Mean Pain Intensity Difference Research Articles

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.

The Effect of Aromatherapy with Citrus aurantium Aroma on Pain after Orthopedic Surgery: A Randomized Clinical Trial.

Postoperative pain is one of the most common physiological and psychological stress in patients that disrupts body function and can endanger patients' health. This study aims to determine the effect of aromatherapy with Citrus aurantium essential on pain after orthopedic surgery. This randomized clinical trial was performed on 60 candidates for orthopedic surgery. Patients were selected through convenience sampling and divided into intervention and control groups through randomized block allocation. If the visual analogue scale (VAS) score was above 3, patients in the intervention group received aromatherapy with C. aurantium essential and the patients in the control group received a placebo (almond oil). VAS was used to measure pain. Data analysis was performed using independent t test, paired t test, and analysis of variance with repeated measures using SPSS software version 13. Mean (SD) of pain intensity after intervention in experimental and control groups within 4, 8, and 12 hours after surgery was 7.30 (1.23) vs. 7.90 (0.99), 5.30 (0.98) versus 5.53 (0.68) and 2.53 (0.9) vs. 3.60 (0.77) respectively. The findings indicated that there was a significant difference in mean pain intensity between the experimental and control groups at 4 and 12 hours after surgery. Use of analysis of variance with repeated measures test with taking into account the interaction of time and group also showed a significant difference in mean pain intensity between the two experimental and control groups. Aromatherapy with Citrus aurantium essential can be effective in reducing mild to moderate pain after orthopedic surgery. Further studies are recommended to confirm this finding.

The Analgetic Efficacy of Pterygopalatine Blockade for Pain Treatment in Adults: a Systematic Review and Meta-Analysis

Background. The use of regional blockades for the purpose of analgesia is widely used in all fields of medicine, however, the analgesic efficacy of the pterygopalatine blockade, as an independent method of treating pain of various genesis, has not been studied enough. Therefore, there is a need to analyze the results of clinical trials to evaluate the analgesic efficacy of the pterygopalatine blockade as an independent method of anesthesia.Objective — to investigate the analgesic effect of pterygopalatine blockade as a monotherapy in patients with pain of various origins of oculotemporal area, conducting a meta-analysis of published results of randomized clinical trials.Methods. The methodology involved a systematic literature search by means of PubMed, MEDLINE, EMBASE, and Cochrane Library search engines. The search covered the period of the past 10 years and had the following criteria: a double-blind, randomized, controlled study of the use of pterygopalatine blockade with a local anesthetic versus placebo. For each included study, a standardized magnitude of the analgesic effect of pterygopalatine blockade compared to placebo was calculated, with pain assessing in 15, 30, and 60 minutes after the blockade was performed. Meta-analyses were conducted for each endpoint. Meta-analysis was performed using Stata 11.0 application programs ((The Cochrane Collaboration, Oxford, United Kingdom).Results. Five randomized controlled trials involving 269 patients met the inclusion criteria, and involved analyzing the pterygopalatine blockade with local anesthetic (n=140) against placebo (n=129). In 15 minutes after pterygopalatine blockade was performed, the difference in mean pain intensity compared to the control group was -2.5 points, the mean level was lower in the pterygopalatine blockade group, MD=-2.5 [95% CI -3.7; -1.7]. After 30 minutes: -2.7 points, MD=-2.7 [95% CI -4.5; -1.5], after 60 minutes: -1.7 points, MD=-1.7 [95% CI -4.0; -0.5]. The relative risk of adverse effects, such as nasopharyngeal symptoms, after performing a pterygopalatine blockade with a local anesthetic accounted for (RR =1.31 [95% CI 0.5–3.04]). In this regard, the incidence of complications and their variants that can be caused by pterygopalatine blockade is a matter for further clinical research.Conclusion. The results obtained in the meta-analysis testify to the analgesic effect of the pterygopalatine blockade as a monotherapy in patients with pain of different origins oculotemporal area in 15, 30, and 60 minutes after its performance. These data may be relevant when choosing a method for first-line anesthetic management of pain syndrome of oculotemporal area.

Pre-emptive Analgesic Efficacy of Single-Dose Transdermal Ketoprofen and Diclofenac Patches in Post-operative Pain Management Following Open Treatment of Mandibular Fractures: A Randomized Controlled Study.

Introduction: The present study was deliberated to assess the pre-emptive analgesic efficacy of diclofenac sodium and ketoprofen transdermal patches following open treatment of mandibular fractures.Methods: The present prospective, triple-blind, randomized controlled clinical study was carried out on 50 male patients with a mean age of 30-31 years having bifocal mandibular fractures. The subjects were assigned 1:1 to two groups; group K - ketoprofen group and group D - diclofenac sodium group. Patches were applied according to the group allocation one hour before induction. In the immediate post-operative (PO) phase, pain intensity was recorded using a 10-point Visual analog Scale at 2, 4, 8, 12, and 24 hourly. Statistical analysis was performed using descriptive and inferential statistics using SPSS 27.0 version (IBM SPSS, Armonk, NY) and GraphPad Prism 7.0 version (GraphPad Software, Inc., La Jolla, CA) and p<0.05 is considered a level of significance.Results : The present study demonstrated a statistical difference in mean pain intensity among both groups, with lower pain scores at all time intervals and fewer rescue analgesic consumption in the ketoprofen group.Conclusion: The ketoprofen transdermal patch was found to be superior in comparison to the diclofenac patch in terms of providing optimal post-operative analgesia with a reduced requirement for post-operative rescue analgesics and minimal adverse events.

Efficacy and safety of fixed-dose combination of drotaverine hydrochloride (80mg) and paracetamol (500mg) in amelioration of abdominal pain in acute infectious gastroenteritis: A randomized controlled trial.

This randomized controlled trial was undertaken to assess efficacy and safety of fixed-dose combination of drotaverine hydrochloride (80mg) and paracetamol (PCM) (500mg). This was performed by comparison of mean pain intensity difference, total pain relief at 2h, onset of pain relief, decrease in number of pain episodes, global improvement, and adverse effects. A randomized double-blind controlled trial for adults between 18 and 59years of either gender with acute infectious diarrhea (≥3 unformed, watery, or soft stools with symptoms at least within the last 24h preceding randomization with duration of illness not more than 72h) with moderate-to-severe abdominal pain. Participants were treated with either a fixed-dose combination of oral drotaverine hydrochloride (80mg) and PCM (500mg) or oral PCM (500mg) three times a day for 3days. Of 252 (126 in each group) participants, all received at least one dose of medication. Two hundred forty-two completed the study. Mean pain intensity difference at 60min after administration of study medication by Visual Analogue Scale (VAS) and total pain relief at 2h using both VAS and Verbal Rating Scale showed statistically significant improvement in drotaverine hydrochloride (80mg) and PCM (500mg) group. The onset of pain relief was also significantly better in drotaverine hydrochloride (80mg) and PCM (500mg) group when using VAS. Fixed-dose combination of drotaverine hydrochloride (80mg) and PCM (500mg) is an effective and safe antispasmodic agent in abdominal pain associated with acute infectious gastroenteritis.

Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: a randomized, double-blind, placebo-controlled trial.

Neuropathic pain and spasticity after spinal cord injury (SCI) represent significant problems. Palmitoylethanolamide (PEA), a fatty acid amide that is produced in many cells in the body, is thought to potentiate the action of endocannabinoids and to reduce pain and inflammation. This randomized, double-blind, placebo-controlled, parallel multicenter study was performed to investigate the effect of ultramicronized PEA (PEA-um) as add-on therapy on neuropathic pain in individuals with SCI. A pain diary was completed and questionnaires were completed before and after the 12-week treatment with either placebo or PEA-um. The primary outcome measure was the change in mean neuropathic pain intensity from the 1-week baseline period to the last week of treatment measured on a numeric rating scale ranging from 0 to 10. The primary efficacy analysis was the intention to treat (baseline observation carried forward). Secondary outcomes included a per protocol analysis and effects on spasticity, evoked pain, sleep problems, anxiety, depression, and global impression of change. We randomized 73 individuals with neuropathic pain due to SCI, of which 5 had a major protocol violation, and thus 68 were included in the primary analysis. There was no difference in mean pain intensity between PEA-um and placebo treatment (P = 0.46, mean reductions in pain scores 0.4 (-0.1 to 0.9) vs 0.7 (0.2-1.2); difference of means 0.3 (-0.4 to 0.9)). There was also no effect of PEA-um as add-on therapy on spasticity, insomnia, or psychological functioning. PEA was not associated with more adverse effects than placebo.

Efficacy and safety of parecoxib/phloroglucinol combination therapy versus parecoxib monotherapy for acute renal colic: a randomized, double-blind clinical trial.

To investigate whether the addition of phloroglucinol to parecoxib could improve the efficacy in patients with acute renal colic. Patients of acute renal colic were randomly allocated to receive intravenous Parecoxib 40 mg plus placebo or Parecoxib 40 mg plus phloroglucinol 80 mg, respectively. Pain intensity was recorded using a visual analog scale (VAS) before drug administration and 5, 15, 30, 60, and 120 min after treatment start. The primary outcome was the mean pain intensity difference (PID) at each checkpoint and the effectiveness of drugs (≥ 50 % decrease in VAS score at the end checkpoint). The need for rescue analgesics and the incidence of adverse effects were considered as secondary outcome of the study. Among 236 patients enrolled in the study, 119 patients received intravenous parecoxib plus placebo and 114 patients received intravenous parecoxib plus phloroglucinol, the remaining 3 patients given up treatment. Baseline demographics were similar between two groups. There are significant differences in the PID at 15 and 30 min between two groups (P15 min = 0.011, P30 min = 0.013). Rescue analgesics were required by 17 patients (14.3 %) receiving parecoxib, 7 patients (6.1 %) receiving parecoxib plus phloroglucinol (P = 0.041). There were no differences in PID at other checkpoints between two groups, as well as in the incidence of adverse events and the drug effectiveness. Parecoxib in combination with phloroglucinol for acute renal colic has a faster action, also reduces the demand of rescue analgesics.

Postoperative Analgesia in the Jamaican Cannabis User

Background: Anecdotal reports suggest that cannabis users require increased postoperative analgesia but there is insufficient supporting data. Methods: A prospective randomized study was carried out in 73 patients undergoing elective operations. Postoperatively, all patients were assessed by a blinded investigator, who recorded pain intensity, sedation levels, mood, and hourly analgesia requirements. We calculated the mean pain intensity difference at the first postoperative hour (MPID1) and the sum of pain intensity differences (SPID1). The following end points were compared between cannabis users and non-users using SPSS 16: MPID1; SPID; patient mood; supplemental analgesia requirements and global assessment scores. Results: There were 42 cannabis users and 31 non-users. Cannabis users had significantly higher supplemental pethidine requirements (82.7 mg, SD = 3.4 vs. 51.6 mg, SD = 42.7, p = 0.003) and significantly greater MPID1 scores (1.88, SD = 1.09 vs. 1.35, SD = 1.12, p = 0.001) compared to non-users. Female cannabis users required significantly more analgesia than males (93.3 mg, SD = 45.8 vs. 78.3 mg, SD = 44.3, p = 0.025). Conclusion: Cannabis users require significantly more opioid rescue analgesia in the immediate postoperative period. Further research is needed to elucidate the precise mechanism by which this occurs.

Efficacy and Safety of Low Dose Subcutaneous Diclofenac in the Management of Acute Pain: A Randomized Double‐Blind Trial

Diclofenac is an effective and well-tolerated nonsteroidal anti-inflammatory drug (NSAID) frequently used in the treatment of acute pain. Marketed formulations for parenteral administration usually contain 75mg/3mL of diclofenac sodium, which provide limited dosing flexibility, and are usually given intramuscularly. We present a randomized, double-blind, active comparator- and placebo-controlled, parallel-group phase III multicenter study, investigating efficacy and tolerability of a new 1mL-volume formulation of diclofenac sodium (25, 50 or 75mg) containing hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer. This low-volume formulation allows subcutaneous (SC), in addition to intramuscular (IM) administration. Patients developing moderate-to-severe pain (≥50mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25mg diclofenac HPβCD (n=77), 50mg diclofenac HPβCD (n=76), 75mg diclofenac HPβCD (n=78), or placebo (n=75). Mean pain intensity difference at 1.5hours postdose (primary endpoint) was higher in all diclofenac-treated groups than placebo group. The adjusted means (95% CI) were 36.5 (31.7 to 41.2) in diclofenac 25mg group, 37.3 (32.6 to 42.1) in diclofenac 50mg group, 37.7 (33.0 to 42.4) in diclofenac 75mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50mg doses of diclofenac produced significantly greater pain relief than placebo (P<0.001 in both comparisons). Single SC doses of diclofenac HPβCD of 25 and 50mg are effective and well tolerated for relieving pain compared with placebo.

Repeat-dose steady-state pharmacokinetic evaluation of once-daily hydromorphone extended-release (OROS&amp;reg; hydromorphone ER) in patients with chronic pain

ObjectiveTo characterize the steady-state pharmacokinetic profile of hydromorphone extended-release (ER) in patients with chronic pain taking concomitant medications.MethodsThis open-label repeat-dose study enrolled 22 patients (mean age, 51.4 years; 81.8% female). All patients were receiving at least one concomitant medication; 86.4% were receiving at least two concomitant medications and 81.8% were receiving at least three. Patients receiving a stable dose of an opioid were converted to hydromorphone ER at a 5:1 ratio (morphine equivalent:hydromorphone). The dose was titrated to adequate analgesia over 3–14 days and stabilized between 8–48 mg. Oral morphine immediate-release was permitted for breakthrough pain. Area under the concentration–time curve from 0–24 hours (AUC0–24), maximum plasma concentration (Cmax), trough plasma concentration (Cmin), average plasma concentration (Cavg), and degree of fluctuation (100 × [(Cmax − Cmin) ÷ Cavg]) were calculated based on data from 14 patients.ResultsDose-normalized to 16 mg, mean pharmacokinetic parameter values were: AUC0–24, 41.1 ng · h/mL; Cmax, 2.6 ng/mL; Cmin, 1.1 ng/mL; Cavg, 1.7 ng/mL; and the degree of fluctuation was 99.6%. The pharmacokinetic profile of hydromorphone ER was linear and consistent with dose proportionality. Mean pain intensity difference scores showed statistically significant improvement from 2–21 hours after dosing. Sixteen (72.7%) patients reported at least one adverse event (AE). The most common were constipation (31.8%), headache (22.7%), and vomiting (13.6%). One patient discontinued treatment due to vomiting. No deaths, serious AEs, or unexpected AEs occurred.ConclusionThese findings replicate and extend the steady-state pharmacokinetic profile of hydromorphone ER, previously characterized in healthy volunteers, to a population of chronic pain patients taking numerous concomitant medications.

Efficacy and safety of parecoxib in the treatment of acute renal colic: a randomized clinical trial

Although non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and opioids are effective treatments for acute renal colic, they are associated with adverse events (AEs). As cyclooxygenase-2 selective NSAIDs may provide a safer alternative, we compared the efficacy and safety of parecoxib versus an nsNSAID in subjects with acute renal colic. Phase IV., multicenter, double-blind, noninferiority, active-controlled study: 338 subjects with acute renal colic were randomized to parecoxib 40 mg i.v. plus placebo (n = 174) or ketoprofen 100 mg IV plus placebo (n = 164). 338 subjects with acute renal colic were randomized to parecoxib 40 mg IV (n = 174) or ketoprofen 100 mg IV(n = 164) plus placebo. Subjects were evaluated 15, 30, 45, 60, 90 and 120 minutes after treatment start and 24 hours after discharge. Primary endpoint was the mean pain intensity difference (PID) at 30 minutes by visual analog scale (VAS) (per-protocol population). An ANCOVA model was used with treatment group, country, and baseline score as covariates. Non-inferiority of parecoxib to ketoprofen was declared if the lower bound of the 95% confidence interval (CI) for the difference between the two groups excluded the pre-established margin of 10 mm for the primary endpoint. Baseline demographics were similar. The mean (SD) mPID30 min was 33.84 (24.61) and 35.16 (26.01) for parecoxib and ketoprofen, respectively. For treatment difference (parecoxib-ketoprofen) the lower bound of the 95% CI was 6.53. The mean change from baseline in VAS 30 minutes after study medication was ~43 mm; AEs were comparable between treatments. Parecoxib is as effective as ketoprofen in the treatment of pain due to acute renal colic, is well tolerated, and has a comparable safety profile.

Fentanyl Sublingual

Fentanyl is a potent opioid with a short duration of action. Fentanyl sublingual has been formulated as a rapidly disintegrating tablet that is quickly absorbed, producing a fast onset of analgesia. In two randomized, double-blind clinical trials, fentanyl sublingual as single fixed or titrated doses reduced pain intensity during breakthrough pain episodes to a significantly greater extent than placebo in opioid-tolerant cancer patients. In a fixed-dose phase II trial and a titrated-dose phase III trial, fentanyl sublingual (as a single 400 μg dose and as titrated doses) reduced mean pain intensity difference (PID) to a significantly greater extent than placebo over the entire treatment period (up to 60 minutes), reaching statistical significance 15 minutes post-dose. In the titrated-dose study, the mean sum of PID (area under the PID vs time curve) at 30 minutes post-dose was significantly greater with fentanyl sublingual than placebo, with significant improvements in PID seen at 10 minutes maintained at 60 minutes post-dose. In the phase III study, patients receiving fentanyl sublingual were more satisfied with their treatment than patients receiving placebo (measured using the Patient Global Evaluation of Medication score), and almost half of all fentanyl sublingual recipients were satisfied or very satisfied with their treatment. Fentanyl sublingual was generally well tolerated in the two trials and most adverse events were mild to moderate in intensity.

A Randomized, Placebo‐Controlled Trial of Acetaminophen for Treatment of Migraine Headache

To evaluate the efficacy and safety of acetaminophen 1000 mg for the treatment of episodic migraine headache. While acetaminophen is commonly used to treat migraine, there have been limited published clinical trial efficacy results. Ten investigators at 13 private, ambulatory, primary care sites in the United States enrolled and treated 346 outpatient adults 18-72 years of age with migraine headache of moderate to severe intensity into a randomized, placebo-controlled, double-blind clinical trial of 6 hours duration. Each patient was randomly assigned to a single dose of study medication of acetaminophen 1000 mg (n = 177) or placebo (n = 169). The percentage of patients with a reduction in baseline headache pain intensity from severe or moderate to mild or none 2 hours after treatment and the headache pain intensity difference from baseline at 2 hours were the primary efficacy measures. Other measures of pain relief, severity differences from baseline for migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability, and percentage of patients with migraine-associated symptoms reduced to none were also assessed. Significantly (P = .001) more patients treated with acetaminophen 1000 mg reported mild to no pain after 2 hours (52.0%) compared with those treated with placebo (32.0%). The mean pain intensity difference from baseline measured at 2 hours was significantly (P < .001) greater for patients treated with acetaminophen 1000 mg (0.82) compared with those treated with placebo (0.46). A significant difference in favor of acetaminophen 1000 mg over placebo was also observed at 1 hour after treatment for the percentage of patients with mild to no pain and for mean pain intensity difference from baseline. Acetaminophen 1000 mg was significantly more effective than placebo for all but 1 (pain reduced to none at 2 hours) clinically important secondary pain relief outcomes. Mean severity changes from baseline in migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability at 2 and 6 hours were significantly (P < .001) in favor of acetaminophen over placebo; the percentage of patients with no symptoms at 2 and 6 hours statistically significantly favored acetaminophen in 6 of 8 comparisons. Adverse events, overall, and specifically for nausea, were reported more frequently in the placebo group. Acetaminophen 1000 mg, a nonprescription drug, is an effective and well-tolerated treatment for episodic and moderate migraine headache. In addition, acetaminophen generally provided a beneficial effect on associated symptoms of migraine including nausea, photophobia, phonophobia, and functional disability.

Analgesic efficacy of the cyclooxygenase-inhibiting nitric oxide donor AZD3582 in postoperative dental pain: Comparison with naproxen and rofecoxib in two randomized, double-blind, placebo-controlled studies

Abstract Objective: This study assessed the analgesic efficacy of single doses of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate (AZD3582) in acute postoperative dental pain after the removal of an impacted mandibular third molar (ie, wisdom tooth). Methods: Two randomized, placebo-controlled, double-blind studies were performed. In a dose-finding study, 242 patients were randomized to AZD3582 375, 750, 1500, or 2250 mg (n = 41, 37, 42, and 41, respectively); naproxen 500 mg (n = 39); or placebo (n = 42). In a comparator study, 282 patients were randomized to AZD3582 500 mg (n = 78) or 750 mg (n = 83), rofecoxib 50 mg (n = 80), or placebo (n = 41). Primary outcomes included to rescue medication, to pain relief, and mean pain intensity difference (MPID), as well as safety profile. Pain was rated on a visual analog scale. Results: In the dose-finding study, 52% (126/242) were women; the mean (SD) age was 25.1 (4) years, mean weight was 69.0 kg, and the mean (SD) body mass index (BMI) was 23.7 (3) kg/m 2 . In the comparator study, 58% (164/282) were women; the mean (SD) age was 27 (6.4) years, mean weight was 71 kg, and mean (SD) BMI was 24.2 (3) kg/m 2 . In the dose-finding study, the AZD3582 750-, 1500-, and 2250-mg groups were superior to placebo in the primary variables time to rescue medication (0–8 hours) (hazard ratios [HRs] [95% CIs], 0.17 [0.07–0.42], P P P P P P P P P P P P = NS, P = 0.003, P P P P = 0.02), and MPID (11.9 [4.2–19.5], P = 0.002). However, inferiority of AZD3582 to rofecoxib for MPID could not be excluded (tolerance limit of 10 mm; P = NS for noninferiority testing). The median times to confirmed perceptible pain relief were 45 minutes for AZD3582 500 mg, 40 minutes for 750 mg, and 37 minutes for rofecoxib. The median times tofirst rescue medication were 218 minutes for AZD3582 500 mg, 365 minutes for 750 mg, 635 minutes for rofecoxib, and 90 minutes for placebo. Overall, AZD3582 was well tolerated. However, an effect on orthostatic blood pressure could not be excluded because there seemed to be more subjects with dizziness and orthostatic blood pressure reduction who were administered AZD3582 ≥750 mg. The proportions of patients with vertigo and decreased orthostatic blood pressure each group were as follows: AZD3582 500 mg, 6%; AZD3582 750 mg, 12%; rofecoxib, 3%; and placebo, 5%. Conclusions: AZD3582 750 mg had similar analgesic efficacy as equimolar doses of naproxen, but noninferiority to rofecoxib was not demonstrated.

Analgesic efficacy of the cyclooxygenase-inhibiting nitric oxide donor AZD3582 in postoperative dental pain: Comparison with naproxen and rofecoxib in two randomized, double-blind, placebo-controlled studies

Objective: This study assessed the analgesic efficacy of single doses of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate (AZD3582) in acute postoperative dental pain after the removal of an impacted mandibular third molar (ie, wisdom tooth). Methods: Two randomized, placebo-controlled, double-blind studies were performed. In a dose-finding study, 242 patients were randomized to AZD3582 375, 750, 1500, or 2250 mg (n = 41, 37, 42, and 41, respectively); naproxen 500 mg (n = 39); or placebo (n = 42). In a comparator study, 282 patients were randomized to AZD3582 500 mg (n = 78) or 750 mg (n = 83), rofecoxib 50 mg (n = 80), or placebo (n = 41). Primary outcomes included time to rescue medication, time to pain relief, and mean pain intensity difference (MPID), as well as safety profile. Pain was rated on a visual analog scale. Results: In the dose-finding study, 52% (126/242) were women; the mean (SD) age was 25.1 (4) years, mean weight was 69.0 kg, and the mean (SD) body mass index (BMI) was 23.7 (3) kg/m 2. In the comparator study, 58% (164/282) were women; the mean (SD) age was 27 (6.4) years, mean weight was 71 kg, and mean (SD) BMI was 24.2 (3) kg/m 2. In the dose-finding study, the AZD3582 750-, 1500-, and 2250-mg groups were superior to placebo in the primary variables “time to rescue medication (0–8 hours)” (hazard ratios [HRs] [95% CIs], 0.17 [0.07–0.42], P < 0.003; 0.23 [0.11–0.50], P < 0.001; and 0.15 [0.06–0.36], P < 0.001, respectively), “time to meaningful pain relief” (HRs [95% CIs], 3.42 [1.87–6.25], P < 0.003; 2.49 [1.37–4.50], P < 0.003; and 3.07 [1.70–5.55], P < 0.001, respectively), and MPID (analysis of covariance [ANCOVA] least squares mean [LSM] differences [95% CIs], 25.8 [17.3–34.4], P < 0.003; 20.4 [12.1–28.7], P < 0.003; and 29.3 [20.9–37.6], P < 0.001, respectively). AZD3582 and naproxen did not show any statistically significant differences for the 3 primary variables, except that naproxen was superior to the AZD3582 375-mg dose for the variables time to meaningful pain relief (HR difference, 0.48 [95% CI, 0.29–0.78], P < 0.004) and MPID (difference in ANCOVA LSM, -10.2, [95% CI, -18.2 to -2.2], P < 0.012). The median times to meaningful pain relief were 115 minutes for AZD3582 375 mg, 66 minutes for 750 mg, 85 min utes for 1500 mg, 81 minutes for 2250 mg, and 162 minutes for placebo ( P = NS, P = 0.003, P < 0.003, and P < 0.001, respectively). The median time tofirst res cue medication was 144 minutes for placebo, and <50% of the subjects on any of the AZD3582 doses or naproxen took rescue medication within 8 hours after dosing. In the comparator study, AZD3582 750 mg was superior to placebo in “time to rescue medicaton (0-24 hours)” (HR [95% CI], 0.4 [0.3-0.6], P < 0.001), “time to confirmed perceptible pain relief” (2.1 [1.1–3.8], P = 0.02), and MPID (11.9 [4.2–19.5], P = 0.002). However, inferiority of AZD3582 to rofecoxib for MPID could not be excluded (tolerance limit of 10 mm; P = NS for noninferiority testing). The median times to confirmed perceptible pain relief were 45 minutes for AZD3582 500 mg, 40 minutes for 750 mg, and 37 minutes for rofecoxib. The median times tofirst rescue medication were 218 minutes for AZD3582 500 mg, 365 minutes for 750 mg, 635 minutes for rofecoxib, and 90 minutes for placebo. Overall, AZD3582 was well tolerated. However, an effect on orthostatic blood pressure could not be excluded because there seemed to be more subjects with dizziness and orthostatic blood pressure reduction who were administered AZD3582 ≥750 mg. The proportions of patients with vertigo and decreased orthostatic blood pressure each group were as follows: AZD3582 500 mg, 6%; AZD3582 750 mg, 12%; rofecoxib, 3%; and placebo, 5%. Conclusions: AZD3582 750 mg had similar analgesic efficacy as equimolar doses of naproxen, but noninferiority to rofecoxib was not demonstrated.

Physical therapy and active exercises – An adequate treatment for prevention of late whiplash syndrome?: Randomized controlled trial in 200 patients

The aim of this study was to compare the effect of a physical therapy regimen including active exercises with the current standard treatment on reduction of pain 6 weeks and 6 months after whiplash injury caused by motor vehicle collision. Two hundred patients were enrolled in a prospective randomized controlled trial. In the standard group, treatment consisted of immobilization with a soft collar over 7 days. In the physical therapy group, patients were scheduled for 10 physical therapy appointments including active exercises within 14 days after enrollment. Pain intensity was rated by all patients daily during the first week, the sixth week, and 6 months after recruitment, using a numeric rating scale (0–10). Data analyses were performed by comparing the mean (over 1 week) pain scores between the two different treatment groups. Ninety-seven patients were randomly assigned to the standard treatment group and 103 to the physical therapy group. During the first week, there was no significant difference in mean pain intensity between the standard treatment group (4.76 ± 2.15) and the physical therapy group (4.36 ± 2.14). However, after 6 weeks, mean pain intensity was significantly ( p = 0.002) lower in the physical therapy group (1.49 ± 2.26 versus 2.7 ± 2.78). Similarly, after 6 months, significantly ( p < 0.001) less pain was reported in the physical therapy group (1.17 ± 2.13) than the standard treatment group (2.33 ± 2.56). We conclude that a physical therapy regimen which includes active exercises is superior in reducing pain 6 weeks and 6 months after whiplash injury compared to the current standard treatment with a soft collar.

The analgesic efficacy of intramuscular parecoxib sodium in postoperative dental pain

The parenteral cyclo-oxygenase, or COX, -2 selective inhibitor parecoxib sodium in a 40-milligram dose for intravenous/intramuscular, or i.v./i.m., administration is approved for postoperative pain in Europe, but not yet in the United States. However, previous trials in dental surgical patients have indicated that lower doses may be as effective. The authors enrolled 353 patients in a single-center, double-blind, placebo-controlled, dose-ranging study to compare the efficacy and tolerability of single i.m. doses of parecoxib (1-20 mg) with ketorolac tromethamine 30 mg i.m. after dental surgery. Pain assessments occurred at baseline and through 24 hours postdose. A 20-mg dose of parecoxib was significantly more effective than were 1-mg to 10-mg doses and than placebo. The analgesic onset of a 20-mg dose of parecoxib was similar to that of a 30-mg dose of ketorolac. The magnitude of analgesia with a 20-mg dose of parecoxib was significantly lower than that with ketorolac, according to the mean pain intensity difference, or PID, scores from one and one-half to four hours postdose or summed PID, or SPID, -categorical scores at six hours postdose. However, there was no significant difference in mean pain relief; total pain relief, or TOTPAR; and SPID-visual analog scale, or VAS, scores six hours postdose. Mean PID scores for parecoxib 20 mg from 12 to 24 hours postdose were significantly higher than and SPID-VAS mean scores were not statistically significantly different from eight hours onward. Parecoxib 20 mg i.m. is an effective analgesic dose with an onset and magnitude of analgesic effect approaching that of ketorolac 30 mg i.m. after dental surgery. It also is well-tolerated. These findings support the use of parecoxib 20 mg i.m. as an initial dosing option for postoperative pain management in countries in which it is approved.

Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: A single-center, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model

Background: The combination of tramadol and acetaminophen has demonstrated good efficacy in various clinical pain models. However, there is a need for comparisons of the onset of analgesia and other measures of analgesic efficacy with this combination and other strong combination analgesics for the management of acute pain.Objective: The goal of this study was to compare the time to onset of analgesia and other measures of analgesic efficacy with tramadol/acetaminophen 75/650 mg (Tr/Ac) and codeine/acetaminophen/ibuprofen 20/500/400 mg (Co/Ac/Ib) in the management of acute pain after oral surgery.Methods: This was a single-center, single-dose, randomized, active-controlled, parallel-group study in healthy subjects who had undergone surgical extraction of ≥1 impacted third molar requiring bone removal. When patients reported at least moderate pain after dental surgery (score ≥5 on a 10-point scale), they were randomized to 1 of 2 treatment groups. The time to onset of analgesia was measured using a 2-stopwatch technique. The time to the onset of perceptible and meaningful pain relief, pain intensity, pain relief, patient's overall assessment, and adverse events were recorded for 6 hours after dosing.Results: One hundred twenty-eight subjects participated in the study, 64 in each treatment group. The 2 groups were similar in terms of baseine pain severity and demographic characteristics (mean age, 23.7 and 23.4 years in the Tr/Ac and Co/Ac/Ib groups, respectively; mean body weight, 58.5 and 60.3 kg). The median times to the onset of perceptible pain relief were a respective 21.0 and 24.4 minutes, and the median times to the onset of meaningful pain relief were 56.4 and 57.3 minutes. Mean total pain relief and the sum of pain intensity difference were also similar in the early period after dosing (0–4 hours). However, between 4 and 6 hours, Co/Ac/Ib was associated with significant differences in both variables compared with Tr/Ac (P < 0.05). Although similar through the 4-hour assessment, mean pain intensity difference was significantly greater with Co/Ac/Ib at 5 to 6 hours. The proportion of patients assessing their assigned treatment as good or better was significantly greater with Co/Ac/Ib compared with Tr/Ac (P < 0.05). The safety profile of Tr/Ac was comparable to that of Co/Ac/Ib.Conclusions: In this small and selected group of subjects, the onset of analgesia and analgesic efficacy of Tr/Ac was comparable to that of Co/Ac/Ib. Tr/Ac provided rapid and effective analgesia for acute postoperative dental pain in this population.

Traitement des signes fonctionnels des rhinosinusites maxillaires aiguës de l’adulte: Efficacité et tolérance de la prednisone administrée par voie orale pendant 3 jours

Acute maxillary rhinosinusitis (AMRS) is a pathology in which the pain is often severe and requires appropriate treatment. Although the use of antibiotics is widely documented, the interest of short cycles of corticosteroids in the treatment of the functional manifestations of AMRS is based on professional experience. The aim of this study was to assess the efficacy and tolerance to prednisone administered for 3 days in addition to antibiotherapy in patients presenting with an AMRS. This was a double blind, randomised study in parallel groups and controlled versus a placebo, involving patients aged over 18, presenting with an AMRS confirmed by X-ray and endoscopy, having developed less than 5 days and complaining of spontaneous pain assessed as >or=50 millimetres on a visual analog scale (VAS). Together with cefpodoxime, the patients received either prednisone (0.8 to 1.2 mg/kg) for 3 days or a placebo. The primary efficacy endpoint was the mean of the differences versus the baseline value of pain (MPID - mean pain intensity difference) assessed on the VAS from Day 1 to Day 3. The secondary endpoints assessed were the mean of the differences in intensity of nasal obstruction, assessed in the same way as the MPID, the time lapse before the orally expressed relief of the pain (PRID - pain reflief intensity difference) and the administration of paracetamol during the first 3 days. 289 patients (placebo 147, prednisone 142) were assessable for analysis in intent-to-treat (ITT). The global spontaneous pain on inclusion, measured by a VAS was of 73.0 +/- 14.1 mm. The assessments made during the first 3 days of treatment showed a statistically significant difference in favour of the prednisone group regarding MPID: - 4.82 mm (CI 95% -9.25; -0.40) (p=0.03), nasal obstruction - 5.0 mm (CI 95% -9.1; -0.8) (p=0.02) and consumption of paracetamol (p=0.03). There was no difference between the two groups after the end of the antibiotherapy. The tolerance measured throughout the study was comparable between the two groups. This study clearly showed the efficacy of a short course of oral prednisone (3 days), versus a placebo, in the treatment of the functional signs of acute maxillary rhinosinusitis with severe pain in adults in addition to an appropriate antibiotic treatment.

Oral Tramadol for the Treatment of Pain of 7–30 Days’ Duration in Children

Oral Tramadol for the Treatment of Pain of 7–30 Days’ Duration in Children