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Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.
Gudbergsen, H, Overgaard, A, Henriksen, M, Wæhrens, EE, Bliddal, H, Christensen, R, Nielsen, SM, Boesen, M, Knop, FK, Astrup, A, et al
The American journal of clinical nutrition. 2021;(2):314-323
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Abstract
BACKGROUND Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.
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An Investigation into the Effects of a Curcumin Extract (Curcugen®) on Osteoarthritis Pain of the Knee: A Randomised, Double-Blind, Placebo-Controlled Study.
Lopresti, AL, Smith, SJ, Jackson-Michel, S, Fairchild, T
Nutrients. 2021;(1)
Abstract
Curcumin, a phytochemical from the spice turmeric, has anti-inflammatory properties and has been shown to have pain-relieving effects. In this 8-week, randomised, double-blind, placebo-controlled study, 101 adults with knee osteoarthritis received either 500 mg twice daily of a standardised curcumin extract (Curcugen®) or placebo. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee pain ratings, Japanese Orthopaedic Association Score for Osteoarthritic Knees (JOA), PROMIS-29, and performance-based testing comprising the 40-m fast-paced walk test, 6-min walk test, timed up-and-go test, and 30-s chair stand test. Compared to the placebo, curcumin significantly reduced the KOOS knee pain score (p = 0.009) and numeric knee pain ratings (p = 0.001). Curcumin was also associated with greater improvements (p ≤ 0.05) than the placebo on the timed up-and-go test, 6-min walk test, and the JOA total score; but not the 30-s chair stand test or 40-m fast-paced walk test. Pain-relieving medication was reduced in 37% of participants on curcumin compared to 13% on placebo. The findings support the potential efficacy of curcumin for the treatment of osteoarthritis of the knee but studies of longer duration, varying treatment doses, differing curcumin extracts, and the use of other objective outcome measures will be helpful to expand on these findings.
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Lamiaceae in Mexican Species, a Great but Scarcely Explored Source of Secondary Metabolites with Potential Pharmacological Effects in Pain Relief.
Hernandez-Leon, A, Moreno-Pérez, GF, Martínez-Gordillo, M, Aguirre-Hernández, E, Valle-Dorado, MG, Díaz-Reval, MI, González-Trujano, ME, Pellicer, F
Molecules (Basel, Switzerland). 2021;(24)
Abstract
The search for molecules that contribute to the relief of pain is a field of research in constant development. Lamiaceae is one of the most recognized families world-wide for its use in traditional medicine to treat diseases that include pain and inflammation. Mexico can be considered one of the most important centers of diversification, and due to the high endemism of this family, it is crucial for the in situ conservation of this family. Information about the most common genera and species found in this country and their uses in folk medicine are scarcely reported in the literature. After an extensive inspection in bibliographic databases, mainly Sciencedirect, Pubmed and Springer, almost 1200 articles describing aspects of Lamiaceae were found; however, 217 articles were selected because they recognize the Mexican genera and species with antinociceptive and/or anti-inflammatory potential to relieve pain, such as Salvia and Agastache. The bioactive constituents of these genera were mainly terpenes (volatile and non-volatile) and phenolic compounds such as flavonoids (glycosides and aglycone). The aim of this review is to analyze important aspects of Mexican genera of Lamiaceae, scarcely explored as a potential source of secondary metabolites responsible for the analgesic and anti-inflammatory properties of these species. In addition, we point out the possible mechanisms of action involved and the modulatory pathways investigated in different experimental models. As a result of this review, it is important to mention that scarce information has been reported regarding species of this family from Mexican genera. In fact, despite Calosphace being one of the largest subgenera of Salvia in the world, found mainly in Mexico, it has been barely investigated regarding its potential biological activities and recognized bioactive constituents. The scientific evidence regarding the different bioactive constituents found in species of Lamiaceae demonstrates that several species require further investigation in preclinical studies, and of course also in controlled clinical trials evaluating the efficacy and safety of these natural products to support their therapeutic potential in pain relief and/or inflammation, among other health conditions. Since Mexico is one of the most important centers of diversification, and due to the high endemism of species of this family, it is crucial their rescue, in situ conservation, and investigation of their health benefits.
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The Analgesic Properties of Corydalis yanhusuo.
Alhassen, L, Dabbous, T, Ha, A, Dang, LHL, Civelli, O
Molecules (Basel, Switzerland). 2021;(24)
Abstract
Corydalis yanhusuo extract (YHS) has been used for centuries across Asia for pain relief. The extract is made up of more than 160 compounds and has been identified as alkaloids, organic acids, volatile oils, amino acids, alcohols, and sugars. However, the most crucial biological active constituents of YHS are alkaloids; more than 80 have been isolated and identified. This review paper aims to provide a comprehensive review of the phytochemical and pharmacological effects of these alkaloids that have significant ties to analgesia.
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Neuropathic and Psychogenic Components of Burning Mouth Syndrome: A Systematic Review.
Orliaguet, M, Misery, L
Biomolecules. 2021;(8)
Abstract
The pathophysiology of primary burning mouth syndrome (BMS) has been extensively debated but is poorly understood despite a large number of hypotheses attempting to explain its etiopathogenic mechanisms. The aim of the present work was to systematically review papers that could provide arguments in favour of the neuropathic and psychogenic components of primary BMS for a better understanding of the disease. This systematic review (SR) was registered in PROSPERO (CRD42021224160). The search was limited to articles in English or French from 1990 to 01 December 2020. A total of 113 articles were considered for data extraction. We divided them into four subgroups: pharmacological and nonpharmacological management studies (n = 23); neurophysiological studies (n = 35); biohistopathological studies (n = 25); and questionnaire-based studies (n = 30). Several of these studies have shown neuropathic involvement at various levels of the neuraxis in BMS with the contribution of quantitative sensory testing (QST), functional brain imaging, and biohistopathological or pharmacologic studies. On the other hand, the role of psychological factors in BMS has also been the focus of several studies and has shown a link with psychiatric disorders such as anxiety and/or depression symptoms. Depending on the patient, the neuropathic and psychogenic components may exist simultaneously, with a preponderance of one or the other, or exist individually. These two components cannot be dissociated to define BMS. Consequently, BMS may be considered nociplastic pain.
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Clinical trials on pain lowering effect of ginger: A narrative review.
Rondanelli, M, Fossari, F, Vecchio, V, Gasparri, C, Peroni, G, Spadaccini, D, Riva, A, Petrangolini, G, Iannello, G, Nichetti, M, et al
Phytotherapy research : PTR. 2020;(11):2843-2856
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Abstract
Ginger has a pain-reducing effect and it can modulate pain through various mechanisms: inhibition of prostaglandins via the COX and LOX-pathways, antioxidant activity, inibition of the transcription factor nf-kB, or acting as agonist of vanilloid nociceptor. This narrative review summarizes the last 10-year of randomized controlled trials (RCTs), in which ginger was traditionally used as a pain reliever for dysmenorrhea, delayed onset muscle soreness (DOMS), osteoarthritis (AO), chronic low back pain (CLBP), and migraine. Regarding dysmenorrhea, six eligible studies suggest a promising effect of oral ginger. As concerned with DOMS, the four eligible RCTs suggested a reduction of inflammation after oral and topical ginger administration. Regarding knee AO, nine RCTs agree in stating that oral and topical use of ginger seems to be effective against pain, while other did not find significant differences. One RCT considered the use of ginger in migraine and suggested its beneficial activity. Finally, one RCT evaluated the effects of Swedish massage with aromatic ginger oil on CLBP demonstrated a reduction in pain. The use of ginger for its pain lowering effect is safe and promising, even though more studies are needed to create a consensus about the dosage of ginger useful for long-term therapy.
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Magnesium and Pain.
Shin, HJ, Na, HS, Do, SH
Nutrients. 2020;(8)
Abstract
In terms of antinociceptive action, the main mode of action of magnesium involves its antagonist action at the N-methyl-d-aspartate (NMDA) receptor, which prevents central sensitization and attenuates preexisting pain hypersensitivity. Given the pivotal function of NMDA receptors in pain transduction, magnesium has been investigated in a variety of pain conditions. The oral and parenteral administration of magnesium via the intravenous, intrathecal, or epidural route may alleviate pain and perioperative anesthetic and analgesic requirements. These beneficial effects of magnesium therapy have also been reported in patients with neuropathic pain, such as malignancy-related neurologic symptoms, diabetic neuropathy, postherpetic neuralgia, and chemotherapy-induced peripheral neuropathy. In addition, magnesium treatment is reportedly able to alleviate fibromyalgia, dysmenorrhea, headaches, and acute migraine attacks. Although magnesium plays an evolving role in pain management, better understanding of the mechanism underlying its antinociceptive action and additional clinical studies is required to clarify its role as an adjuvant analgesic.
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Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications.
Poggio, ED, McClelland, RL, Blank, KN, Hansen, S, Bansal, S, Bomback, AS, Canetta, PA, Khairallah, P, Kiryluk, K, Lecker, SH, et al
Clinical journal of the American Society of Nephrology : CJASN. 2020;(11):1595-1602
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Abstract
BACKGROUND AND OBJECTIVES Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This is a systematic review and meta-analysis of the literature published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta-analysis for proportions was used to obtain combined estimates of complication rates. Freeman-Tukey double-arcsine transformations were used to stabilize variance as complications were rare. RESULTS A total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%, bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of study type and geographic location. CONCLUSIONS Although the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after kidney biopsies of hospitalized patients with AKI.
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Tracking implementation strategies in the randomized rollout of a Veterans Affairs national opioid risk management initiative.
Rogal, SS, Chinman, M, Gellad, WF, Mor, MK, Zhang, H, McCarthy, SA, Mauro, GT, Hale, JA, Lewis, ET, Oliva, EM, et al
Implementation science : IS. 2020;(1):48
Abstract
BACKGROUND In 2018, the Department of Veterans Affairs (VA) issued Notice 2018-08 requiring facilities to complete "case reviews" for Veterans identified in the Stratification Tool for Opioid Risk Mitigation (STORM) dashboard as high risk for adverse outcomes among patients prescribed opioids. Half of the facilities were randomly assigned to a Notice version including additional oversight. We evaluated implementation strategies used, whether strategies differed by randomization arm, and which strategies were associated with case review completion rates. METHODS Facility points of contact completed a survey assessing their facility's use of 68 implementation strategies based on the Expert Recommendations for Implementing Change taxonomy. We collected respondent demographic information, facility-level characteristics, and case review completion rates (percentage of high-risk patients who received a case review). We used Kruskal-Wallis tests and negative binomial regression to assess strategy use and factors associated with case reviews. RESULTS Contacts at 89 of 140 facilities completed the survey (64%) and reported using a median of 23 (IQR 16-31) strategies. The median case review completion rate was 71% (IQR 48-95%). Neither the number or types of strategies nor completion rates differed by randomization arm. The most common strategies were using the STORM dashboard (97%), working with local opinion leaders (80%), and recruiting local partners (80%). Characteristics associated with case review completion rates included respondents being ≤ 35 years old (incidence rate ratio, IRR 1.35, 95% CI 1.09-1.67) and having < 5 years in their primary role (IRR 1.23; 95% CI 1.01-1.51), and facilities having more prior academic detailing around pain and opioid safety (IRR 1.40, 95% CI 1.12-1.75). Controlling for these characteristics, implementation strategies associated with higher completion rates included (1) monitoring and adjusting practices (adjusted IRR (AIRR) 1.40, 95% CI 1.11-1.77), (2) identifying adaptations while maintaining core components (AIRR 1.28, 95% CI 1.03-1.60), (3) conducting initial training (AIRR 1.16, 95% CI 1.02-1.50), and (4) regularly sharing lessons learned (AIRR 1.32, 95% CI 1.09-1.59). CONCLUSIONS In this national evaluation of strategies used to implement case reviews of patients at high risk of opioid-related adverse events, point of contact age and tenure in the current role, prior pain-related academic detailing at the facility, and four specific implementation strategies were associated with case review completion rates, while randomization to additional centralized oversight was not. TRIAL REGISTRATION This project is registered at the ISRCTN Registry with number ISRCTN16012111. The trial was first registered on May 3, 2017.
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Effect of nipple shield use on milk removal: a mechanistic study.
Coentro, VS, Perrella, SL, Lai, CT, Rea, A, Murray, K, Geddes, DT
BMC pregnancy and childbirth. 2020;(1):516
Abstract
BACKGROUND Concerns about reduced milk transfer with nipple shield (NS) use are based on evidence from studies with methodological flaws. Milk removal during breastfeeding can be impacted by infant and maternal factors other than NS use. The aim of this study was to control electric breast pump vacuum strength, pattern and duration across multiple study sessions to determine if NS use reduces milk removal from the breast. METHODS A within-subject study with two groups of breastfeeding mothers (infants < 6 months) were recruited; Control Group (CG): no breastfeeding difficulties; Pain Group (PG) used NS for persistent nipple pain. Mothers completed three randomised 15 min pumping sessions using the Symphony vacuum curve (Medela AG); no NS, fitted NS, and a small NS. Sessions were considered valid where the applied vacuum was within 20 mmHg of the set vacuum. Milk removal was considered as pumped milk volume, and also percentage of available milk removed (PAMR), which is calculated as the pumped volume divided by the estimated milk volume stored in the breast immediately prior to pumping. RESULTS Of 62 sessions (all: n = 31 paired sessions) a total of 11 paired sessions from both PG (n = 03) and CG (n = 08) were valid (subset) with and without a fitted NS. Only 2 small shield sessions were valid and so all small shield measurements were excluded. Both pumped volumes and PAMR were significantly lower with NS use for all data but not for subset data. (All: Volume and PAMR median: no NS: 76.5 mL, 69%, Fitted NS: 32.1 mL, 41% respectively (volume p = 0.002, PAMR p = 0.002); Subset: Volume and PAMR median: no NS: 83.8 mL, 72%; Fitted NS: 35.2 mL, 40% (volume p = 0.111 and PAMR p = 0.045). The difference in PAMR, but not volume, was statistically significant when analysed by linear mixed modelling. A decrease of 10 mmHg was associated with a 4.4% increase in PAMR (p = 0.017). CONCLUSIONS This experimental data suggests that nipple shield use may reduce milk removal. Close clinical monitoring of breastfeeding mothers using nipple shields is warranted.