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Firefighting Induces Acute Inflammatory Responses that are not Relieved by Aspirin in Older Firefighters.
Smith, DL, Friedman, NMG, Bloom, SI, Armero, WL, Pence, BD, Cook, MD, Fernhall, B, Horn, GP, Woods, J
Journal of occupational and environmental medicine. 2019;(7):617-622
Abstract
OBJECTIVE Sudden cardiac events account for 40% to 50% of firefighter line-of-duty deaths. Inflammatory proteins are strong biomarkers of cardiovascular inflammation. The present study investigated the effects of aspirin supplementation on inflammatory biomarkers following firefighting. METHODS Using a randomized, placebo-controlled, double-blind crossover design, 24 male firefighters (48.2 ± 5.9 years) were allocated into four conditions: acute (81 mg; single-dose) aspirin and placebo supplementation, and chronic (81 mg; 14 days) aspirin and placebo supplementation. Inflammatory proteins [interleukin (IL)-6, C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, P-selectin, matrix metalloproteinase-9 (MMP-9)] and antioxidant potential [total antioxidant capacity (TAC)] were measured pre- and post-structural firefighting drills. RESULTS Firefighting activities significantly increased IL-6, MMP-9, and P-Selectin; however, no changes in TAC and ICAM-1 were detected. Neither acute nor chronic aspirin supplementation attenuated this inflammatory response. CONCLUSION Firefighting significantly increases inflammatory biomarkers and neither acute nor chronic low-dose aspirin mitigates this response.
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Curcumin in Autoimmune and Rheumatic Diseases.
Yang, M, Akbar, U, Mohan, C
Nutrients. 2019;(5)
Abstract
Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement in clinical or laboratory outcomes. Three trials were in ulcerative colitis, two of which yielded significant improvement in at least one clinical outcome. Additionally, two clinical trials on rheumatoid arthritis, one clinical trial on lupus nephritis, and two clinical trials on multiple sclerosis resulted in inconclusive results. Longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long term benefits of curcumin supplementation. Multiple mechanisms of action of curcumin on these diseases have been researched, including the modulation of the eicosanoid pathway towards a more anti-inflammatory pathway, and the modulation of serum lipid levels towards a favorable profile. Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal-to-no side effects, which can be added in conjunction to current standard of care.
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Solid-state NMR analysis of crystalline and amorphous Indomethacin: An experimental protocol for full resonance assignments.
Lu, X, Xu, W, Hanada, M, Jermain, SV, Williams, RO, Su, Y
Journal of pharmaceutical and biomedical analysis. 2019;:47-55
Abstract
Solid-state NMR (ssNMR) analysis of pharmaceutical materials relies on accurate resonance assignments. The relatively low sensitivity and resolution from the natural abundance and solid-state nature of the active pharmaceutical ingredient (API) and particularly the disordered structure of amorphous forms result in the ambiguous identification of NMR peaks. In this study, a robust protocol for unambiguously assigning 13C and 1H chemical shifts of crystalline and amorphous APIs has been established and successfully tested on γ-polymorph indomethacin. Specifically, one-dimensional (1D) 13C-edited experiments, two-dimensional (2D) 13C-detected homo- and heteronuclear correlations, and 2D 1H-detected techniques under ultrafast magic angle spinning (MAS) provide enhanced resolution to identify overlapped 13C resonances and assign confidently the 1H chemical shifts. This experimental strategy allows us to assign particularly those carbons and protons either unassigned or ambiguous identified due to the technical challenges in previous literature. Besides, the chemical shift comparison between the crystalline and amorphous forms can potentially report the molecular packing variations.
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Analgesic efficacy of ketorolac associated with a tramadol/acetaminophen combination after third molar surgery - a randomized, triple-blind clinical trial.
Martins, LD, Rezende, M, Loguercio, AD, Bortoluzzi, MC, Reis, A
Medicina oral, patologia oral y cirugia bucal. 2019;(1):e96-e102
Abstract
BACKGROUND This study compared the efficacy of ketorolac alone versus its combination with tramadol/acetaminophen for pain control after mandibular third molar surgery. MATERIAL AND METHODS A randomized, triple-blind clinical trial was carried out with 52 patients divided into 2 groups: Group K+T+A (1 tablet of Ketorolac 10 mg plus and 1 capsule of Tramadol 37.5 mg/acetaminophen 325 mg) and Group K (1 tablet of Ketorolac 10 mg plus and 1 placebo capsule). The treatments were given 1 h before the surgery and was repeated 4 times per day, for 48 h. The difference in postoperative pain was assessed by 4 primary end-points: pain intensity (VAS 100mm, for 48 h), rescue medication, overall assessment and adverse effects. RESULTS Significant differences in pain intensity were observed in the different times (p < 0.05). The comparison of groups in each time showed significant differences only of 9 h, with lower level of pain intensity for group K+T+A (p = 0.005). The need of analgesics was higher in Group K (p < 0.001), the need of antiemetic were greater in Group K+T+A (p < 0.0001). No significant difference between groups were observed in overall assessment. The adverse effects was higher in Group K+T+A. CONCLUSIONS The current study showed that both ketorolac and the combination of ketorolac plus tramadol/acetaminophen showed good control of pain after the extraction of the lower third molars. Although the combination group showed lower pain at 9 h, the difference is small and not clinically relevant.
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A review of dexketoprofen trometamol in acute pain.
Hanna, M, Moon, JY
Current medical research and opinion. 2019;(2):189-202
Abstract
OBJECTIVE Dexketoprofen trometamol is a modified non-selective COX inhibitor with a rapid onset of action that is available as both oral and parenteral formulations. The aim of this narrative review was to assess the efficacy and tolerability/safety of dexketoprofen trometamol in acute pain states using the best available published scientific evidence (randomized controlled clinical trials and systematic reviews/meta-analyses). METHODS Literature retrieval was performed via Medline, Embase and the Cochrane Library (from inception up to March 2017) using combinations of the terms "randomized controlled trials", "dexketoprofen", "celecoxib", "etoricoxib", "parecoxib" and "acute pain". RESULTS Single-dose dexketoprofen trometamol provides effective analgesia in the treatment of acute pain, such as postoperative pain (dental and non-dental surgery), renal colic, acute musculoskeletal disorders and dysmenorrhea, and reduces opioid consumption in the postoperative setting. It has a rapid onset of action (within 30 minutes) and is well tolerated during short-term treatment. Direct comparisons with COX-2 inhibitors are lacking; however, the efficacy and tolerability of single-dose dexketoprofen trometamol appears to be consistent with that seen with celecoxib, etoricoxib and parecoxib in the acute pain setting. CONCLUSION In conclusion, dexketoprofen trometamol appears to provide similar analgesic efficacy to COX-2 inhibitors when used to treat acute pain, has a rapid onset of action, is well tolerated, and has an opioid-sparing effect when used as part of a multimodal regimen in the acute pain setting.
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Perioperative Opioid-sparing Strategies: Utility of Conventional NSAIDs in Adults.
Martinez, L, Ekman, E, Nakhla, N
Clinical therapeutics. 2019;(12):2612-2628
Abstract
PURPOSE Opioids have long been used to treat acute postsurgical and postprocedural pain; however, opioid-related adverse events (AEs) contribute to poor patient outcomes. In addition, perisurgical exposure to opioids can potentially increase the risk for opioid-use disorder. NSAIDs reduce pain and inflammation by a mechanism different from that of opioid analgesics and may be useful in reducing the need for opioid drugs as part of a multimodal analgesia strategy. We conducted this review to assess the effectiveness and tolerability of adjunctive conventional NSAIDs given systemically in the perioperative setting in terms of opioid-sparing effects observed postoperatively. METHODS Clinical trials published since 2000 that have assessed the opioid-sparing effects of conventional, nonselective NSAIDs were identified by a literature search using the PubMed search engine. Search terms were identified for the treatment of interest, the timing of the intervention, and the drugs of interest (NSAIDs). Data from studies that assessed opioid consumption outcomes with systemic NSAID administration were included in the review; data from studies in which NSAIDs were administered topically or via periarticular injection, local infiltration, or regional block were excluded. FINDINGS Upon full-text review of the search results, 32 studies were chosen for inclusion in this literature review. These studies included those that assessed diclofenac, ketorolac, ibuprofen, ketoprofen, dexketoprofen, flurbiprofen, lornoxicam, tenoxicam, meloxicam, and piroxicam. In studies in which NSAIDs were associated with opioid-sparing effects within the setting of patient-controlled analgesia, opioid use was reduced by 17%-∼50% with diclofenac, 9%-66% with ketorolac, 22%-46% with ibuprofen, 34%-66% with ketoprofen, 36%-50% with dexketoprofen, 38%-41% with tenoxicam, 36%-54% with lornoxicam, and ∼50% with flurbiprofen. No opioid-sparing effect was noted with meloxicam (1 study). The majority of studies that reported on pain-score changes revealed either pain reductions with NSAIDs versus placebo or similar pain scores between groups, indicating that NSAIDs did not compromise pain control. Although many studies found no difference in the prevalence of AEs in NSAID-treated patients compared with controls, several studies noted lower rates of nausea, vomiting, sedation, and pruritus with NSAIDs versus placebo. Conversely, NSAID-related AEs were few overall but included gastrointestinal bleeding, injection site reactions, transient oliguric renal failure, and dizziness. No surgery-related bleeding complications were observed. IMPLICATIONS NSAIDs have the potential to play an important role in reducing postoperative opioid requirements. Reducing the amount of opioids used could be expected to reduce opioid-related side effects and contribute to reversing the opioid epidemic.
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A comparative evaluation of transdermal diclofenac patch with oral diclofenac sodium as an analgesic drug following periodontal flap surgery: A randomized controlled clinical study.
Diwan, V, Srinivasa, TS, Ramreddy, KY, Agrawal, V, Nagdeve, S, Parvez, H
Indian journal of dental research : official publication of Indian Society for Dental Research. 2019;(1):57-60
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Abstract
BACKGROUND Pain is an inevitable outcome of any periodontal surgery. Controlling postoperative pain is of utmost importance so as to increase patient compliance. The present study aims to compare the degree of postoperative analgesia with the use of oral diclofenac sodium and transdermal diclofenac patch following periodontal flap surgery in patients with chronic periodontitis. MATERIALS AND METHODS A total of 20 patients requiring full mouth flap surgery were selected for this study. Flap surgery was performed quadrant-wise and transdermal diclofenac patch was applied on the right arm following surgery of one of the quadrants and 100 mg oral diclofenac sodium twice daily was prescribed following surgery of the subsequent quadrant. The postoperative pain was recorded on visual analog scale and pain intensity scale 24 h after the surgery. RESULTS Both the statistical and clinical observation showed that diclofenac sodium administered transdermally has equal efficacy as compared to drug administered orally. CONCLUSION The study concludes that the diclofenac administered transdermally has equal potency in relieving postoperative pain as compared to orally administered diclofenac sodium following modified flap surgery. Transdermal patch has an added advantage of better patient compliance as it does not cause gastric disturbance.
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Oral administration of nanomicelle curcumin in the prevention of radiotherapy-induced mucositis in head and neck cancers.
Delavarian, Z, Pakfetrat, A, Ghazi, A, Jaafari, MR, Homaei Shandiz, F, Dalirsani, Z, Mohammadpour, AH, Rahimi, HR
Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2019;(2):166-172
Abstract
UNLABELLED Oral mucositis (OM) is a complication of head and neck cancer (HNC) therapy with negative impact on the quality of life. Although definitive treatment has not yet been established, there is interest towards the use of natural compounds owing to their few side effects. Curcumin has a variety of biological and pharmacological properties including anticancer and anti-inflammatory effects. AIM: The aim of this study is to evaluate the effect of curcumin in the form of nanomicelle on OM in HNC patients receiving radiotherapy. METHODS In this clinical trial, 32 HNC patients were allocated to case and control groups, and respectively received nanocurcumin or placebo during radiotherapy. RESULTS We found a statistically significant difference in the severity of mucositis between the 2 groups at all visits. In contrast to the control-group patients, who all developed OM in the 2nd week of radiotherapy, only 32% of the case group developed OM with no obvious oral or systemic side effects. CONCLUSION Our data show that nanomicelle curcumin is an effective agent in the prevention of OM or reducing its severity. Thus, the administration of nanocurcumin can be considered as a reasonable approach to hinder the development of OM in HNC patients requiring radiotherapy.
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Irritable bowel syndrome and colonic diverticular disease: overlapping symptoms and overlapping therapeutic approaches.
Alamo, RZ, Quigley, EMM
Current opinion in gastroenterology. 2019;(1):27-33
Abstract
PURPOSE OF REVIEW Irritable bowel syndrome (IBS) is a common symptomatic disorder in the Western world and colonic diverticula are also prevalent; however, relationships between IBS-type symptoms and diverticula have been a source of much debate. Our goal was to reassess these relationships in the light of new data. RECENT FINDINGS On removing from consideration clinical scenarios which are directly related to diverticula (i.e., diverticulitis, diverticular hemorrhage, and complications of diverticulitis, such as stricture and fistula), relationships between IBS and diverticula can be seen to revolve around a number of questions. First, are IBS and symptomatic uncomplicated diverticular disease (SUDD) the same condition? Or, in other words is SUDD no more than IBS in an individual who just happens to have diverticula? Although coincident IBS and diverticula inevitably do occur there is some evidence to indicate that SUDD may be somewhat distinctive with SUDD being characterized by more frequent and severe pain. Second, and analogous to interactions between IBS and inflammatory bowel disease or celiac disease, can an episode of acute diverticulitis lead to the de novo development of IBS? There is now epidemiological and pathophysiological evidence to support this occurrence. SUMMARY Although relationships between uncomplicated diverticular disease and IBS have been reexamined their status remains unclear. As yet, however, none of the newer concepts related to this relationship have led to new therapeutic approaches in IBS or diverticular disease.
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INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease.
Meyer, PF, Tremblay-Mercier, J, Leoutsakos, J, Madjar, C, Lafaille-Magnan, ME, Savard, M, Rosa-Neto, P, Poirier, J, Etienne, P, Breitner, J, et al
Neurology. 2019;(18):e2070-e2080
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Abstract
OBJECTIVE To evaluate the safety and efficacy of low-dose naproxen for prevention of progression in presymptomatic Alzheimer disease (AD) among cognitively intact persons at risk. METHODS Investigation of Naproxen Treatment Effects in Pre-symptomatic Alzheimer's Disease (INTREPAD), a 2-year double-masked pharmaco-prevention trial, enrolled 195 AD family history-positive elderly (mean age 63 years) participants screened carefully to exclude cognitive disorder (NCT-02702817). These were randomized 1:1 to naproxen sodium 220 mg twice daily or placebo. Multimodal imaging, neurosensory, cognitive, and (in ∼50%) CSF biomarker evaluations were performed at baseline, 3, 12, and 24 months. A modified intent-to-treat analysis considered 160 participants who remained on-treatment through their first follow-up examination. The primary outcome was rate of change in a multimodal composite presymptomatic Alzheimer Progression Score (APS). RESULTS Naproxen-treated individuals showed a clear excess of adverse events. Among treatment groups combined, the APS increased by 0.102 points/year (SE 0.014; p < 10-12), but rate of change showed little difference by treatment assignment (0.019 points/year). The treatment-related rate ratio of 1.16 (95% confidence interval 0.64-1.96) suggested that naproxen does not reduce the rate of APS progression by more than 36%. Secondary analyses revealed no notable treatment effects on individual CSF, cognitive, or neurosensory biomarker indicators of progressive presymptomatic AD. CONCLUSIONS In cognitively intact individuals at risk, sustained treatment with naproxen sodium 220 mg twice daily increases frequency of adverse health effects but does not reduce apparent progression of presymptomatic AD. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that, for people who are cognitively intact, low-dose naproxen does not significantly reduce progression of a composite indicator of presymptomatic AD.