacing the dinner intake with a placebo. Pain measurements (Visual Analog Scale from 0 to 10) were recorded at baseline, 24, 48, and 72 h postoperatively. Facial swelling and trismus were also measured at baseline, 24, and 72 h postoperatively. RESULTS: Postoperative swelling and pain perception did not show significative difference between the control and experimental groups at 24, 48, and 72 h. Trismus was significantly lower in the control group than in the experimental group at 72 h postoperatively (p = 0.008). Rescue medication consumption seemed to be comparable between groups. CONCLUSION: Eliminating night time ibuprofen might be insignificant for pain control after third molar extraction.

Ibuprofen treatment ameliorates memory deficits in rats with collagen-induced arthritis by normalizing aberrant MAPK/NF-κB and glutamatergic pathways.

Many studies have indicated that the risk of cognitive impairment is higher in patients with rheumatoid arthritis (RA). Additionally, patients with RA may have a lower incidence of cognitive impairment with long-term use of ibuprofen. This study was aimed at investigating the impacts of RA on memory function and the mechanisms that ibuprofen may exhibit to improve memory function in rats with collagen-induced arthritis (CIA). Ibuprofen (30 mg/kg) was given twice daily to CIA rats for two weeks starting from Day 18 following the first immunization. Memory function was measured by the Morris water maze (MWM) test and long-term potentiation (LTP). The proinflammatory cytokine levels and downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), were examined. Furthermore, the glutamatergic system, including glutamate transporters/receptors and brain extracellular levels of glutamate, was investigated. The results showed that the impaired learning memory in CIA rats, examined by the MWM test and LTP, can be ameliorated by ibuprofen treatment. Along with the improvement in memory deficits, ibuprofen attenuated both neuroinflammation and the associated elevated levels of phosphorylated p38, JNK, and p65 in the hippocampus of CIA rats. In addition, the decreased excitatory amino acid transporter 2 level, the increased extracellular glutamate, and the upregulated hippocampal NMDA receptor 2B of CIA rats were all normalized by ibuprofen treatment. These findings suggest that the effect of ibuprofen on the memory improvement in CIA rats is associated with the normalization of the activated MAPK and NF-κB pathways and the aberrant glutamatergic system.

2022 Taiwan Guidelines for Acute Treatment of Migraine.

The Taiwan Headache Society published its guidelines for acute migraine treatment in 2017. Since then, emerging drugs and treatment options have developed rapidly. The migraine-specific drugs gepants and ditans and several noninvasive neuromodulation devices have been approved for use in Europe and the United States. Although not all emerging drugs and treatment options have been approved for use in Taiwan, keeping pace with international trends and updating treatment guidelines are imperative. Therefore, the Treatment Guideline Subcommittee of the Taiwan Headache Society reviewed the quality of recent trials, evaluated the corresponding grade of evidence, and appraised the reported clinical efficacy to reach a new consensus. To ensure that the updated Taiwan guidelines are appropriate and feasible, the subcommittee also referred to the guidelines from the United States, Europe, Canada, and other countries concerning the main roles, recommendation levels, clinical efficacy, and adverse reactions of drugs for the acute migraine treatment. Several types of drugs are currently available for acute migraine treatment in Taiwan. These drugs can be categorized into migraine-specific and migraine-non-specific. Among them, migraine-specific triptans (oral or nasal spray formulations) and migraine-nonspecific acetaminophen and NSAIDs (diclofenac, ibuprofen, naproxen) are highly recommended because they are supported by strong evidence and demonstrate high efficacy. Prochlorperazine injection has been upgraded to a highly recommended level because of the rich clinical experience for this treatment. Ergotamine/caffeine remains a second-line drug because of its lower specificity and efficacy compared with triptans. High-dose aspirin was downgraded to rescue treatment because of potential gastrointestinal side effects. Although evidence supports the combination of oral tramadol and acetaminophen, this combination should be used as a rescue treatment due to concerns about dependence. Evidence supporting the use of intravenous tramadol or morphine is insufficient; therefore, their use is not recommended. As for non-pharmacological approaches, there are only limited controlled data. The choice of treatment for acute migraine attacks should follow the concept of "stratified care." For mild to moderate migraine attacks, oral NSAIDs are the first choice, with combination analgesics, intravenous/intramuscular NSAIDs as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine/caffeine compounds are recommended and should be administered in the early stage of migraine attacks. Antiemetics can be used as supplements to alleviate nausea and vomiting. Other emerging migraine-specific drugs, such as gepants or ditans, may also have a role in the future. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either therapy alone. Parenteral steroids and fluid supply are the first-line treatment for status migrainosus. Acetaminophen is suitable for mild to moderate migraine attacks and remains the first choice for children and pregnant women. To prevent medication overuse headache, the use of acute treatment should be limited to a maximum of 2 days per week. Key words: acute migraine treatment, evidence-based medicine, treatment guidelines, triptans, ergotamine, neuromodulation.

Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use.

BACKGROUND: Heavy menstrual bleeding and pain are common reasons women discontinue intrauterine device (IUD) use. Copper IUD (Cu IUD) users tend to experience increased menstrual bleeding, whereas levonorgestrel IUD (LNG IUD) users tend to have irregular menstruation. Medical therapies used to reduce heavy menstrual bleeding or pain associated with Cu and LNG IUD use include non-steroidal anti-inflammatory drugs (NSAIDs), anti-fibrinolytics and paracetamol. We analysed treatment and prevention interventions separately because the expected outcomes for treatment and prevention interventions differ. We did not combine different drug classes in the analysis as they have different mechanisms of action. This is an update of a review originally on NSAIDs. The review scope has been widened to include all interventions for treatment or prevention of heavy menstrual bleeding or pain associated with IUD use. OBJECTIVES: To evaluate all randomized controlled trials (RCTs) that have assessed strategies for treatment and prevention of heavy menstrual bleeding or pain associated with IUD use, for example, pharmacotherapy and alternative therapies. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to January 2021. SELECTION CRITERIA: We included RCTs in any language that tested strategies for treatment or prevention of heavy menstrual bleeding or pain associated with IUD (Cu IUD, LNG IUD or other IUD) use. The comparison could be no intervention, placebo or another active intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. Primary outcomes were volume of menstrual blood loss, duration of menstruation and painful menstruation. We used a random-effects model in all meta-analyses. Review authors assessed the certainty of evidence using GRADE. MAIN RESULTS: This review includes 21 trials involving 3689 participants from middle- and high-income countries. Women were 18 to 45 years old and either already using an IUD or had just had one placed for contraception. The included trials examined NSAIDs and other interventions. Eleven were treatment trials, of these seven were on users of the Cu IUD, one on LNG IUD and three on an unknown type. Ten were prevention trials, six focused on Cu IUD users, and four on LNG IUD users. Sixteen trials had high risk of detection bias due to subjective assessment of pain and bleeding. Treatment of heavy menstrual bleeding Cu IUD Vitamin B1 resulted in fewer pads used per day (mean difference (MD) -7.00, 95% confidence interval (CI) -8.50 to -5.50) and fewer bleeding days (MD -2.00, 95% CI -2.38 to -1.62; 1 trial; 110 women; low-certainty evidence) compared to placebo. The evidence is very uncertain about the effect of naproxen on the volume of menstruation compared to placebo (odds ratio (OR) 0.09, 95% CI 0.00 to 1.78; 1 trial, 40 women; very low-certainty evidence). Treatment with mefenamic acid resulted in less volume of blood loss compared to tranexamic acid (MD -64.26, 95% CI -105.65 to -22.87; 1 trial, 94 women; low-certainty evidence). However, there was no difference in duration of bleeding with treatment of mefenamic acid or tranexamic acid (MD 0.08 days, 95% CI -0.27 to 0.42, 2 trials, 152 women; low-certainty evidence). LNG IUD The use of ulipristal acetate in LNG IUD may not reduce the number of bleeding days in 90 days in comparison to placebo (MD -9.30 days, 95% CI -26.76 to 8.16; 1 trial, 24 women; low-certainty evidence). Unknown IUD type Mefenamic acid may not reduce volume of bleeding compared to Vitex agnus measured by pictorial blood assessment chart (MD -2.40, 95% CI -13.77 to 8.97; 1 trial; 84 women; low-certainty evidence). Treatment of pain Cu IUD Treatment with tranexamic acid and sodium diclofenac may result in little or no difference in the occurrence of pain (OR 1.00, 95% CI 0.06 to 17.25; 1 trial, 38 women; very low-certainty evidence). Unknown IUD type Naproxen may reduce pain (MD 4.10, 95% CI 0.91 to 7.29; 1 trial, 33 women; low-certainty evidence). Prevention of heavy menstrual bleeding Cu IUD We found very low-certainty evidence that tolfenamic acid may prevent heavy bleeding compared to placebo (OR 0.54, 95% CI 0.34 to 0.85; 1 trial, 310 women). There was no difference between ibuprofen and placebo in blood volume reduction (MD -14.11, 95% CI -36.04 to 7.82) and duration of bleeding (MD -0.2 days, 95% CI -1.40 to 1.0; 1 trial, 28 women, low-certainty evidence). Aspirin may not prevent heavy bleeding in comparison to paracetamol (MD -0.30, 95% CI -26.16 to 25.56; 1 trial, 20 women; very low-certainty evidence). LNG IUD Ulipristal acetate may increase the percentage of bleeding days compared to placebo (MD 9.50, 95% CI 1.48 to 17.52; 1 trial, 118 women; low-certainty evidence). There were insufficient data for analysis in a single trial comparing mifepristone and vitamin B. There were insufficient data for analysis in the single trial comparing tranexamic acid and mefenamic acid and in another trial comparing naproxen with estradiol. Prevention of pain Cu IUD There was low-certainty evidence that tolfenamic acid may not be effective to prevent painful menstruation compared to placebo (OR 0.71, 95% CI 0.44 to 1.14; 1 trial, 310 women). Ibuprofen may not reduce menstrual cramps compared to placebo (OR 1.00, 95% CI 0.11 to 8.95; 1 trial, 20 women, low-certainty evidence). AUTHORS' CONCLUSIONS: Findings from this review should be interpreted with caution due to low- and very low-certainty evidence. Included trials were limited; the majority of the evidence was derived from single trials with few participants. Further research requires larger trials and improved trial reporting. The use of vitamin B1 and mefenamic acid to treat heavy menstruation and tolfenamic acid to prevent heavy menstruation associated with Cu IUD should be investigated. More trials are needed to generate evidence for the treatment and prevention of heavy and painful menstruation associated with LNG IUD.

[A prospective randomized controlled study on the effects of compound analgesia in ultra-pulsed fractional carbon dioxide laser treatment of post-burn hypertrophic scars in children].

Objective: To investigate the effects of compound analgesia on ultra-pulsed fractional carbon dioxide laser (UFCL) treatment of post-burn hypertrophic s in children. Methods: A prospective randomized controlled study was conducted. From April 2018 to March 2020, 169 pediatric patients with post-burn hypertrophic s admitted to the First Affiliated Hospital of Air Force Medical University were randomly divided into general anesthesia alone group (39 cases, 19 males and 20 females, aged 35 (21, 48) months), general anesthesia+lidocaine group (41 cases, 23 males and 18 females, aged 42 (22, 68) months), general anesthesia+ibuprofen suppository group (41 cases, 25 males and 16 females, aged 38 (26, 52) months), and three-drug combination group with general anesthesia + lidocaine+ibuprofen suppository (48 cases, 25 males and 23 females, aged 42 (25, 60) months), and the pediatric patients in each group were treated with corresponding analgesic regimens when UFCL was used to treat s, and the pediatric patients were given comprehensive care throughout the treatment process. The pain degree of pediatric patients scar was evaluated by facial expression,legs,activity,cry,and consolability (FLACC) of children's pain behavior scale at 0 (immediately), 1, 2, and 4 h after awakening from the first anesthesia, respectively. At 4 h after awakening from the first anesthesia of postoperative pain assessment, the self-made analgesia satisfaction questionnaire was used to evaluate the satisfaction for the analgesic effect of the pediatric patients or their families, and the satisfaction rate was calculated. Within 2 h after the first operation, the occurrences of adverse reactions of the pediatric patients, such as nausea and vomiting, headache, dizziness, drowsiness, etc, were observed and recorded. Before the first treatment and 1 month after the last treatment, the Vancouver scar scale (VSS) was used to evaluate the pediatric patients scar, and the difference value between the two was calculated. Data were statistically analyzed with least significant difference test, Kruskal-Wallis H test, chi-square test and Fisher's exact probability test. Results: At 0 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group (P<0.01). The FLACC scores of the pediatric patients in anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than that in general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 1 and 2 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were both significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 4 h after awakening from the first anesthesia, the FLACC scores of the pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01). At 4 h after awakening from the first anesthesia, the satisfactions rate with the analgesic effect in the four groups of pediatric patients or their families were 79.49% (31/39), 85.37% (35/41), 87.80% (36/41), and 97.92% (47/48), respectively. The satisfaction rate of the pediatric patients in three-drug combination group was significantly higher than those in general anesthesia alone group, general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group. Within 2 h after the first operation, there was no significant difference in the overall comparison of adverse reactions such as nausea and vomiting, headache, dizziness, and drowsiness of pediatric patients among the 4 groups (P>0.05). The VSS scores of pediatric patients before the first treatment, 1 month after the last treatment, and and the difference value between the two in the 4 groups were not significantly different (P>0.05). Conclusions: Three-drug combination for analgesia has a good effect in the treatment of hypertrophic scars after burn in pediatric patients with UFCL. Pediatric patients or their families are highly satisfied with the effect, and the treatment effect and incidence of adverse reactions are similar to other analgesic regimens, so it is recommended to be promoted in clinical practice.

The Effects of Ibuprofen, Naproxen and Diclofenac on cell Apoptosis, Cell Proliferation and Histology Changes in Human Cholangiocarcinoma Cell Lines.

OBJECTIVE: To examine the effects of ibuprofen, naproxen and diclofenac, non-steroidal anti-inflammatory drugs (NSAIDs) on cell proliferation activity of the human CCA cell lines. METHODS: KKU-M139 and KKU-213B cell lines were used in this study. The cell viability was assessed by the MTT assay. Lipid synthesis determined by Oil red O staining and colorimetric assay. An inverted phase-contrast light microscope was used to investigate the histological change of the cells. Caspases 3/7 activity and AnnexinV/PI were used to assess apoptosis by multiple microplate reader. RESULTS: The results showed that ibuprofen, naproxen and diclofenac suppressed the viability of the KKU-M139 and KKU-213B cells in a dose-dependent manner, as measured especially diclofenac. However, these three NSAIDs slightly decreased lipid synthesis determined by Oil red O staining and colorimetric assay. The histological change observations showed the shrinking cell and become star-shaped in high dose treated groups. Interestingly, these NSAIDs exhibited in both of KKU-M139 and KKU-213B cell lines, the diclofenac-treated cells had the most injury cells. The cells exhibited cell injury features. In addition, the detection of caspase 3/7 and AnnexinV/PI in this investigation revealed early cell apoptotic characteristics. CONCLUSION: These finding suggest that ibuprofen, naproxen and diclofenac suppress cell viability. The results reveal that ibuprofen, naproxen and diclofenac, which induce the histological change and apoptosis. This study indicates that these NSAIDs may be used as an anti-proliferation agent for the treatment of CCA in the future.

Effects of Modified Wenjing Decoction Combined with Online Publicity and Education on the Treatment of Primary Dysmenorrhea of Cold Coagulation and Blood Stasis.

OBJECTIVE: To explore the effects of modified Wenjing decoction combined with online publicity and education on the treatment of primary dysmenorrhea of cold coagulation and blood stasis. METHODS: The materials of 111 patients with primary dysmenorrhea of cold coagulation and blood stasis in the outpatient department (January 2019-June 2021) were collected to conduct the retrospective study. The 111 patients were randomized into treatment group (n = 59) and control group (n = 52). The control group received online publicity and education and conventional treatment, and the treatment group received online publicity and education and modified Wenjing decoction. The patients in the two groups were continuously treated for three menstrual cycles. The treatment effects, the dosage of analgesics, the scores of associated symptoms before and after treatment, and other indexes were compared between the two groups. RESULTS: The differences in the efficacy on abdominal pain were statistically significant between the two groups (P < 0.05). Compared with the control group, the treatment group had lower scores of associated symptoms after treatment (p < 0.5). After the treatment of three menstrual cycles, 54 patients in the treatment group stopped taking ibuprofen, and the average ibuprofen dosage of the other 5 patients was (0.24 ± 0.16)g. The 52 patients in the control group still needed to take ibuprofen, and the mean dosage was (0.51 ± 0.05)g. The differences in the ibuprofen dosage between the two groups had remarkable difference (P < 0.001). CONCLUSION: Modified Wenjing decoction combined with online publicity and education can obviously improve the clinical symptoms of the patients with primary dysmenorrhea of cold coagulation and blood stasis and reduce the dosage of analgesics. It is worth promoting and applying in practice.

NSAID chronotherapy after impacted third molar extraction: a randomized controlled trial.

OBJECTIVES: Postoperative pain management impacts patients' quality of life and morbidity. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are widely used for this following a 3-doses-per-day regime. However, pain and inflammation follow a circadian rhythm, and animal models assessing the scheduling of NSAID administration (e.g., chronotherapy) have shown that while their use during the active phase of the day enhances postoperative recovery, their administration during the resting phase could have detrimental effects. This observation has led us to hypothesize that night administration of NSAID might be unnecessary in post-surgical scenarios. Therefore, a randomized clinical trial was conducted to test this hypothesis in surgical third molar extractions. MATERIALS AND METHODS: Seventy (18-35 years) healthy participants requiring surgical removal of impacted lower third molars were recruited and randomized into a double-blind placebo-controlled study. For three days postoperatively, the treatment group (n = 33) received ibuprofen (400 mg) at 8 AM, 1 PM, and a placebo at 8 PM, while the control group (n = 37) received ibuprofen (400 mg) at 8 AM, 1 PM, and 8 PM. Pain severity was assessed by visual analog scale (VAS) and healing indicators including facial swelling, mouth opening, and C-reactive protein blood levels were also measured. RESULTS: Pain VAS measures showed a circadian variation peaking at night. Also, no significant differences were observed between the two groups of the study in terms of postoperative pain scores (estimate: 0.50, 95% CI = [- 0.38, 1.39]) or any other healing indicator. CONCLUSIONS: Postoperative pain follows a circadian rhythm. Moreover, night administration of ibuprofen might not provide any significant benefits in terms of pain management and control of inflammation, and two doses during the day only could be sufficient for pain management after surgical interventions. KNOWLEDGE TRANSFER STATEMENT: Even though this study cannot rule out the possibility that a reduced regime is different than a standard regime, nocturnal doses of ibuprofen seem to have no clinical significance in the short term, and the results of this study provide evidence in favor of reducing ibuprofen administration from three doses to two doses only after third molar surgery.

A prospective randomized controlled study on the effects of compound analgesia in ultra-pulsed fractional carbon dioxide laser treatment of post-burn hypertrophic scars in children / 中华烧伤杂志

Objective: To investigate the effects of compound analgesia on ultra-pulsed fractional carbon dioxide laser (UFCL) treatment of post-burn hypertrophic s in children. Methods: A prospective randomized controlled study was conducted. From April 2018 to March 2020, 169 pediatric patients with post-burn hypertrophic s admitted to the First Affiliated Hospital of Air Force Medical University were randomly divided into general anesthesia alone group (39 cases, 19 males and 20 females, aged 35 (21, 48) months), general anesthesia+lidocaine group (41 cases, 23 males and 18 females, aged 42 (22, 68) months), general anesthesia+ibuprofen suppository group (41 cases, 25 males and 16 females, aged 38 (26, 52) months), and three-drug combination group with general anesthesia + lidocaine+ibuprofen suppository (48 cases, 25 males and 23 females, aged 42 (25, 60) months), and the pediatric patients in each group were treated with corresponding analgesic regimens when UFCL was used to treat s, and the pediatric patients were given comprehensive care throughout the treatment process. The pain degree of pediatric patients scar was evaluated by facial expression,legs,activity,cry,and consolability (FLACC) of children's pain behavior scale at 0 (immediately), 1, 2, and 4 h after awakening from the first anesthesia, respectively. At 4 h after awakening from the first anesthesia of postoperative pain assessment, the self-made analgesia satisfaction questionnaire was used to evaluate the satisfaction for the analgesic effect of the pediatric patients or their families, and the satisfaction rate was calculated. Within 2 h after the first operation, the occurrences of adverse reactions of the pediatric patients, such as nausea and vomiting, headache, dizziness, drowsiness, etc, were observed and recorded. Before the first treatment and 1 month after the last treatment, the Vancouver scar scale (VSS) was used to evaluate the pediatric patients scar, and the difference value between the two was calculated. Data were statistically analyzed with least significant difference test, Kruskal-Wallis H test, chi-square test and Fisher's exact probability test. Results: At 0 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group (P<0.01). The FLACC scores of the pediatric patients in anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than that in general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 1 and 2 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were both significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 4 h after awakening from the first anesthesia, the FLACC scores of the pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01). At 4 h after awakening from the first anesthesia, the satisfactions rate with the analgesic effect in the four groups of pediatric patients or their families were 79.49% (31/39), 85.37% (35/41), 87.80% (36/41), and 97.92% (47/48), respectively. The satisfaction rate of the pediatric patients in three-drug combination group was significantly higher than those in general anesthesia alone group, general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group. Within 2 h after the first operation, there was no significant difference in the overall comparison of adverse reactions such as nausea and vomiting, headache, dizziness, and drowsiness of pediatric patients among the 4 groups (P>0.05). The VSS scores of pediatric patients before the first treatment, 1 month after the last treatment, and and the difference value between the two in the 4 groups were not significantly different (P>0.05). Conclusions: Three-drug combination for analgesia has a good effect in the treatment of hypertrophic scars after burn in pediatric patients with UFCL. Pediatric patients or their families are highly satisfied with the effect, and the treatment effect and incidence of adverse reactions are similar to other analgesic regimens, so it is recommended to be promoted in clinical practice.

Effects of ibuprofen administration timing on oral surgery pain: A randomized clinical trial.

OBJECTIVE: This study aimed to compare the analgesic effect of ibuprofen 400 mg given 30 min before or immediately after third molars surgery under local anaesthesia. MATERIALS AND METHODS: The single-centre, randomized, split-mouth, triple-blind, clinical trial involved 38 outpatients, for a total of 76 bilateral symmetrical fully bone impacted mandibular third molars. Each patient was undergone to separate surgical sessions for the right and left side, and ibuprofen was randomly administered 30 min before or immediately after the intervention. Study participants recorded pain intensity using Numerical Rating Scale-11, the timing of rescue therapy intake and overall tablets consumption over 3 days. RESULTS: The overall pain intensity score was lower in the group receiving ibuprofen immediately after (3.13 ± 2.46) than before (3.58 ± 2.40) surgery, with statistically significant differences only on the second and third days. The mean time to the first using rescue therapy was longer in the postoperative (598.33 ± 422.62 min) than in the preoperative (406.25 ± 149.79 min) analgesic treatment group (p = .123). The number of supplemented ibuprofen tablets did not differ (p = .530) between both groups. CONCLUSIONS: Within the limits of the present study, ibuprofen administration immediately after surgery seemed to be more effective than preoperative administration.

Preemptive analgesic effectiveness of single dose intravenous ibuprofen in infants undergoing cleft palate repair: a randomized controlled trial.

BACKGROUND: Correction surgery for cleft palate is recommended between 9 and 18 months of age. Patients suffer from acute pain after palatoplasty. Clinicians are hesitant to use opioids for analgesia concerning the potential high risk of respiratory adverse events. Intravenous ibuprofen perhaps be a suitable adjuvant to pain relief. We try to assess whether preoperative administration of intravenous ibuprofen can decrease opioid requirements following cleft palate repair in infants. METHODS: This single center prospective randomized clinical trial was performed from February to April 2021 at Department of Anesthesiology in Shanghai Children's Medical Center. Forty patients ASA I-II, aged 9-24 months with isolated cleft palate and undergoing palatoplasty were randomized in a 1:1 ratio to receive either a single dose of 10 mg/kg ibuprofen intravenously or normal saline at induction. Children and infants postoperative pain scale (CHIPPS) was used for pain assessment. Those patients CHIPPS pain score equal or higher than 4 received analgesic rescue with titrating intravenous fentanyl 0.5 µg/kg and repeated in 10 min if required. The primary outcome was the amount of postoperative fentanyl used for rescue analgesia in postanesthesia care unit (PACU). RESULTS: Patients (n = 20 in each group) in IV-Ibuprofen group required less postoperative fentanyl than those in placebo group (p<0.001). There was no significant difference between two groups in first rescue analgesia time (p = 0.079) and surgical blood loss (p = 0.194). No incidence of obvious adverse events had been found within the first 24 h after surgery in both groups. CONCLUSIONS: Preemptive intravenous administration ibuprofen 10 mg/kg at induction had a significant opioid sparing effect in early postoperative period without obvious adverse effects in infants undergoing palatoplasty. TRIAL REGISTRATION: CHICTR, CTR2100043718, 27/02/2021 http://www.chictr.org.cn/showproj.aspx?proj=122187.

Pharmacological Means of Pain Control during Separator Placement: A Systematic Review.

AIM: To assess the effectiveness of adjuvant analgesics/anesthetics in pain control after separator placement compared with no medication. BACKGROUND: Separator placement to create space for cementing bands is the first clinical procedure done in orthodontics. Pain in this stage can negatively affect patient compliance and trust in the clinician. To date, there is no universally accepted regimen for pain control. MATERIALS AND METHODS: Electronic databases of PubMed, Scopus, and Web of Science were searched. One hundred and thirty-two potentially relevant studies were found. A total of eight randomized clinical trials including 642 subjects were selected. Data were extracted into customized forms, and selected studies were assessed for risk of bias using the Joanna Briggs Institute. RESULTS: Results showed the use of analgesics led to lower reported pain scores at almost all time intervals. NSAIDs resulted in a statistically significant reduction in pain compared to a control group. CONCLUSION: According to the available literature, the use of analgesics is effective in controlling orthodontic pain due to separators. Acetaminophen and ibuprofen show a stable analgesic effect. CLINICAL IMPLICATION: Acetaminophen 650 mg or ibuprofen 400 mg taken 1 hour prior to separator placement can reduce pain associated with the procedure.

Pharmacological and Non-Pharmacological Methods of Postoperative Pain Control Following Oral and Maxillofacial Surgery: A Scoping Review.

PURPOSE: To conduct a scoping review regarding current pharmacological and non-pharmacological methods of postoperative pain control following oral and maxillofacial surgery. MATERIALS AND METHODS: PubMed was used to conduct research for this study. Identification criteria included surgery: patients undergoing the extraction of third molars; therapy: pharmacological or non-pharmacological methods; and outcomes: postoperative pain control. The search included full-text RCTs published after October 13, 2014, that were electronically accessible on PubMed and in the English language. After assessing quality, a scoping review was performed. RESULTS: Thirty-five RCTs were evaluated, which included a total of 3,791 subjects. The studies evaluated patients' postoperative pain by either utilizing a visual analogue scale (VAS), measuring the time between surgery and when rescue analgesics were used, measuring the amount of rescue analgesics used, or by distributing questionnaires. CONCLUSION: COX-2 inhibitors may provide greater analgesic effects compared to traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Additionally, although the supplementation of an opioid analgesic to a NSAID regimen provides an increase in pain control, it does not further reduce pain levels in a patient alternating between ibuprofen and acetaminophen. Other methods of postoperative pain control mentioned in this review should be further explored in studies that contain larger sample sizes and that evaluate side effects of the treatment.

Comparative efficacy and dysmenorrhea score of 6 object-separated moxibustions for the treatment of Chinese patients with dysmenorrhea: A systematic review and network meta-analysis.

BACKGROUND: Primary dysmenorrhea (PD), one of the most common diseases in women, is known to be effective with object-separated moxibustion. However, because there is no large sample size for comparison, it is difficult to choose the best method for the clinical treatment of these different treatments. Therefore, our aim was to compare and rank different moxibustion methods to determine the most effective treatment method for PD. MATERIALS AND METHODS: A systematic search was carried out in PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature, to identify the randomized controlled trials (RCTs) investigated the object-separated moxibustion is associated with dysmenorrhea, as well as we also manually checked the bibliographies of eligible studies and topic-related reviews, RCTs from their inception to May 1, 2020. Three investigators read the citations and excluded quasi-randomized trials and trials that were incomplete. We extracted data following a predefined hierarchy. We assessed the studies' risk of bias in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The primary outcomes were efficacy (response rate) and dysmenorrhea scores. We estimated the summary odds ratio (OR) and mean difference (MD) using pairwise and network meta-analyses with random effects. STATA software version 16.0, ADDIS software version 1.16.5, and R software version 3.6.1 were used to statistically analyze all data. RESULTS: Fifty-six RCTs with 5550 patients were included, comparing 6 object-separated moxibustion therapies with acupuncture or oral medicine. All moxibustions were more effective than ibuprofen, with OR ranging between 6.75 (95%CI: 3.58 to 13.22) for moxibustion at the navel. For relieving pain which uses dysmenorrhea score to evaluate, mild moxibustion (MD = -1.42, -4.24 to 0.85) was more effective than others. A total of 24 (42.8%) of 56 trials were rated as having a high risk of bias, 31(55.4%) as moderate, and 1(1.8%) as low, and the certainty of the evidence was moderate. CONCLUSIONS: Mild moxibustion cannot only effectively treat PD but also relieve pain in comparison with ibuprofen. Although GRADE evidence indicate low to moderate for most comparisons, mild moxibustion seems to be an advisable option for PD treatment to relieve symptoms.

Assessment of pharmacological activities of Lygodium microphyllum Cav. leaves in the management of pain, inflammation, pyrexia, diarrhea, and helminths: In vivo, in vitro and in silico approaches.

Lygodium microphyllum Cav. (Family: Lygodiaceae) is a perennial, snake fern and an invasive weed in Florida and also known as old world climbing fern. This study is intended to evaluate the antipyretic, analgesic, anti-inflammatory, antidiarrheal and anthelmintic activity of methanol extract of Lygodium microphyllum Cav. leaves (MELM) by in vivo, in vitro and in silico approaches. In addition, Biovia, PyRx autoDock Vina, UCSF Chimera have been applied to investigate the docking study in order to evaluate the binding interaction and an online tool was used to explore the ADME/T properties of selected bioactive compounds. In acetic acid induced writhing study, MELM inhibited 44.28% and 56.61% of writhes at 200 and 400 (mg/kg) respectively compared to standard drug Diclofenac-Na (10 mg/kg) (74.42% inhibition). In anti-inflammatory experiment by formalin triggered licking method, MELM caused significant (p < 0.05) inhibition of licking in both early phase (42.97%, 63.30%) and late phase (43.35%, 63.03%) at the doses of 200 and 400 mg/kg respectively, whereas reference drug Ibuprofen inhibited paw licking 77.18% in early phase and 76.86% in late phase. MELM also showed promising antipyretic potential where the maximum reduction of fever was produced by MELM 400 mg/kg whose fever lowering capacity is close to the prescribe drug Indomethacin 4 mg/kg, i.p. In Castor oil triggered diarrhea method, MELM delayed the onset time of diarrhea, continuous persistence of wet feces, and decreased the weight of wet feces remarkably. Defection inhibition was achieved 27.56% and 51.72%, for MELM 200 and at 400 (mg/kg) respectively while loperamide 2 (mg/kg) yields 55.17% inhibition of the diarrheal defecation. In anthelmintic bioassay, MELM took 5.83 ± 0.83 and 41.67 ± 1.78 min respectively for paralyzing and death compared to standard drug albendazole; (paralysis time 4.00 ± 0.73 min and death time 31,00 ± 1.71 min). Isoeleutherol, isoquercetin and quercetin were found prominent in molecular docking study and ADME/T analysis verified their drug likeliness. The research validates the moderate analgesic, anti-inflammatory, and remarkable antipyretic, antidiarrheal, anthelmintic activities of the plant extract which can be used an alternative source of novel therapeutics.

Efficacy of Intravenous Paracetamol and Ibuprofen on Postoperative Pain and Morphine Consumption in Lumbar Disc Surgery: Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVES: Effective postoperative pain management after lumbar disc surgery reduces complications and improves postoperative care. The purpose of this prospective, randomized, double-blind, placebo-controlled clinical study is to evaluate the effects of IV paracetamol and ibuprofen on postoperative pain, morphine consumption and side effects of morphine in patients who underwent lumbar disc surgery. MATERIALS AND METHODS: Seventy-five patients aged 18-85 years scheduled for lumbar disk surgery with a single level laminectomy included in this study. All patients received morphine with an IV patient-controlled analgesia device during the first postoperative 24hour. The patients were divided randomly and double-blinded into three groups (control, paracetamol and ibuprofen). The demographic characteristics and procedure data, VAS score, cumulative morphine consumption, opioid-related side effects were recorded. RESULTS: There was no significant difference regarding to demographic characteristics, comorbidities, and durations of anesthesia and surgery. There was a significant difference between all groups regarding to total morphine consumption (P<0.001). IV ibuprofen significantly reduced the total morphine consumption in comparison with control and paracetamol (P<0.001). Repeated measures ANOVA showed in all periods of the study that VAS score was significantly lower in ibuprofen (P<0.001), but not in paracetamol (P=0.394) in comparison with control. There was no difference between groups regarding postoperative heart rate, mean arterial pressure, nausea-vomiting, pruritus and urinary retention. CONCLUSIONS: This study showed that pain scores and morphine consumption, but not the side effects of patient-controlled analgesia during 24hours after the lumbar disk surgery, were significantly reduced by IV ibuprofen as a supplemental analgesic when compared with controls and paracetamols.