Mean Pain Reduction Research Articles

Efficacy of pelvic floor muscle training with physical therapy for low back pain: A systematic review and meta-analysis.

To assess the efficacy of pelvic floor muscle training and physical therapy interventions in patients with low back pain. The Ovid-Medline, Ovid-Embase, Cochrane Library, CINAHL, Web of Science, and PEDro databases were searched for randomised, controlled trials published in English or Korean between database inception and September 2024. Studies providing pelvic floor muscle training in individuals with low back pain were included. The risk of bias using the Cochrane Risk of Bias 2 tool and the grading of recommendation, assessment, development, and evaluation (GRADE) system was used to evaluate the quality of evidence. The meta-analysis was performed using Review Manager software 5.4. Nineteen studies were included in this review. Pelvic floor muscle training showed low certainty evidence for improving pain (standardised mean difference = -0.73, 95% CI [-1.10, -0.36]) and reflected a clinically meaningful reduction in pain. The evidence for disability improvement had a low certainty (mean difference = -5.21, 95% CI [-7.15, -3.26]) due to high heterogeneity. Substantial improvements in pain and disability were observed when pelvic floor muscle training was added to standard physical therapy, with low certainty of evidence supporting these findings. Whereas pelvic floor muscle training substantially improved pain compared to other interventions, there was no marked improvement in disability. Pelvic floor muscle training is potentially beneficial in addition to physical therapy for reducing low back pain, particularly in pregnancy-related cases. However, the evidence should be interpreted considering the quality and risk of bias.

Genicular artery embolisation versus sham embolisation for symptomatic osteoarthritis of the knee: a randomised controlled trial

ObjectiveTo determine the efficacy of genicular artery embolisation (GAE) compared with sham GAE for pain reduction in patients with symptomatic mild-to-moderate knee osteoarthritis (KOA).DesignDouble-blind randomised sham-controlled clinical trial conducted from...

Extended reality used in the treatment of phantom limb pain: a multicenter, double-blind, randomized controlled trial

Abstract Phantom limb pain (PLP) represents a significant challenge after amputation. This study investigated the use of phantom motor execution (PME) and phantom motor imagery (PMI) facilitated by extended reality (XR) for the treatment of PLP. Both treatments used XR, but PME involved overt execution of phantom movements, relying on the decoding of motor intent using machine learning to enable real-time control in XR. In contrast, PMI involved mental rehearsal of phantom movements guided by XR. The study hypothesized that PME would be superior to PMI. A multicenter, double-blind, randomized controlled trial was conducted in 9 outpatient clinics across 7 countries. Eighty-one participants with PLP were randomly assigned to PME or PMI training. The primary outcome was the change in PLP, measured by the Pain Rating Index, from baseline to treatment cessation. Secondary outcomes included various aspects related to PLP, such as the rate of clinically meaningful reduction in pain (CMRP; >50% pain decrease). No evidence was found for superiority of overt execution (PME) over imagery (PMI) using XR. PLP decreased by 64.5% and 68.2% in PME and PMI groups, respectively. Thirty-seven PME participants (71%) and 19 PMI participants (68%) experienced CMRP. Positive changes were recorded in all other outcomes, without group differences. Pain reduction for PME was larger than previously reported. Despite our initial hypothesis not being confirmed, PME and PMI, aided by XR, are likely to offer meaningful PLP relief to most patients. These findings merit consideration of these therapies as viable treatment options and alternatives to pharmacological treatments.

Real-World Implementation of Simulation-Free Radiation Therapy (SFRT-1000): A Propensity Score-Matched Analysis of 1000 Consecutive Palliative Courses Delivered in Routine Care.

The feasibility of simulation-free radiation therapy (SFRT) has been demonstrated but information regarding its routine care impact and scalability is lacking. In this single-institution, retrospective cohort study, all patients receiving palliative radiation therapy at an Australian tertiary cancer center were eligible for consideration of SFRT unless mask immobilization, a stereotactic technique, or a definitive dose was indicated. Coprimary endpoints were SFRT utilization, impact on consultation-to-RT time, and on-couch treatment duration. Timing metrics were compared with a contemporary local cohort that received simulation-based palliative radiation therapy using unadjusted Wilcoxon rank-sum tests and a propensity score-matched regression. Electronic patient-reported outcomes captured 2-week toxicity and pain response. Between April 2018 and February 2024, 2849 palliative radiation courses were delivered, of which 1904 were eligible. Of the 1904 courses, 1000 (52.5% SFRT utilization) received SFRT, including 668 using intensity-modulated radiation therapy/volumetric-modulated arc therapy. A total of 788 individual patients received SFRT and the median age was 71 years (IQR, 61-80) with 59% being male and 42% being Eastern Collaborative Oncology Group 2-4. SFRT utilization increased from 41% to 54% between years 2018-2019 and 2022-2024. SFRT reduced median consultation-to-RT time from 7.0 to 5.1 days (P < .0001) corresponding to an adjusted average treatment effect in the treated of -2.1 days (95% CI, -2.8 to -1.3). SFRT increased median on-couch treatment duration from 17.8 to 20.5 minutes (P < .0001; adjusted average treatment effect in the treated 2.6 minutes, 95% CI, 1.3-3.9). Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events grade 3 acute toxicity was 9% and at 4 weeks after RT, patients with moderate/severe pain at baseline (≥5/10) had a mean pain reduction of 3.5 points (7.1-3.6; P < .0001). Using widely available technologies, the SFRT-1000 cohort demonstrates routine care scalability with patient-centered and workflow benefits. SFRT is an attractive new paradigm implementable in most settings following adaptation to local requirements. Thus, SFRT opens new avenues to potentially improve access to palliative RT, which remains a global area of need.

Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC).

108 Background: EV+P nearly doubled median progression-free survival and overall survival vs PBC in patients (pts) with previously untreated la/mUC in the phase 3 EV-302 trial. PROs are reported here. Methods: In EV-302 (NCT04223856) pts were randomized 1:1 to EV+P or PBC (gemcitabine with cisplatin or carboplatin). PRO assessments included the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), and the Brief Pain Inventory Short Form (BPI-SF) completed at baseline, weekly for 12 weeks (wks), then every 3 wks through survival follow-up, inclusive of the time post-progression. Time to pain progression (TTPP) and mean change from baseline in worst pain at wk 26 using the BPI-SF were prespecified analyses statistically tested using a gatekeeping strategy. Mean change from baseline through wk 26 and time to confirmed deterioration (TTCD) of EORTC-QLQ-C30 and BPI-SF domains were prespecified descriptive analyses. TTPP and TTCD were assessed using Kaplan-Meier methods. Results: Of 886 pts randomized, 731 (376 received EV+P; 355 PBC) completed baseline PRO questionnaires. Compliance rates differed between arms and remained &gt;70% through wk 29 for EV+P and through only wk 17 for PBC. Median TTPP was 14.2 months (mos) with EV+P and 10.0 mos with PBC (hazard ratio [HR]=0.92; 95% CI=0.72, 1.17; 2-sided p-value=0.48). The least squares (LS) mean reduction in worst pain at wk 26 was numerically greater with EV+P vs PBC (-0.61 vs -0.03, LS mean difference [95% CI]: -0.58 [-1.05, -0.11] [nominal 2-sided P = 0.015]). Pts with moderate to severe pain at baseline who were treated with EV+P (n=128, 34%) had a meaningful (&gt;2 pt) improvement from baseline in BPI worst pain from wk 3 through 26. In EORTC QLQ-C30 Global Health Status/Quality of Life [GHS/QoL], EV+P demonstrated a transient worsening at week 3 (-6.3) that returned to baseline from weeks 4 through 26, while patients treated with PBC demonstrated deterioration from week 1 through week 17 (range -1.2 to -7.1) where scores returned to baseline. TTCD for EORTC QLQ-C30 GHS/QoL was 5.9 mos with EV+P vs 3.2 mos with PBC (HR = 0.98 [95% CI]: 0.79 – 1.2). Conclusions: Pts treated with EV+P have improved survival compared with PBC without detriment to quality of life and functioning, further supporting the value of EV+P for pts with la/mUC. Compliance, especially after progression, was lower than expected (particularly in the PBC arm) and may have impacted the results. Clinical trial information: NCT04223856 .

Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL).

Resveratrol is a natural compound found in red wine. It has demonstrated anti-inflammatory properties in preclinical models. We compared the effect of oral resveratrol in a new patented formulation to oral placebo for individuals with painful knee osteoarthritis. ARTHROL was a double-blind, randomized, placebo-controlled, Phase 3 trial conducted in 3 tertiary care centers in France. We recruited adults who fulfilled the 1986 American College of Rheumatology criteria for knee osteoarthritis and reported a pain intensity score of at least 40 on an 11-point numeric rating scale (NRS) in 10-point increments (0, no pain, to 100, maximal pain). Participants were randomly assigned (1:1) by using a computer-generated randomization list with permuted blocks of variable size (2, 4, or 6) to receive oral resveratrol (40 mg [2 caplets] twice a day for 1 week, then 20 mg [1 caplet] twice a day; resveratrol group) or matched oral placebo (placebo group) for 6 months. The primary outcome was the mean change from baseline in knee pain on a self-administered 11-point pain NRS at 3 months. The trial was registered at ClinicalTrials.gov: (NCT02905799). Between October 20, 2017 and November 8, 2021, we assessed 649 individuals for eligibility, and from November 9, 2017, we recruited 142 (22%) participants (mean age 61.4 years [standard deviation (SD) 9.6] and 101 [71%] women); 71 (50%) were randomly assigned to the resveratrol group and 71 (50%) to the placebo group. At baseline, the mean knee pain score was 56.2/100 (SD 13.5). At 3 months, the mean reduction in knee pain was -15.7 (95% confidence interval (CI), -21.1 to -10.3) in the resveratrol group and -15.2 (95% CI, -20.5 to -9.8) in the placebo group (absolute difference -0.6 [95% CI, -8.0 to 6.9]; p = 0.88). Serious adverse events (not related to the interventions) occurred in 3 (4%) in the resveratrol group and 2 (3%) in the placebo group. Our study has limitations in that it was underpowered and the effect size, estimated to be 0.55, was optimistically estimated. In this study, we observed that compared with placebo, oral resveratrol did not reduce knee pain in people with painful knee osteoarthritis. ClinicalTrials.gov ID: NCT02905799.

Varus Thrust Assessment Identified Responders to Quadriceps Exercise in Individuals at Risk of or with Knee Osteoarthritis.

Identification of responders/non-responders to unsupervised therapeutic exercise represents a critical challenge towards establishment of tailored self-management at home. Focusing on visualized varus thrust during gait as a possible effect moderator, this study determined whether and how varus thrust influences the therapeutic effects of home-based quadriceps exercise in individuals at increased risk of, or with, established knee osteoarthritis. This study is a secondary subgroup analysis of a randomized controlled trial (n = 50). Varus thrust at baseline was assessed via recorded gait movie. Analysis of covariance and subsequent mediation analysis were used to determine whether and how varus thrust influences the therapeutic effect of home-based quadriceps exercise after adjustment for covariates. To address the possible distinct impact of varus thrust on unsupervised and supervised exercise, the results were cross-checked with previous supervised exercise cohort using a meta-analysis. Individuals without varus thrust displayed greater and clinically meaningful pain-relief after exercise after adjustment for covariates. The greater pain-relief in individuals without varus thrust was attributed, at least partly, to an improvement in knee flexion range of motion. Notably, the meta-analysis revealed that unsupervised and supervised exercise programs induce consistent and clinically meaningful pain reduction in individuals without varus thrust. Varus thrust is a robust effect moderator of the pain reducing effect of quadriceps exercise. Further, greater pain reduction may be a function of improvement of knee flexion range of motion. These studies provide evidence that varus thrust assessment represents valuable approach to identify responders/non-responders to quadriceps exercise even for unsupervised protocol at their home environment.

Effectiveness of McKenzie exercises plus stabilization exercises versus McKenzie exercises alone on disability, pain, and range of motion in patients with nonspecific chronic neck pain: A randomized clinical trial.

Chronic nonspecific neck pain is a common disorder that causes disability and reduced quality of life. Effective conservative treatment options are needed to manage this condition. This randomized trial compared the efficacy of McKenzie exercises alone versus McKenzie plus cervical and scapulothoracic stabilization training for patients with chronic nonspecific neck pain. A randomized controlled trial was conducted in an outpatient physical therapy clinic. 76 patients with chronic (> 3 months) neck pain were randomized to 6 weeks of either McKenzie exercises alone (n= 38) or McKenzie plus stabilization exercise (n= 38). The McKenzie protocol included posture correction, range of motion exercises, and lateral neck stretches. The stabilization program added targeted exercises for the neck and scapula. The combination of McKenzie plus stabilization exercises resulted in significantly greater reduction in current neck pain intensity compared to McKenzie alone at 6 weeks (mean difference: -1.2 points on 0-10 scale, 95% CI -1.8 to -0.6; p< 0.001). Neck disability improved in both groups. Cervical range of motion also improved more with the addition of stabilization, except for extension. Adding specific cervical and scapulothoracic stabilization exercises to a standard McKenzie protocol led to clinically meaningful reductions in neck pain compared to McKenzie therapy alone in patients with chronic nonspecific neck pain. This combined approach can improve outcomes.

O-269 Long term efficacy of Linzagolix in women with endometriosis-associated pain

Abstract Study question Does once-daily linzagolix taken up to 12 months maintain pain reduction observed at 6 months in women with endometriosis? Summary answer Linzagolix alone or in combination with combined add-back therapy (ABT) for 12 months maintains improvements of endometriosis-associated pain (EAP) observed at 6 months. What is known already Linzagolix is an oral GnRH antagonist under development for EAP. In the EDELWEISS 3 study, the 200mg+ABT dose met its co-primary endpoints at 3 months by reducing dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP) and secondary endpoints such as DYS, NMPP, overall pelvic pain and dyschezia as well as interference of pain with daily activities at 6 months. Linzagolix 75mg significantly reduced dysmenorrhea but not NMPP at 3 months. Both doses of linzagolix were well tolerated over 6 months of treatment. Study design, size, duration EDELWEISS 6 was the extension study of EDELWEISS 3, a placebo-controlled Phase 3 study, investigating linzagolix 75mg and 200mg+ABT for up to 6 months in women with moderate to severe EAP. Subjects who completed EDELWEISS3 were invited to enter the extension study for an additional 6-month treatment on the same linzagolix dose; placebo subjects were randomized to either active dose. After end of treatment, subjects entered a drug-free post-treatment period of 6 months. Participants/materials, setting, methods Women participating to EDELWEISS 6 received linzagolix for up to 12 months consecutively. Key efficacy assessments included dysmenorrhea and non-menstrual pelvic pain (NMPP), dyspareunia (assessed with a 4-point VRS), overall pelvic pain and dyschezia (assessed with an 11-point NRS), and interference of pain with daily activities (assessed with the EHP-30 pain domain) at Month 12. We report the results for dysmenorrhea and NMPP. Main results and the role of chance Of 484 participants in EDELWEISS 3, 353 (72.9%) entered EDELWEISS 6 and were evaluated for efficacy. Demographics were similar to EDELWEISS 3 with a mean age of 35 years, a BMI of 24kg/m2 and 99% of subjects being White. Mean (SD) monthly baseline dysmenorrhea and NMPP pain scores on the VRS were 2.28 (0.41) and 1.76 (0.45), respectively. The threshold for a meaningful pain reduction was established at Month 3, being -1.10 and -0.80 for dysmenorrhea and NMPP, respectively. At Month 3, the proportion of subjects with a reduction of dysmenorrhea of 1.10 or greater, and stable or decreased use of analgesics was 45.2% for the 75mg group and 75.4% for the 200mg+ABT group, which increased to 49.6% and 84.7%, respectively, at Month 6, the end of EDELWEISS 3. At Month 12, the end of EDELWEISS 6 treatment, the proportion of subjects was further increased to 55.9% and 91.0%, respectively. For NMPP, the proportion of subjects with a reduction of 0.80 or greater and stable or decreased use of analgesics at Month 3 was 36.5% for 75 mg and 51.7% for 200mg+ABT, increased to 54% and 61% at Month 6, and increased to 59.5% and 67.6%, respectively, until Month 12. Limitations, reasons for caution Edelweiss 6 is the extension of the previously reported double blind, placebo controlled Edelweiss 3 study. The results confirm efficacy of 200mg + ABT at 12 months. Longer term data is required to further understand efficacy of GnRH antagonists in women with endometriosis associated pain. Wider implications of the findings The linzagolix 200mg+ABT group provided substantial and sustained improvement in EAP symptoms. The 75mg which did not meet the primary endpoint in EDELWEISS 3 still demonstrated marked improvements. There exists a substantial need for different treatment regimens in women suffering from endometriosis. Trial registration number NCT04335591

Rates and Predictors of Pain Reduction With Intracranial Stimulation for Intractable Pain Disorders.

Intracranial modulation paradigms, namely deep brain stimulation (DBS) and motor cortex stimulation (MCS), have been used to treat intractable pain disorders. However, treatment efficacy remains heterogeneous, and factors associated with pain reduction are not completely understood. We performed an individual patient review of pain outcomes (visual analog scale, quality-of-life measures, complications, pulse generator implant rate, cessation of stimulation) after implantation of DBS or MCS devices. We evaluated 663 patients from 36 study groups and stratified outcomes by pain etiology and implantation targets. Included studies comprised primarily retrospective cohort studies. MCS patients had a similar externalized trial success rate compared with DBS patients (86% vs 81%; P = .16), whereas patients with peripheral pain had a higher trial success rate compared with patients with central pain (88% vs 79%; P = .004). Complication rates were similar for MCS and DBS patients (12% vs 15%; P = .79). Patients with peripheral pain had lower likelihood of device cessation compared with those with central pain (5.7% vs 10%; P = .03). Of all implanted patients, mean pain reduction at last follow-up was 45.8% (95% CI: 40.3-51.2) with a 31.2% (95% CI: 12.4-50.1) improvement in quality of life. No difference was seen between MCS patients (43.8%; 95% CI: 36.7-58.2) and DBS patients (48.6%; 95% CI: 39.2-58) or central (41.5%; 95% CI: 34.8-48.2) and peripheral (46.7%; 95% CI: 38.9-54.5) etiologies. Multivariate analysis identified the anterior cingulate cortex target to be associated with worse pain reduction, while postherpetic neuralgia was a positive prognostic factor. Both DBS and MCS have similar efficacy and complication rates in the treatment of intractable pain. Patients with central pain disorders tended to have lower trial success and higher rates of device cessation. Additional prognostic factors include anterior cingulate cortex targeting and postherpetic neuralgia diagnosis. These findings underscore intracranial neurostimulation as an important modality for treatment of intractable pain disorders.

Alfentanil for Pain Relief in a Swedish Emergency Medical Service – An Eleven-Year Follow-up on Safety and Effect

Objectives Pain is a common symptom in prehospital emergency care and pain treatment in this context can be challenging. While previous research has assessed the use of morphine and other synthetic opioids for pain management in this setting, the evaluation of alfentanil is limited. The objective of this study was to evaluate the safety and effect of intravenous alfentanil when administered by ambulance nurses in prehospital emergency care. Methods This retrospective observational study consecutively included patients suffering from pain, treated with alfentanil in a Swedish EMS service from September 2011 to 31 September 2022. Data regarding occurrence of adverse events (AE), serious adverse events (SAE) – were used for safety evaluation and pain scores with a visual analogue scale (VAS) before and after treatment were used for evaluation of pain treatment. These data were extracted from the electronic patients’ medical records database for analysis. Univariate logistic regression analysis was used to identify significant predictors of AE following injection of alfentanil by nurses in prehospital emergency care. Results During the evaluation period 17,796 patients received pain relief with alfentanil. Adverse events affected 2.5% of the patients, while serious adverse events were identified in 25 cases (0.01%). Out of the 5970 patients with a complete VAS score for pain, the median VAS score was 8 (IQR 3) before treatment and 4 (IQR 3) after treatment. The mean reduction in pain measured by VAS was −4.1 ± 2.6 from the time before, to the evaluation after alfentanil administration. The administration frequency increased during the first year up to a steady level during the later part of the evaluation period. Conclusions This study proposes that alfentanil represents a safe and efficacious alternative for addressing urgent pain relief within the prehospital emergency context. Alfentanil demonstrates efficacy in alleviating pain across various conditions, with a relatively low risk of adverse events or serious adverse events when administered cautiously.

Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC).

4502 Background: EV+P nearly doubled median progression-free survival and overall survival vs PBC in patients (pts) with previously untreated la/mUC in the phase 3 EV-302 trial. PROs are reported here. Methods: In EV-302 (NCT04223856) pts were randomized 1:1 to EV+P or PBC (gemcitabine with cisplatin or carboplatin). PRO assessments included the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), and the Brief Pain Inventory Short Form (BPI-SF) completed at baseline, weekly for 12 weeks (wks), then every 3 wks through survival follow-up, inclusive of the time post-progression. Time to pain progression (TTPP) and mean change from baseline in worst pain at wk 26 using the BPI-SF were prespecified analyses statistically tested using a gatekeeping strategy. Mean change from baseline through wk 26 and time to confirmed deterioration (TTCD) of EORTC-QLQ-C30 and BPI-SF domains were prespecified descriptive analyses. TTPP and TTCD were assessed using Kaplan-Meier methods. Results: Of 886 pts randomized, 731 (376 received EV+P; 355 PBC) completed baseline PRO questionnaires. Compliance rates differed between arms and remained &gt;70% through wk 29 for EV+P and through only wk 17 for PBC. Median TTPP was 14.2 months (mos) with EV+P and 10.0 mos with PBC (hazard ratio [HR]=0.92; 95% CI=0.72, 1.17; 2-sided p-value=0.48). The least squares (LS) mean reduction in worst pain at wk 26 was numerically greater with EV+P vs PBC (-0.61 vs -0.03, LS mean difference [95% CI]: -0.58 [-1.05, -0.11] [nominal 2-sided p-value=0.015]). Pts with moderate to severe pain at baseline who were treated with EV+P (n=128, 34%) had a meaningful (&gt;2 pt) improvement from baseline in BPI worst pain from wk 3 through 26. In EORTC QLQ-C30 Global Health Status/Quality of Life [GHS/QoL], EV+P demonstrated a transient worsening at wk 3 (-6.3) that returned to baseline from wks 4 through 26, while patients treated with PBC demonstrated deterioration from wk 1 through wk 17 (range -1.2 to -7.1) when scores returned to baseline. TTCD for EORTC QLQ-C30 GHS/QoL was 5.9 mos with EV+P vs 3.2 mos with PBC (HR = 0.98 [95% CI]: 0.79 – 1.2). Conclusions: Pts treated with EV+P have improved survival compared with PBC without detriment to quality of life and functioning, further supporting the value of EV+P for pts with la/mUC. Compliance, especially after progression, was lower than expected (particularly in the PBC arm) and may have impacted the results. Clinical trial information: NCT04223856 .

Intravenous Acetaminophen Versus Ketorolac for Prehospital Analgesia: A Retrospective Data Review

BackgroundParenteral ketorolac and intravenous (IV) acetaminophen have been used for prehospital analgesia, yet limited data exist on their comparative effectiveness. Study ObjectivesTo evaluate the comparative effectiveness of IV acetaminophen and parenteral ketorolac for analgesia in the prehospital setting. MethodsWe conducted a retrospective cross-sectional evaluation of patients receiving IV acetaminophen or parenteral ketorolac for pain management in a large suburban EMS system between 1/1/2019 and 11/30/2021. The primary outcome was change in first to last pain score. Subgroup analysis was performed on patients with traumatic pain. We used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to estimate the treatment effect of acetaminophen versus ketorolac among all patients and the subgroup of those with traumatic pain. ResultsOf 2178 patients included, 856 (39.3%) received IV acetaminophen and 1322 (60.7%) received parenteral ketorolac. The unadjusted mean change in pain score was −1.9 (SD 2.4) for acetaminophen group and −2.4 (SD 2.4) for ketorolac. In the propensity score analyses, there was no statistically significant difference in pain score change for the acetaminophen group versus ketorolac among all patients (mean difference, IPTW: 0.11, 95% confidence interval [CI] −0.16, 0.37; PSM: 0.15, 95% CI −0.13, 0.43) and among those with traumatic pain (unadjusted: 0.18, 95% CI −0.35, 0.72; IPTW: 0.23, 95% CI −0.25, 0.71; PSM: −0.03, 95% CI −0.61, 0.54). ConclusionsWe found no statistically significant difference in mean pain reduction of IV acetaminophen and parenteral ketorolac for management of acute pain.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial

BackgroundAcute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. ObjectiveThe present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. Design, setting, participants and interventionsThe current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). Main outcome measuresThe primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient’s and investigator’s global evaluations of therapeutic response. ResultsThe mean reduction in pain was −51.22 mm (95% confidence interval [CI], [−53.42, −49.03] mm) for the HZG and −52.00 mm (95% CI, [−54.06, −49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [−2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). ConclusionHZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. Trial registrationChinese Clinical Trial Registry (ChiCTR2000036970).Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270–278.

Efficacy of Marham-e-Dakhilyun Ointment and Alum Perineal Wash for Perineal Wound Healing and Pain Intensity in Postpartum Women: A Self-control Clinical Trial

Background and Objective:: Episiotomy, worldwide, is the most frequently performed obstetric surgical procedure. Delayed wound healing potentially amplifies the risk of wound infection, structural muscular alterations, and ultimately contributes to the loss of muscle tone. In addition, rapid and complete repair of the episiotomy or perineal tear is very important as the pain and discomfort of episiotomy wounds may affect the quality of life of postnatal mothers. Therefore, we aimed to determine the efficacy of Marham-e-Dakhilyun ointment and alum perineal wash on perineal wound healing and pain intensity in postnatal mothers. Materials and Methods:: A single-arm self-controlled study was conducted on postnatal mothers aged 18 to 40 years, who underwent full-term normal cephalic singleton vaginal delivery with episiotomy and/or 1st, 2nd, or 3rd-degree perineal tears. The recommended external care regimen for a period of 10 days involved perineal wash with a solution of alum powder (2 gm/500ml), followed by the application of Marham-e Dakhilyun ointment twice daily to the perineal wound. For the primary evaluation of wound healing, the REEDA (redness, edema, ecchymosis, discharge, and approximation) scale has been utilized, while the secondary assessment involved the use of the VAS (visual analog scale) pain intensity scale. The therapeutic outcome was determined based on the grading of REEDA scores on days 10-14 and VAS scores. Results:: We observed our trial medicine showed complete wound healing in 86.4% on days 10- 14. The mean pain reduction percentage (PR %) was 96.85% on days 10-14 from baseline. The REEDA score was 2.41±0.81 and 0.23±0.61 at one hour and day 10-14, respectively, with significant differences (p &lt; 0.001). The VAS score was 2.86±1.08 and 0.09±0.29 at one hour and day 10-14, respectively, with significant differences (p &lt; 0.001). Therefore, the trial ointment and alum have demonstrated beneficial effects in promoting perineal wound healing and alleviating pain in postnatal mothers. Conclusion:: The potential efficacy of Marham-e-Dakhilyun can be attributed to its composition of various phytoconstituents, such as oleuropein, phenolic acids, flavonols, flavones, linoleic acid isovitexin, vitexin vanillic acid, salicylic acid, beta-D-glucopyranoside, olanigroside Y1, solasonine, gallic acid, aucubin, scopoletin, and lantamajoside. These constituents have been proven in research studies to possess anti-inflammatory, wound healing, antimicrobial, analgesic, and antioxidant properties. The investigators have optimized the use of these Unani medicines to provide clinical evidence supporting their effectiveness in the wound-healing process and in reducing pain intensity.

Microwave Energy for the Treatment of Painful Intractable Plantar Keratosis: A Retrospective Medical Record Review of Nine Patients.

Plantar keratoma are common hyperkeratinized, deep-seated lesions, often located on weightbearing areas of the foot. Such lesions are frequently associated with pain and disability. Intractable plantar keratomata (IPK) are highly recurrent and, in most patients, require regular, palliative treatment visits with a significant impact on patient time, cost, and quality of life. We undertook a retrospective chart review of 9 patients (with a total of 21 lesions) who underwent a minimum of two treatments using microwave therapy to their IPK. Pain levels were assessed at each of their treatments using a 10-point scale and patients were invited for review for follow-up in the following year. A total of seven patients undertook four treatments and were included in the final analysis. Mean baseline pain scores significantly dropped with each subsequent treatment, equating to a 90.4% mean reduction in pain between the first and fourth visits, with 71.4% of patients reporting a zero-pain rating at their final treatment visit. The use of microwave therapy has been shown to be effective in producing significant and prolonged pain reduction in a cohort of patients with painful IPK.

Treatment of Painful Diabetic Neuropathy with 10 kHz Spinal Cord Stimulation: Long-Term Improvements in Hemoglobin A1c, Weight, and Sleep Accompany Pain Relief for People with Type 2 Diabetes.

The recent SENZA-PDN study showed that high-frequency (10kHz) spinal cord stimulation (SCS) provided significant, durable pain relief for individuals with painful diabetic neuropathy (PDN), along with secondary benefits, including improved sleep quality and HRQoL. Given that metabolic factors and chronic neuropathic pain are related, we evaluated potential secondary effects of 10kHz SCS on hemoglobin A1c (HbA1c) and weight in SENZA-PDN participants with type 2 diabetes (T2D). This analysis included 144 participants with T2D and lower limb pain due to PDN who received 10kHz SCS during the SENZA-PDN study. Changes in HbA1c, weight, pain intensity, and sleep were evaluated over 24 months, with participants stratified according to preimplantation HbA1c (>7% and >8%) and body mass index (BMI; ≥30 and ≥35 kg/m2). At 24 months, participants with preimplantation HbA1c >7% and >8% achieved clinically meaningful and statistically significant mean reductions in HbA1c of 0.5% (P = 0.031) and 1.1% (P = 0.004), respectively. Additionally, we observed a significant mean weight loss of 3.1 kg (P = 0.003) across all study participants. In subgroups with BMI ≥30 and ≥35 kg/m2, weight reductions at 24 months were 4.1 kg (P = 0.001) and 5.4 kg (P = 0.005), respectively. These reductions were accompanied by a mean pain reduction of 79.8% and a mean decrease in pain interference with sleep of 65.2% at 24 months across all cohorts. This is the first study of SCS to demonstrate long-term, significant, and clinically meaningful reductions in HbA1c and weight in study participants with PDN and T2D, particularly among those with elevated preimplantation HbA1c and BMI. Although the mechanism for these improvements has yet to be established, the results suggest possible direct and indirect metabolic benefits with 10kHz SCS in addition to durable pain relief. ClincalTrials.gov Identifier, NCT03228420.

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.

Battlefield acupuncture for chronic musculoskeletal pain in cancer survivors: a novel care delivery model for oncology acupuncture.

Battlefield Acupuncture (BFA), a standardized auricular acupuncture protocol, is widely used for pain in the military but is not well-studied in oncology. This study examined cancer survivors who received BFA for pain. This is a secondary analysis of a randomized trial that compared the effectiveness of BFA and electroacupuncture vs. usual care for chronic musculoskeletal pain in cancer survivors. This study focused on participants randomized to BFA. Participants received 10 weekly treatments. Needles were placed until one of these stop conditions were satisfied: ten needles were administered; pain severity decreased to ≤1 out of 10; patient declined further needling, or vasovagal reaction was observed. Pain severity was assessed using Brief Pain Inventory. Responders were those with ≥30% pain severity reduction. We examined pain location, BFA stop reason, and pain reduction of participants during the first session. We also examined which factors predicted responder status after the first session (week 1) or the full treatment (week 12). Among 143 randomized to BFA, most common pain locations were lower back (30.8%) and knee/leg (18.2%). Of 138 who initiated treatment, 41 (30.0%) received ten needles; 81 (59.1%) achieved pain ≤1; 14 (10.2%) declined further needling; and 1 (0.7%) had vasovagal reaction. BFA reduced pain severity by 2.9 points (95% CI 2.6 to 3.2) after the first session (P < 0.001). After adjusting for baseline pain severity, responders at week 1 were 2.5 times more likely to be responders at week 12, compared to those who were non-responders at week 1 (AOR 2.5, 95% CI 1.02 to 6.11, P = 0.04). Among those who achieved pain ≤1, 74% were responders at week 12, a higher proportion compared to the proportion of responders among those who received ten needles (39.5%), those who declined further needling (50%), and those with vasovagal reaction (0.0%) (P = 0.001). Those with pain in proximal joints had a higher proportion of responders at week 12, compared to those with pain in distal joints (64.2% vs. 20%, P = 0.008). Specific factors may predict the likelihood of achieving meaningful pain reduction from BFA. Understanding these predictors could inform precision pain management and acupuncture delivery models.

Maintenance of Response to Risankizumab in Patients With Psoriatic Arthritis: A 3-year Analysis of the KEEPsAKE 1 and 2 Trials

Introduction: Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, specifically inhibits the p19 subunit of human interleukin 23 and is approved for treatment of active psoriatic arthritis (PsA) in adults. This post hoc analysis evaluated the long-term maintenance of clinical response through ~3 years of risankizumab treatment using data from 2 ongoing phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2.&#x0D; Methods: Eligible patients had active PsA with inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drugs (KEEPsAKE 1 [NCT03675308]; KEEPsAKE 2 [NCT03671148]) and/or inadequate response or intolerance to 1–2 biologic therapies (KEEPsAKE 2 only). Patients received double-blinded risankizumab 150 mg or placebo at weeks 0, 4, and 16 and open-label risankizumab 150 mg every 12 weeks thereafter. This analysis includes patients who received continuous risankizumab through both treatment periods. Assessments included improvement of ≥20%/50%/70% in PsA symptoms using American College of Rheumatology criteria (ACR20/50/70), achievement of minimal disease activity (MDA), reduction of ≥90% in Psoriasis Area and Severity Index (PASI 90; in patients with ≥3% body surface area affected by psoriasis at baseline), and clinically meaningful reduction in pain (≥10 mm on a visual analog scale [VAS]). Maintenance of response analyses were based on patients who were responders at weeks 24 or 52 for each endpoint. Nonresponder imputation incorporating multiple imputation (NRI-MI) for missing data due to COVID-19 or geopolitical conflict was used. As-observed data were also reported.&#x0D; Results: Among patients receiving continuous risankizumab, ACR20 was achieved at week 24 in 267/454 (KEEPsAKE 1, 58.8%) and 111/208 (KEEPsAKE 2, 53.4%) patients (as observed). Maintenance of response in week 24 ACR20 responders (NRI-MI) was achieved for ACR20 by most patients at week 52 (KEEPsAKE 1, 89.1%; KEEPsAKE 2, 77.0 %) and week 148 (KEEPsAKE 1, 74.7%; KEEPsAKE 2; 68.5%). Similar patterns of maintenance of response were observed for ACR50 and ACR70. Week 24 responders also maintained MDA at weeks 52 (KEEPsAKE 1, 82.2%; KEEPsAKE 2, 66.7%) and 148 (KEEPsAKE 1, 77.1%; KEEPsAKE 2, 71.9%). The PASI 90 response was maintained at weeks 52 (KEEPsAKE 1, 86.6%; KEEPsAKE 2, 88.4%) and 148 (KEEPsAKE 1, 76.3%; KEEPsAKE 2, 81.2%). Week 24 responders maintained clinically meaningful reductions in pain VAS at weeks 52 (KEEPsAKE 1, 83.9%; KEEPsAKE 2, 74.4%) and 148 (KEEPsAKE 1, 75.0%; KEEPsAKE 2, 72.0%). Comparable maintenance of response was recorded at week 148 for each endpoint among week 52 responders (NRI-MI).&#x0D; Conclusion: Risankizumab demonstrated durable long-term efficacy in patients with active PsA. A high proportion of patients receiving continuous risankizumab treatment in KEEPsAKE 1 and KEEPsAKE 2 achieved responses in ACR20/50/70, MDA, PASI 90, or pain VAS at weeks 24 or 52 and maintained responses through week 148.