-
1.
Electroporation technique for joint pain - Pilot feasibility study on TMD patients.
Tartaglia, GM, Gizdulich, A, Farronato, M, Gupta, RJ, Connelly, ST
Clinical and experimental dental research. 2020;(6):642-649
-
-
Free full text
-
Abstract
OBJECTIVE(S): It is well appreciated that traditional analgesic delivery routes used to treat pain associated with temporomandibular disorder (TMD) often have harmful unintended side effects as a consequence of systemic distribution. Further, localized delivery of analgesic medication via intra-articular injections involves a different set of issues limiting their clinical viability. As an option, transdermal analgesic delivery provides for prolonged pain relief and flexibility in dose administration, while limiting systemic exposure and minimizing adverse events. Incorporation of a novel electroporation technique may further increase transdermal drug penetration into synovial tissue/fluid and enhance pain reduction. The present feasibility study compares the effectiveness of an electroporation-enhanced transdermal application of diclofenac sodium to a conventional intra-articular injection of triamcinolone acetonide suspension (corticosteroids) to treat patients with TMD associated pain. METHODS Pre- and post-treatment maximal incisal mouth opening (MIO), pain visual analog scale (VAS) and surface electromyography (EMG) of 22 patients treated with electroporation-enhanced diclofenac and 37 patients treated with corticosteroids injections were collected and analyzed. RESULTS In general, patients treated with electroporation exhibited better results in terms of pain improvement (corrected p-value = .01) compared to the standard treatment, but both methods were similarly effective for improvement of MIO (corrected p-value = .71) and improvement of all EMG indices (corrected p-values ≥ .05). CONCLUSION The enhancing effect of electroporation in transdermal delivery of diclofenac sodium was demonstrated by decreased pain, increase MIO and EMG improvement to normal values. Its analgesic and inflammatory results are comparable with standard treatment offered by corticosteroids.
-
2.
Cardiovascular safety of hydroxypropyl-β-cyclodextrin-diclofenac in the management of acute postsurgical pain: a pooled analysis of 2 randomized, double-blind, placebo- and active comparator-controlled phase III clinical trials.
Gan, TJ, Singla, N, Daniels, SE, Lacouture, PG, Min, LH, Reyes, CR, Carr, DB
Journal of clinical anesthesia. 2016;:249-58
Abstract
STUDY OBJECTIVE Long-term use of nonsteroidal anti-inflammatory drugs, including selective and nonselective cyclooxygenase inhibitors, has been suggested to be associated with cardiovascular (CV) safety risks. Data are limited regarding CV risks associated with short-term nonsteroidal anti-inflammatory drug use, including injectable formulations, although it has been suggested that even a single dose may increase CV adverse event (AE) risk. The objective of this study was to examine the CV safety of an injectable diclofenac formulation solubilized with hydroxypropyl-β-cyclodextrin (HPβCD) when given for ≤5days postoperatively. DESIGN A pooled analysis of CV AEs from 2 pivotal phase III clinical trials examining the efficacy and safety of intravenous (IV) HPβCD-diclofenac vs placebo and the active comparator ketorolac was conducted. SETTING Postoperative, with treatment initiated in the postanesthesia care unit ≤6hours postsurgery. PATIENTS Overall, 608 abdominal/pelvic and orthopedic surgery patients met inclusion criteria and received ≥1 study medication dose. INTERVENTIONS Patients received either HPβCD-diclofenac, ketorolac, or placebo via IV bolus injection every 6hours, for ≤5days postsurgery. MEASUREMENTS CV AEs, reported by study investigators, were evaluated through the treatment period and follow-up (≤37days after last study medication dose), and relative CV AE risks were estimated. MAIN RESULTS IV HPβCD-diclofenac was not associated with increased treatment-emergent CV AE incidence vs placebo (11.6% vs 12.2%; relative risk, 0.96 [95% confidence interval, 0.56-1.62]). Serious CV AEs as well as treatment-related AEs were uncommon, and there were no reports of myocardial infarction or cerebrovascular accident. CV AEs were uncommon during the follow-up period, occurring in 1.3%, 0%, and 1.4% of patients in the HPβCD-diclofenac, ketorolac, and placebo groups, respectively. CONCLUSIONS Although a longer duration follow-up study in a larger patient population would expand our understanding of potential CV risks, the present analysis suggests that postoperative use of HPβCD-diclofenac does not present an added CV safety risk over placebo.
-
3.
The diameter response of retinal arterioles in diabetic maculopathy is reduced during hypoxia and is unaffected by the inhibition of cyclo-oxygenase and nitric oxide synthesis.
Petersen, L, Bek, T
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2016;(12):2339-2346
Abstract
PURPOSE Diabetic retinopathy is accompanied with changes in the diameter regulation and oxygenation of retinal vessels. Previous studies have shown that in normal persons and in diabetic patients without retinopathy hypoxia-induced vasodilatation is mediated by cyclo-oxygenase (COX) products and nitric oxide (NO). The purpose of the present study was to study whether these effects can be reproduced in patients with diabetic maculopathy. METHODS Eighteen patients with diabetic maculopathy aged 29-57 years were examined using the Dynamic Vessel Analyzer. The resting diameter and the diameter changes of retinal arterioles during isometric exercise and flicker stimulation were studied before and during breathing a hypoxic gas mixture. The examinations were also performed before and during intravenous infusion of the NOS inhibitor L-NMMA, and were repeated on a second day after topical administration of the COX-inhibitor diclofenac. RESULTS The diameter of retinal arterioles showed no significant change during hypoxia or L-NMMA infusion, or after topical application of diclofenac (p > 0.25 for all comparisons). The resting diameter of the venules was significantly increased during hypoxia (p = 0.003) and decreased during L-NMMA infusion (p < 0.0001). The diameter of retinal venules during isometric exercise increased significantly during hypoxia (p = 0.01). Flicker stimulation induced significant dilatation of the venules, which was significantly reduced during hypoxia and increased during L-NMMA infusion (p < 0.0001 for all comparisons). CONCLUSION Hypoxia-induced dilatation of retinal arterioles is severely reduced in patients with diabetic maculopathy. Future intervention studies aimed at normalizing the diameter regulation of retinal arterioles in diabetic patients should preferentially be conducted in the early stages of the disease where the potential for changing the vessel diameter is preserved. ClinicalTrials.gov identifier: NCT01689090.
-
4.
Topical Fluorometholone Versus Diclofenac Sodium in Cases With Perennial Allergic Conjunctivitis.
Li, Z, Chen, W, Zhang, Y, Jhanji, V, Fan, Z, Mu, G
Eye & contact lens. 2015;(5):310-3
Abstract
PURPOSE To compare the efficacy of diclofenac sodium (DS) 0.1% and fluorometholone (FL) 0.1% in patients with perennial allergic conjunctivitis. METHODS Fluorometholone 0.1% or DS 0.1% eye drops were topically administrated 4 times daily for 4 weeks in patients with perennial allergic conjunctivitis. Assessment was conducted with a 4-point rating scale (0=none, 1=mild, 2=moderate, and 3=severe) for 4 signs and 5 symptoms. RESULTS Two hundred sixty-one patients were recruited. The demographics and baseline skin prick scores between both groups were comparable. Mean baseline scores in DS and FL group were 6.77 ± 2.24 and 6.34 ± 2.10, respectively. The scores rapidly decreased to 3.28 ± 1.47 and 2.69 ± 1.44 on day 7. Diclofenac sodium expressed a slower effect compared with FL within the first 3 days of treatment (P=0.01). CONCLUSIONS The efficacy of topical FL and DS was comparable for the management of cases with perennial allergic conjunctivitis. However, FL led to a more rapid alleviation of signs and symptoms as compared with DS in early days after the initiation of treatment.
-
5.
Efficacy and safety of low dose subcutaneous diclofenac in the management of acute pain: a randomized double-blind trial.
Dietrich, T, Leeson, R, Gugliotta, B, Petersen, B
Pain practice : the official journal of World Institute of Pain. 2014;(4):315-23
Abstract
OBJECTIVE Diclofenac is an effective and well-tolerated nonsteroidal anti-inflammatory drug (NSAID) frequently used in the treatment of acute pain. Marketed formulations for parenteral administration usually contain 75 mg/3 mL of diclofenac sodium, which provide limited dosing flexibility, and are usually given intramuscularly. METHODS We present a randomized, double-blind, active comparator- and placebo-controlled, parallel-group phase III multicenter study, investigating efficacy and tolerability of a new 1 mL-volume formulation of diclofenac sodium (25, 50 or 75 mg) containing hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer. This low-volume formulation allows subcutaneous (SC), in addition to intramuscular (IM) administration. Patients developing moderate-to-severe pain (≥ 50 mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25 mg diclofenac HPβCD (n = 77), 50 mg diclofenac HPβCD (n = 76), 75 mg diclofenac HPβCD (n = 78), or placebo (n = 75). RESULTS Mean pain intensity difference at 1.5 hours postdose (primary endpoint) was higher in all diclofenac-treated groups than placebo group. The adjusted means (95% CI) were 36.5 (31.7 to 41.2) in diclofenac 25 mg group, 37.3 (32.6 to 42.1) in diclofenac 50 mg group, 37.7 (33.0 to 42.4) in diclofenac 75 mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50 mg doses of diclofenac produced significantly greater pain relief than placebo (P < 0.001 in both comparisons). CONCLUSION Single SC doses of diclofenac HPβCD of 25 and 50 mg are effective and well tolerated for relieving pain compared with placebo.
-
6.
Evaluating the effects of diclofenac sodium and etodolac on renal hemodynamics with contrast-enhanced ultrasonography: a pilot study.
Imamura, H, Hata, J, Iida, A, Manabe, N, Haruma, K
European journal of clinical pharmacology. 2013;(2):161-5
Abstract
PURPOSE Contrast-enhanced ultrasonography (CEUS) is a novel approach used for measuring organ perfusion changes. Studies using CEUS to assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on renal blood flow (RBF) have not yet been conducted. We aimed to evaluate the effects of NSAIDs on the renal hemodynamics of healthy subjects with CEUS. METHODS We performed CEUS using the bolus injection method in a total of 10 healthy subjects. Measurements were completed over two study days in a randomized, crossover manner. On each study day, CEUS was performed twice, before and after the administration of NSAIDs. Subjects received an injection of contrast medium and images were recorded. A region-of-interest (ROI) was selected within the renal cortex, signal intensity in the ROI of the kidney was measured and a time-intensity curve (TIC) was automatically generated with attached software. RESULTS The mean (±SD) peak intensity decreased significantly after an administration of diclofenac sodium (from 26.0 × 10(-4) ± 17.4 × 10(-4) AU to 19.2 × 10(-4) ± 12.0 × 10(-4) AU; P = 0.022), but not significantly with etodolac (from 26.5 × 10(-4) ± 9.7 × 10(-4) AU to 25.9 × 10(-4) ± 20.8 × 10(-4) AU; P = 0.474). The mean (±SD) percent reduction in intensity following diclofenac sodium administration was significantly reduced compared with etodolac administration (22.2 ± 20.5 % vs. 3.4 ± 8.9 %, P = 0.037). CONCLUSIONS These finding suggests that diclofenac sodium (P = 0.022), but not etodolac (P = 0.474), affects renal hemodynamics even in healthy subjects.
-
7.
Effectiveness of lumbar zygapophysial joint blockage for low back pain.
Celik, B, Er, U, Simsek, S, Altug, T, Bavbek, M
Turkish neurosurgery. 2011;(4):467-70
Abstract
AIM: Zygapophysial joints have been a well-recognized source of low back pain. This paper compares the efficacy of lumbar zygapophysial joints blockage and medical therapy in terms of pain relief, loss of working days and recurrence of pain in a population with mechanical low back pain. MATERIAL AND METHODS 80 patients suffering from low back pain were included in the study. Patients were divided into 2 groups. Patients in Group I were given diclofenac sodium, thiocolchicoside and were recommended bed rest. Patients in Group II received zygapophysial joints blockage by prilocaine, bupivacaine and methylprednisolone acetate. Both of the groups were evaluated with a Oswestry low back pain disability questionnaire and visual analog scale for pain. RESULTS Posttreatment VAS and ODQ scores were significantly lower than pretreatment scores. The decrease in these scores in Group II was greater than those of Group I. CONCLUSION Blockage of the lumbar facet joints is a rapid and effective way to reduce pain originating from lumbar facet joints.
-
8.
Effects of non-steroidal anti-inflammatory drugs (NSAIDs) on serum allergen levels after wheat ingestion.
Matsuo, H, Kaneko, S, Tsujino, Y, Honda, S, Kohno, K, Takahashi, H, Mihara, S, Hide, M, Aburatani, K, Honjoh, T, et al
Journal of dermatological science. 2009;(3):241-3
-
9.
Treatments with losartan or enalapril are equally sensitive to deterioration in renal function from cyclooxygenase inhibition.
Juhlin, T, Erhardt, LR, Ottosson, H, Jönsson, BA, Höglund, P
European journal of heart failure. 2007;(2):191-6
Abstract
BACKGROUND The beneficial effects of angiotensin converting enzyme (ACE)-inhibitors are in part mediated through the inhibition of the degradation of the vasodilator bradykinin. The bradykinin effect is counteracted by cyclooxygenase-inhibitors. Angiotensin receptor blockers (ARBs) do not affect bradykinin. AIMS To test the hypothesis that renal counteraction from a cyclooxygenase-inhibitor, diclofenac, is different in subjects treated with an ACE-inhibitor, enalapril compared with an ARB, losartan. METHODS Twelve elderly, healthy, slightly over-hydrated subjects received diclofenac orally after pre-treatment with a diuretic, bendroflumethiazide, and enalapril or bendroflumethiazide and losartan, in a double-blind cross-over fashion, with a wash-out period of at least 1 week. RESULTS Diclofenac reduced GFR significantly from 81(64-98) ml/min at first observations after dose for enalapril to 29(16-42) and from 76(64-88) after losartan to 35(24-46). There was no significant difference between enalapril and losartan in GFR. Diclofenac induced decreases in urine flow, excretion rates and clearances of sodium, osmolality clearance and free water clearance, irrespective of treatment with enalapril or losartan. However, serum potassium and handling of potassium were significantly lower after losartan-treatment. CONCLUSION The negative renal effects of diclofenac administration in subjects with activation of the renin-angiotensin system and enalapril treatment are the same in subjects with activation of the renin-angiotensin system and losartan treatment.
-
10.
Effect of adjunctive diclofenac with verteporfin therapy to treat choroidal neovascularization due to age-related macular degeneration: phase II study.
, , Boyer, DS, Beer, PM, Joffe, L, Koester, JM, Marx, JL, Weisberger, A, Yoser, SL
Retina (Philadelphia, Pa.). 2007;(6):693-700
Abstract
BACKGROUND To determine short-term effects of topical diclofenac administered in conjunction with verteporfin therapy for predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS Randomized, multicenter (14), prospective, placebo-controlled, double-masked clinical trial. Patients (n=61) were randomly assigned to treatment with diclofenac sodium ophthalmic solution 0.1% or placebo and followed for 12 weeks. Patients instilled diclofenac or placebo two drops four times daily, 2-4 days before verteporfin treatment until 2 weeks after treatment, then two drops twice daily for 10 weeks. This exploratory study was not powered to detect differences between treatment groups. Statistical analyses were conducted solely to aid interpretation of results. RESULTS In diclofenac-treated eyes, mean changes in visual acuity letter score from baseline in the diclofenac and placebo groups were +1.8 letters and -1.0 at week 1 (P=0.505 between groups). Mean visual acuity letter scores decreased in both groups at all subsequent visits, with a mean change at 12 weeks of -7.4 with diclofenac and -2.6 with placebo (P=0.213). Percentages of eyes with stable or improved vision (change or=5 letters) were similar in the diclofenac and placebo groups at all study visits. No significant between-group differences in changes from baseline in lesion area, greatest linear dimension (GLD), fluorescein leakage, or retinal thickness were detected. CONCLUSION In patients with predominantly classic subfoveal CNV due to AMD, administration of topical diclofenac with verteporfin therapy was associated with similar vision outcomes to placebo plus verteporfin therapy.