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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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The effect of aromatherapy with rose and lavender on anxiety, surgical site pain, and extubation time after open-heart surgery: A double-center randomized controlled trial.
Babatabar Darzi, H, Vahedian-Azimi, A, Ghasemi, S, Ebadi, A, Sathyapalan, T, Sahebkar, A
Phytotherapy research : PTR. 2020;(10):2675-2684
Abstract
To determine the effect of aromatherapy with rose and lavender on the patient outcomes after open-heart surgery (OHS). In the clinical trial, patients were randomized to four groups. One group received routine care, the placebo group received a cotton swab soaked in water and the other two groups received either a cotton swab containing three drops of rose or lavender essence (0.2 ml). A total of 160 patients were randomized into four groups. Intergroup anxiety was not significantly different; however, the reciprocal time-group effect was significant among the four groups. The extubation time was significant among the four groups which related to rose essence group compared with the control group (p < .001) and placebo group (p = .029). The surgical site pain was significant in the rose essence and lavender groups compared to the control group. Aromatherapy can reduce extubation time, surgical site pain severity, and anxiety in patients undergoing OHS.
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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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The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in Individuals with Knee Osteoarthritis.
Strath, LJ, Jones, CD, Philip George, A, Lukens, SL, Morrison, SA, Soleymani, T, Locher, JL, Gower, BA, Sorge, RE
Pain medicine (Malden, Mass.). 2020;(1):150-160
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Abstract
OBJECTIVE Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the efficacy of a dietary intervention to reduce KOA. DESIGN A randomized controlled pilot study to test the efficacy of two dietary interventions. SUBJECTS Adults 65-75 years of age with KOA. METHODS Participants were asked to follow one of two dietary interventions (low-carbohydrate [LCD], low-fat [LFD]) or continue to eat as usual (control [CTRL]) over 12 weeks. Functional pain, self-reported pain, quality of life, and depression were assessed every three weeks. Serum from before and after the diet intervention was analyzed for oxidative stress. RESULTS Over a period of 12 weeks, the LCD reduced pain intensity and unpleasantness in some functional pain tasks, as well as self-reported pain, compared with the LFD and CTRL. The LCD also significantly reduced oxidative stress and the adipokine leptin compared with the LFD and CTRL. Reduction in oxidative stress was related to reduced functional pain. CONCLUSIONS We present evidence suggesting that oxidative stress may be related to functional pain, and lowering it through our LCD intervention could provide relief from pain and be an opioid alternative.
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Safety, Tolerability, and Pharmacokinetics of GDC-0276, a Novel NaV1.7 Inhibitor, in a First-in-Human, Single- and Multiple-Dose Study in Healthy Volunteers.
Rothenberg, ME, Tagen, M, Chang, JH, Boyce-Rustay, J, Friesenhahn, M, Hackos, DH, Hains, A, Sutherlin, D, Ward, M, Cho, W
Clinical drug investigation. 2019;(9):873-887
Abstract
BACKGROUND AND OBJECTIVE Current pain therapies often do not provide adequate pain relief and have dose-limiting adverse effects. Genetic evidence indicates that NaV1.7 sodium channels are required for pain transduction and therefore represent an important therapeutic target. GDC-0276 is a novel NaV1.7 inhibitor developed for the treatment of pain. This first-in-human trial evaluated the safety, tolerability, and pharmacokinetics of orally administered GDC-0276 in healthy subjects. METHODS This phase I, randomized, double-blind, placebo-controlled study assessed GDC-0276 as powder-in-capsule (PIC) or cyclodextrin solution (CD) single doses (SDs) of 2-270 mg (seven cohorts) and 45-540 mg (five cohorts), respectively. Multiple (MD) PIC doses were administered as total daily doses of 15-540 mg divided into two or three doses/day, up to 10 or 14 days. Safety was assessed by monitoring adverse events (AEs), vital signs, physical examinations, electrocardiograms, and laboratory tests for up to 15 days after the last day of dosing. GDC-0276 plasma pharmacokinetics were also determined. RESULTS Three stages included 183 randomized subjects. GDC-0276 plasma exposure increased with dose level for all stages. Exposure was higher in the SD-CD cohorts compared with the equivalent SD-PIC dose levels. SDs were adequately tolerated up to 270 mg (SD-PIC) and 360 mg (SD-CD). Hypotension limited tolerability in the 540-mg SD-CD cohort. Multiple PIC doses were tolerated up to 270 mg twice daily, however liver transaminase elevations were frequently observed. No deaths or serious AEs occurred. CONCLUSION GDC-0276 exhibited a safety and pharmacokinetic profile that supports its future investigation as a potential therapeutic for pain.
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Phonopheresis Associated with Nanoparticle Gel from Phyllanthus amarus Relieves Pain by Reducing Oxidative Stress and Proinflammatory Markers in Adults with Knee Osteoarthritis.
Decha, P, Kanokwan, K, Jiraporn, T, Pichaya, J, Pisittawoot, A
Chinese journal of integrative medicine. 2019;(9):691-695
Abstract
OBJECTIVE To determine the changes in serum levels of inflammatory biomarkers and antioxidant levels among the knee osteoarthritis (OA) patients after treatment with Phyllanthus amarus (PP) by nanoparticle gel phonophoresis. METHODS This study was a randomized, double-blind, placebo-control, parallel-group, clinical trial involving 30 subjects with mild-to-moderate degree of knee OA. The patients were allocated to two groups using a computer-generated random numbers, and received conventional ultrasound therapy (control group, 15 cases) and PP (treatment group, 15 cases) once daily for 10 sessions. The pain was evaluated by visual analogue scale (VAS). Serum levels of tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbnent assay (ELISA). Nitric oxide (NO) was determined by modified Griess reagent. The antioxidant effects, including superoxide dismutase (SOD) and total antioxidant capacity (TAC), were also measured by ELISA assay. RESULTS The VAS score was significantly decreased in the treatment group compared with the control group after treatment (P<0.01). The serum concentrations of TNF-α and NO were significantly reduced in the treatment group compared with the control group (P<0.01) after treatment. However, the serum concentrations of SOD and TAC in the treatment group were significantly higher after treatment compared with the control group (P<0.01). CONCLUSION PP could alleviate knee pain and significantly reduce systemic anti-inflammatory effects in knee OA patients.
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Efficacy of Plantago major, chlorhexidine 0.12% and sodium bicarbonate 5% solution in the treatment of oral mucositis in cancer patients with solid tumour: A feasibility randomised triple-blind phase III clinical trial.
Cabrera-Jaime, S, Martínez, C, Ferro-García, T, Giner-Boya, P, Icart-Isern, T, Estrada-Masllorens, JM, Fernández-Ortega, P
European journal of oncology nursing : the official journal of European Oncology Nursing Society. 2018;:40-47
Abstract
PURPOSE Oral mucositis is one of the most common adverse effects of chemotherapy and radiotherapy. The aim of this study was to compare the efficacy of Plantago major extract versus chlorhexidine 0.12% versus sodium bicarbonate 5% in the symptomatic treatment of chemotherapy-induced oral mucositis in solid tumour cancer patients. METHOD Multicentre randomised controlled trial estimated sample of 45 solid tumour patients with grade II-III mucositis. The participants were randomised to one of three treatments, consisting of sodium bicarbonate 5% aqueous solution together with: an additional dose of sodium bicarbonate 5% aqueous solution, Plantago major extract, or chlorhexidine 0.12%. The primary outcomes were severity of mucositis, pain intensity, oral intake capacity and quality of life. The independent variable was treatment group, and confounders included sociodemographic data, neutrophil count, chemotherapy drug and dose received. RESULTS Of the 50 patients enrolled, 68% (n = 34) achieved grade 0 mucositis (none), with those using the double sodium bicarbonate rinse healing in five days on average (95% CI 3.9, 6.5) versus seven days (95% CI 5.3, 9,0) for the chlorhexidine group and seven days (95% CI 5.3, 8.5) for the Plantago major group. The pain experienced by the participants lessened over the 14 days of treatment, but differences in pain intensity between the three groups did not show statistical significance (p = 0.762). CONCLUSIONS Healing time was shorter with the double sodium bicarbonate solution compared to the other two rinses, but the differences were not significant. Our results suggest it may be time to reconsider the use of Plantago major extract in the management of oral mucositis.
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Randomised crossover trial showed that using breast milk or sucrose provided the same analgesic effect in preterm infants of at least 28 weeks.
Collados-Gómez, L, Ferrera-Camacho, P, Fernandez-Serrano, E, Camacho-Vicente, V, Flores-Herrero, C, García-Pozo, AM, Jiménez-García, R
Acta paediatrica (Oslo, Norway : 1992). 2018;(3):436-441
Abstract
AIM: Repeated, ongoing exposure to pain influences the growth, cognitive and motor functions, behaviour, personality and neurodevelopment of preterm infants. We compared the analgesic effects of expressed breast milk (EBM) and 24% oral sucrose on preterm neonates during venipuncture. METHODS This multicentre randomised, noninferiority, crossover trial focused on five neonatal university units in Madrid, Spain, from October 2013 to October 2014. It comprised 66 preterm infants born at less than 37 weeks and randomly split into two groups. They received either EBM or sucrose two minutes before venepuncture, together with nonnutritive sucking and swaddling, then the opposite procedure at a later point. Pain was measured with the premature infant pain profile (PIPP) and crying was also measured. RESULTS There were no statistically significant differences between the groups. The PIPP scores were seven (4-9) with breast milk and six (4-8.25) with sucrose (p = 0.28). The 11 infants born at under 28 weeks of age showed higher median scores of nine (9-14) for breast milk and four (4-7) for sucrose (p = 0.009). CONCLUSION EBM and 24% sucrose had the same analgesic effect during venipuncture in most of the preterm neonates, but sucrose worked better in extremely preterm infants.
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PASCAL laser platform produces less pain responses compared to conventional laser system during the panretinal photocoagulation: a randomized clinical trial.
Inan, S, Polat, O, Yıgıt, S, Inan, UU
African health sciences. 2018;(4):1010-1017
Abstract
BACKGROUND Most of patients experience pain during the panretinal photocoagulation(PRP). Laser photocoagulation delivery has advanced with the introduction of pattern-scanning laser systems (PASCAL). Shorter pulse duration and less choroidal penetration believed to reduce pain during the laser treatment. OBJECTIVES To compare the severity of expressed pain scores in patients with PDR who underwent PRP either with PASCAL laser or conventional laser. METHODS A total of 28 patients with a diagnosis of PDR who were scheduled for bilateral PRP therapy were enrolled into the prospective study. Both eyes were treated within the same session and while one eye was treated with PASCAL the other was treated with conventional laser randomly. Pulse duration was adjusted to 100-ms in conventional laser and 30 ms in PASCAL. The severity of pain was graded using a verbal scale and a visual analog scale (VAS). RESULTS Mean age was 61.36±9.10 years. Mean verbal and VAS scores were 1.32±0.47 and 2.86±1.21 in the PASCAL laser and 2.39±0.49 and 5.75±1.35 in the conventional laser group, respectively. Differences between expressed pain scores obtained by both two scales were statistically significant (p<0.001). CONCLUSION PASCAL laser significantly alleviates pain levels possibly due to the shorter laser pulse duration and lower intensity.