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Attempting to Separate Placebo Effects from Exercise in Chronic Pain: A Systematic Review and Meta-analysis.
Miller, CT, Owen, PJ, Than, CA, Ball, J, Sadler, K, Piedimonte, A, Benedetti, F, Belavy, DL
Sports medicine (Auckland, N.Z.). 2022;(4):789-816
Abstract
BACKGROUND Pain is the most disabling characteristic of musculoskeletal disorders, and while exercise is promoted as an important treatment modality for chronic musculoskeletal conditions, the relative contribution of the specific effects of exercise training, placebo effects and non-specific effects such as natural history are not clear. The aim of this systematic review and meta-analysis was to determine the relative contribution of these factors to better understand the true effect of exercise training for reducing pain in chronic primary musculoskeletal pain conditions. DESIGN Systematic review with meta-analysis DATA SOURCES MEDLINE, CINAHL, SPORTDiscus, EMBASE and CENTRAL from inception to February 2021. Reference lists of prior systematic reviews. ELIGIBILITY CRITERIA Randomised controlled trials of interventions that used exercise training compared to placebo, true control or usual care in adults with chronic primary musculoskeletal pain. The review was registered prospectively with PROSPERO (CRD42019141096). RESULTS We identified 79 eligible trials for quantitative analysis. Pairwise meta-analysis showed very low-quality evidence (GRADE criteria) that exercise training was not more effective than placebo (g [95% CI]: 0.94 [- 0.17, 2.06], P = 0.098, I2 = 92.46%, studies: n = 4). Exercise training was more effective than true, no intervention controls (g [95% CI]: 0.99 [0.66, 1.32], P < 0.001, I2 = 92.43%, studies: n = 42), usual care controls (g [95% CI]: 0.64 [0.44, 0.83], P < 0.001, I2 = 76.52%, studies: n = 33), and when all controls combined (g [95% CI]: 0.84 [0.64, 1.04], P < 0.001, I2 = 90.02%, studies: n = 79). CONCLUSIONS There is very low-quality evidence that exercise training is not more effective than non-exercise placebo treatments in chronic pain. Exercise training and the associated clinical encounter are more effective than true control or standard medical care for reductions in pain for adults with chronic musculoskeletal pain, with very low quality of evidence based on GRADE criteria.
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Quality of life and functional outcomes with tapentadol prolonged release in chronic musculoskeletal pain: post hoc analysis.
Ferri, CM, Natoli, S, Sanz-Ayan, P, Magni, A, Guerrero, C, Lara-Solares, A, Liedgens, H, Thömmes, G, Karra, R
Pain management. 2021;(2):173-187
Abstract
Aims: To investigate quality of life (QOL) and functionality changes in chronic pain during tapentadol prolonged release (PR) treatment. Patients & methods: Post hoc analysis of data from three Phase III trials in patients with osteoarthritis knee pain or low back pain. QOL and functionality changes were assessed by SF-36 scores. Results: All SF-36 subdomain scores improved progressively to week 3 of tapentadol titration and were sustained during 12-week maintenance treatment. Improvements in SF-36 scores were similar between tapentadol dose groups (e.g., 200 to <300 mg vs ≥500 mg), with no greater effect from higher doses. QOL and functionality improvements were consistently greater with tapentadol PR than oxycodone controlled release. Conclusion: Tapentadol PR provides consistent, clinically relevant improvements in QOL and functionality in chronic pain.
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Comparing two doses of intramuscular ketorolac for treatment of acute musculoskeletal pain in a military emergency department.
Turner, NJ, Long, DA, Bongiorno, JR, Katoski, TP, Jin, LM, Horsch, JP, Ahern, BJ
The American journal of emergency medicine. 2021;:142-147
Abstract
STUDY OBJECTIVE The goal of the study was to assess a low-dose versus a high-dose of intramuscular (IM) ketorolac for non-inferiority in adults with acute MSK pain in an emergency department (ED). METHODS This was a single-blinded, randomized controlled, non-inferiority trial of adults presenting to an ED with a chief complaint of acute MSK pain. Patients were randomized to either a 15 mg or a 60 mg IM ketorolac dose. The primary outcome was the mean difference of change in pain from baseline to 60-min between the two groups as reported on a 100-mm (mm) visual analog scale (VAS). Secondary outcomes included the mean difference of change in VAS scores at 30-min and the incidence of reported adverse effects associated with the administration of ketorolac. RESULTS One hundred ten patients were randomized with 55 in each group. The mean difference in pain between groups at 60-min (0.2 mm [95% CI -8.5-8.7]; p = .98) and 30 min (-1.7 mm [95% CI -8.5-5.1; p = .63) was less than the predetermined non-inferiority margin of 13 mm. There were no major adverse effects reported. Minor adverse effects were more frequent in the 60 mg group (n = 9; 16.4% vs. n = 1; 1.8%; p = .016) with burning at the injection site being the most commonly reported. CONCLUSIONS A 15 mg dose of IM ketorolac was found to be non-inferior to a 60 mg dose for acute MSK pain in adults presenting to the ED. Discontinuing the practice of ordering 60 mg doses of IM ketorolac in place of a lower dose for acute MSK pain should be considered.
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Efficacy of high-dissolution turmeric-sesame formulation for pain relief in adult subjects with acute musculoskeletal pain compared to acetaminophen: A randomized controlled study.
Rudrappa, GH, Chakravarthi, PT, Benny, IR
Medicine. 2020;(28):e20373
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Abstract
BACKGROUND Acetaminophen (paracetamol) is one of the most commonly used over-the-counter for pain relief. Management of acute pain with plant-based nutrients has remained suboptimal due to an absence of data supporting acute relief of pain. In the present study, it was hypothesized that high-dissolution liquid treatment of black sesame extract oil, Curcuma longa and Boswellia serrata may provide pain relief in people with acute musculoskeletal pain as quickly as acetaminophen. METHODS In this randomized active controlled open label study, 88 healthy subjects with acute musculoskeletal pain were randomized to receive treatment capsule (Rhuleave-K; 1,000 mg/d) or 1,000 mg/d acetaminophen for 7 days. Change in pain intensity and pain relief at first 6 hours, 3 days, and 7 days were measured. The onset of analgesia was measured by perceptible pain relief and meaningful pain relief. Other measures were McGill Pain Questionnaire and Patient Global Impression Change. RESULTS The treatment formulation resulted in average magnitude of pain relief comparable to the acetaminophen. Sixty-six percent of subjects in the treatment group reported positive response in pain relief (≥50% max TOTPAR; total pain relief) after 6 hours, compared to 73% of control. Seventy-three percent of subjects on treatment were considered positive responders, compared to 80% in the control group. The average time of onset of analgesia was 1 hour for the treatment group, versus 0.83 hour for control. At the end of day 3 and 7, there was significant improvement (P < .001 for day 3 and day 7) in the pain condition of treatment group and was comparable to control (P = .436 for day 3 and P = .529 for day 7). The total McGill Pain score showed significant reduction in pain with the treatment irrespective of the pain intensity statistically equal (P = .468) to control. Both the groups were equal in providing sensory pain relief (P = .942), but the treatment was 8.57 times significantly better (P = .027) than acetaminophen in reducing the unpleasantness and emotional aspects (affective domain) involved with acute pain. CONCLUSION The results showed that the treatment used in the study may act as a natural, fast acting, and safe alternative for acute pain relief comparable to acetaminophen.
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Nutritional factors in chronic musculoskeletal pain: unravelling the underlying mechanisms.
Elma, Ö, Yilmaz, ST, Deliens, T, Coppieters, I, Clarys, P, Nijs, J, Malfliet, A
British journal of anaesthesia. 2020;(2):e231-e233
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Intravenous paracetamol versus dexketoprofen in acute musculoskeletal trauma in the emergency department: A randomised clinical trial.
Yilmaz, A, Sabirli, R, Ozen, M, Turkcuer, I, Erdur, B, Arikan, C, Demirozogul, E, Sarohan, A, Seyit, M, Ok, N
The American journal of emergency medicine. 2019;(5):902-908
Abstract
INTRODUCTION Musculoskeletal system traumas are among the most common presentations in the emergency departments. In the treatment of traumatic musculoskeletal pain, paracetamol and non-steroidal anti-inflammatory analgesics (NSAID) are frequently used. Our aim in this study is to compare the efficacy of intravenous dexketoprofen and paracetamol in the treatment of traumatic musculoskeletal pain. METHODS This prospective, randomised, double blind, controlled study was conducted in a tertiary care emergency unit. The participating patients were randomised into two groups to receive either 50 mg of dexketoprofen or 1000 mg of paracetamol intravenously by rapid infusion in 150 mL of normal saline. Visual analogue scale (VAS), Numeric Rating Scala (NRS) and Verbal Rating Scale (VRS) was employed for pain measurement at baseline, after 15, after 30 and after 60 mins. RESULTS 200 patients were included in the final analysis. The median age of the paracetamol group was 34 (24-48), while that of the dexketoprofen group was 35 (23-50), and 63% (n = 126) of them consisted of men. Paracetamol and dexketoprofen administration reduced VAS pain scores over time (p = 0.0001). Median reduction in VAS score at 60 min was 55 (IQR 30-65) for the paracetamol group and 50(IQR 30.25-60) for the dexketoprofen group. There was no statistically significant difference between the paracetamol and dexketoprofen groups in terms of VAS reductions (p = 0.613). CONCLUSION Intravenous paracetamol and dexketoprofen seem to produce equivalent pain relief for acute musculoskeletal trauma in the emergency department. CLINICALTRIALS. GOV NO NCT03428503.
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Intravenous dexketoprofen versus paracetamol in non-traumatic musculoskeletal pain in the emergency department: A randomized clinical trial.
Demirozogul, E, Yilmaz, A, Ozen, M, Turkcuer, I, Seyit, M, Arikan, C
The American journal of emergency medicine. 2019;(12):2136-2142
Abstract
INTRODUCTION Although acute musculoskeletal pain has a wide range of causes from tendinitis, muscle spasm, to bone and joint injuries, it is a frequent occurrence in emergency services. Paracetamol and non-steroidal anti-inflammatory analgesics (NSAID) are common used in the treatment of musculoskeletal pain. This study sets out to compare the effectiveness of intravenous dexketoprofen and paracetamol in musculoskeletal pain relief. METHODS This prospective, randomized, double blind, controlled study was carried out in a university emergency room. The participating patients were randomized into two groups to receive either 50 mg of dexketoprofen or 1000 mg of paracetamol intravenously by rapid infusion in 150 ml of normal saline. Visual analogue scale (VAS), Numeric Rating Scala (NRS) was employed for pain measurement at baseline, after 15, after 30 and after 60 mins. RESULTS 200 patients were included in the study, excluding 7342 of them. The mean age of the patients was calculated as 32,6. Paracetamol and dexketoprofen intervention decreases NRS pain scores over time. When compared to all pain locations, the NRS pain score of the patients was found to be statistically more effective in dexketoprofen than in paracetamol (p = 0.001). Paracetamol and dexketoprofen intervention reduces pain VAS scores over time. When the VAS pain score of the patients was compared to all pain locations, dexketoprofen was found to be statistically more effective than paracetamol (p = 0.001). CONCLUSION Intravenous dexketoprofen seemed to achieve superior analgesia to intravenous paracetamol when compared with all pain locations in patients with non-traumatic musculoskeletal pain.
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Trends in Prescription Analgesic Use Among Adults With Musculoskeletal Conditions in the United States, 1999-2016.
Stokes, A, Berry, KM, Hempstead, K, Lundberg, DJ, Neogi, T
JAMA network open. 2019;(12):e1917228
Abstract
IMPORTANCE Monitoring trends in prescription analgesic use among adults with musculoskeletal conditions provides insight into how changing prescribing practices, guidelines, and policy measures may affect those who need pain management. OBJECTIVE To evaluate trends in prescription opioid use and nonopioid analgesic use among adults with functional limitations attributable to musculoskeletal conditions. DESIGN, SETTING, AND PARTICIPANTS This repeated cross-sectional study uses data from the National Health and Nutrition Examination Study from 1999 to 2016. Data were analyzed from January to July 2019. The participants were adults aged 30 to 79 years who reported functional limitations due to back or neck problems and/or arthritis or rheumatism. MAIN OUTCOMES AND MEASURES Any use of a prescription opioid or exclusive use of a prescription nonopioid analgesic. RESULTS In this population of 7256 adults with 1 or more functional limitations attributable to a musculoskeletal condition (4226 women [59.9%]; 3508 [74.4%] non-Hispanic white individuals; median [interquartile range] age, 63 [53-70] years), opioid use and exclusive nonopioid analgesic use exhibited approximately reciprocal patterns of change from 1999 to 2016. Opioid use increased significantly (difference in prevalence for 2015-2016 vs 1999-2000, 7.2%; 95% CI, 1.3% to 13%; P for trend = .002), and exclusive use of nonopioid analgesics decreased significantly (difference in prevalence for 2015-2016 vs 1999-2000, -13%; 95% CI, -19% to -7.5%; P for trend < .001) during this period. The increase in any opioid use was driven by long-term rather than short-term use. A crossover in the prevalence of opioid use and exclusive use of nonopioid analgesics occurred between 2003 and 2006, after which opioid use was more prevalent. Between 2013 and 2016, decreases in opioid use were observed among men (difference in prevalence for 2015-2016 vs 2013-2014, -11%; 95% CI, -21% to 1.8%) and participants with less than a high school education (difference, -15%; 95% CI, -24% to -6.1%). During this same period, exclusive nonopioid analgesic use also decreased markedly across the population (difference, -5.3%; 95% CI, -9.1% to -1.5%). CONCLUSIONS AND RELEVANCE The substitution of opioids for nonopioid analgesics between 2003 and 2006 may have occurred as evidence emerged on the cardiovascular risks associated with nonopioid analgesics. Reductions in opioid use between 2013 and 2016 were most substantial among those with low socioeconomic status, who may encounter barriers in accessing alternatives. Despite those decreases, opioid use remained more prevalent in 2015 to 2016 than in 1999 to 2000, suggesting a potentially long tail for the opioid epidemic.
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Dietary Ingredients Requiring Further Research Before Evidence-Based Recommendations Can Be Made for Their Use as an Approach to Mitigating Pain.
Crawford, C, Boyd, C, Berry, K, Deuster, P, ,
Pain medicine (Malden, Mass.). 2019;(8):1619-1632
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Abstract
OBJECTIVE Approximately 55-76% of Service members use dietary supplements for various reasons; although such use has become popular, decisions are often driven by information that is not evidence-based. This work evaluates whether current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. Grading of Recommendations, Assessment, Development and Evaluation was used to determine confidence in the effect estimates. The committee used a decision table to make evidence-informed judgments across decision-making factors and recommendations for practice and self-care use. RESULTS Nineteen dietary ingredients were assessed. No recommendations were given for boswellia, ginger, rose hip, or s-adenosyl-L-methionine (SAMe); specifically, although ginger can be obtained via food, no recommendation is provided for use as a supplement due to unclear research. Further, there were insufficient strong research on boswellia and SAMe and possible compliance issues (i.e., high number of capsules required daily) associated with rose hip. CONCLUSIONS No recommendations were made when the evidence was low quality or trade-offs were so closely balanced that any recommendation would be too speculative. Research recommendations are provided to enhance the quality and body of evidence for the most promising ingredients. Clinicians and those with chronic pain can rely on evidence-based recommendations to inform their decisions.
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Vitamin D supplementation and musculoskeletal health.
Bouillon, R, Lips, P, Bilezikian, JP
The lancet. Diabetes & endocrinology. 2019;(2):85-86