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1.
Nonopioid, Multimodal Analgesia as First-line Therapy After Otolaryngology Operations: Primer on Nonsteroidal Anti-inflammatory Drugs (NSAIDs).
Cramer, JD, Barnett, ML, Anne, S, Bateman, BT, Rosenfeld, RM, Tunkel, DE, Brenner, MJ
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2021;(4):712-719
Abstract
OBJECTIVE To offer pragmatic, evidence-informed advice on nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy after surgery. This companion to the American Academy of Otolaryngology-Head & Neck Surgery (AAO-HNS) clinical practice guideline (CPG), "Opioid Prescribing for Analgesia After Common Otolaryngology Operations," presents data on potency, bleeding risk, and adverse effects for ibuprofen, naproxen, ketorolac, meloxicam, and celecoxib. DATA SOURCES National Guidelines Clearinghouse, CMA Infobase, National Library of Guidelines, NICE, SIGN, New Zealand Guidelines Group, Australian National Health and Medical, Research Council, TRIP database, PubMed, Guidelines International Network, Cochrane Library, EMBASE, CINAHL, BIOSIS Previews, ISI Web of Science, AHRQ, and HSTAT. REVIEW METHODS AAO-HNS opioid CPG literature search strategy, supplemented by PubMed/MEDLINE searches on NSAIDs, emphasizing systematic reviews and randomized controlled trials. CONCLUSION NSAIDs provide highly effective analgesia for postoperative pain, particularly when combined with acetaminophen. Inconsistent use of nonopioid regimens arises from common misconceptions that NSAIDs are less potent analgesics than opioids and have an unacceptable risk of bleeding. To the contrary, multimodal analgesia (combining 500 mg acetaminophen and 200 mg ibuprofen) is significantly more effective analgesia than opioid regimens (15 mg oxycodone with acetaminophen). Furthermore, selective cyclooxygenase-2 inhibition reliably circumvents antiplatelet effects. IMPLICATIONS FOR PRACTICE The combination of NSAIDs and acetaminophen provides more effective postoperative pain control with greater safety than opioid-based regimens. The AAO-HNS opioid prescribing CPG therefore prioritizes multimodal, nonopioid analgesia as first-line therapy, recommending that opioids be reserved for severe or refractory pain. This state-of-the-art review provides strategies for safely incorporating NSAIDs into acute postoperative pain regimens.
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2.
Breaking the therapeutic ceiling in drug development in ulcerative colitis.
Alsoud, D, Verstockt, B, Fiocchi, C, Vermeire, S
The lancet. Gastroenterology & hepatology. 2021;(7):589-595
Abstract
Increased knowledge of the intricate pathogenesis of ulcerative colitis has triggered an advance in drug development during the past two decades, resulting in the advent of several biological agents and small-molecule therapies. Although the increase in therapeutic options is positive, remission rates of patients with ulcerative colitis given new therapeutic agents in induction trials remain at a modest 20-30%, seemingly facing a so-called therapeutic ceiling. This therapeutic ceiling requires a critical appraisal and highlights the need for alternative strategies for drug development. In this Review, we objectively itemise the boundaries of therapeutic efficacy in ulcerative colitis, provide possible explanations for the shortcomings of current strategies, and propose solutions to achieve better therapeutic outcomes in ulcerative colitis.
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3.
Early use of non-steroidal anti-inflammatory drugs in COVID-19 might reverse pathogenesis, prevent complications and improve clinical outcomes.
Kelleni, MT
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;:110982
Abstract
The pathogenesis of Coronavirus disease 2019 is still obscure and the need for exploration of possible mechanisms to suggest drugs based on knowledge should never be delayed. In this manuscript, we present a novel theory to explain the pathogenesis of COVID-19; lymphocyte distraction theory upon which the author has used, in a preprinted protocol, non-steroidal anti-inflammatory drugs (NSAIDs); diclofenac potassium, ibuprofen and ketoprofen, successfully to treat COVID-19 patients. Furthermore, we agree with a recommendation that glucocorticoids should not be used routinely for COVID-19 patients and suggested to be beneficial only for patients with late acute respiratory distress syndrome. A clinical proof of ibuprofen safety in COVID-19 has been published by other researchers and we suggest that early administration of NSAIDs, including ibuprofen, in COVID-19 is not only safe but it might also prevent COVID-19 complications and this manuscript explains some of the suggested associated protective mechanisms.
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4.
Are NSAIDs Safe? Assessing the Risk-Benefit Profile of Nonsteroidal Anti-inflammatory Drug Use in Postoperative Pain Management.
Chang, RW, Tompkins, DM, Cohn, SM
The American surgeon. 2021;(6):872-879
Abstract
In this article, we review controversies in assessing the risk of serious adverse effects caused by administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Our focus is upon NSAIDs used in short courses for the management of acute postoperative pain. In our review of the literature, we found that the risks of short-term NSAID use may be overemphasized. Specifically, that the likelihood of renal dysfunction, bleeding, nonunion of bone, gastric complications, and finally, cardiac dysfunction do not appear to be significantly increased when NSAIDs are used appropriately after surgery. The importance of this finding is that in light of the opioid epidemic, it is crucial to be aware of alternative analgesic options that are safe for postoperative pain control.
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5.
Effects of curcumin on mitochondria in neurodegenerative diseases.
Bagheri, H, Ghasemi, F, Barreto, GE, Rafiee, R, Sathyapalan, T, Sahebkar, A
BioFactors (Oxford, England). 2020;(1):5-20
Abstract
Neurodegenerative diseases (NDs) result from progressive deterioration of selectively susceptible neuron populations in different central nervous system (CNS) regions. NDs are classified in accordance with the primary clinical manifestations (e.g., parkinsonism, dementia, or motor neuron disease), the anatomic basis of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), and fundamental molecular abnormalities (e.g., mutations, mitochondrial dysfunction, and its related molecular alterations). NDs include the Alzheimer disease and Parkinson disease, among others. There is a growing evidence that mitochondrial dysfunction and its related mutations in the form of oxidative/nitrosative stress and neurotoxic compounds play major roles in the pathogenesis of various NDs. Curcumin, a polyphenol and nontoxic compound, obtained from turmeric, has been shown to have a therapeutic beneficial effect in various disorders especially on the CNS cells. It has been shown that curcumin has considerable neuro- and mitochondria-protective properties against broad-spectrum neurotoxic compounds and diseases/injury-associating NDs. In this article, we have reviewed the various effects of curcumin on mitochondrial dysfunction in NDs.
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6.
Strategies of analgesic treatment after cesarean delivery. Current state and new alternatives.
Arroyo-Fernández, FJ, Calderón Seoane, JE, Torres Morera, LM
Revista espanola de anestesiologia y reanimacion. 2020;(3):167-175
Abstract
The number of caesarean sections performed worldwide is increasing, and with it, the need for the optimal analgesia strategies. Deficient postoperative analgesia increases the need for opioids, delays recovery, and is associated with chronic pain and postpartum depression. It is essential to find good postoperative pain control strategies that facilitate early mobility, early recovery, and early hospital discharge with minimal side effects on the mother and infant. Multimodal analgesia based on neuroaxial anaesthesia with morphine in combination with non-opioids such as non-steroidal anti-inflammatory drugs and paracetamol, gives the best post-caesarean analgesia outcome, and allows anaesthesiologists to reserve opioids, corticoids, gabapentin, magnesium or ketamine for situations where neuroaxial anaesthesia cannot be performed, for high-risk patients, or when pain is difficult to control. Peripheral nerve block techniques can also be added, such as transverse abdominis plane block, erector spinae block, or continuous wound infiltration.
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7.
Clinical Management and Therapeutic Strategies for the Thyroid-Associated Ophthalmopathy: Current and Future Perspectives.
Mishra, S, Maurya, VK, Kumar, S, Ankita, , Kaur, A, Saxena, SK
Current eye research. 2020;(11):1325-1341
Abstract
PURPOSE TAO is an organ specific autoimmune disease associated with thyroid, and inflammation of the orbit and periorbital tissues, which is different from systemic autoimmune diseases such as SLE. However, Grave's disease is a kind of systemic autoimmune syndrome which might involve the thyroid, the eye ball and the anterior tibial tissue. Considering the inexplicable understanding of TAO pathogenesis, the disease worsens for the patients. Therefore, this manuscript provides insights into the recent advancements of clinical features, epidemiology, pathogenesis with gene-interactions, diagnosis, including available and novel treatment options for TAO, based on available data including RCTs, meta-analyses, and systematic reviews. METHODS Articles with clinical features, epidemiology, pathogenesis, diagnosis, and treatment of the disease were thoroughly studied. To perform the gene expression and pathway analysis, articles were searched on PubMed, MEDLINE Cochrane Library and ClinicalTrial.gov from 1982 to 2020. To predict novel TAO-specific therapeutic molecule, structure-based drug design (SBDD) was performed. RESULTS We observed gene expression and pathway analysis and SBDD approaches might bring new insights in the field of TAO pathogenesis, diagnosis, and treatment. A genome-wide map of human genetic interactions revealed involvement of crucial cell-signalling pathways, such as TNF-mediated signalling pathway, type-I interferon signalling pathway, toll-like receptor signalling pathway, transforming growth factor-beta receptor signalling pathway etc. Recently, FDA-approved teprotumumab a breakthrough, first drug for the treatment of active thyroid eye disease, which reduces proptosis and the need for orbital decompression surgery. Furthermore, our SBDD results revealed that cost-effective Curcumin, Withaferin A, Resveratrol, Scopolamine, Quercetin, and Berberine may have significant binding affinity for hyaluronan protein and may be exploited for therapeutic purposes in TAO. CONCLUSIONS Considering the increasing risk and nature of disease, novel drug therapies and markers for prognosis need to be investigated. Moreover, evidence-based non-invasive/minimal surgical therapies should be developed for the better management of the disease. ABBREVIATIONS ADIPOQ Adiponectin; CAS: Clinical Activity Score; CCL5: C-C Motif Chemokine Ligand 5; CT: Computed Tomography; DON: Dysthyroid Optic Neuropathy; EUGOGO European Group of Graves' Orbitopathy; FDA: U.S. Food and Drug Administration; FOS: Fos Proto-Oncogene, AP-1 Transcription Factor Subunit; HLA: Human Leukocyte Antigen; HLA-DRA: Major Histocompatibility Complex, Class II, DR Alpha; ICAM1: Intercellular Adhesion Molecule 1; IFNG Interferon Gamma; IGF-1: Insulin-like Growth Factor 1; IGF-1R: Insulin-like Growth Factor-1 Receptor; IL12B: Interleukin 12B; IL23R: Interleukin 23 Receptor; IL6: Interleukin 6; IOP: Intraocular Pressure; IRF1: Interferon Regulatory Factor 1; IRF5: Interferon Regulatory Factor 5; IRF7: Interferon Regulatory Factor 7; IRF9: Interferon Regulatory Factor 9; JUN: Jun Proto-Oncogene, AP-1 Transcription Factor Subunit; JUNB JunB Proto-Oncogene, AP-1 Transcription Factor Subunit; MHC: Major Histocompatibility Complex; MRI: Magnetic Resonance Imaging; NFKB1: Nuclear Factor Kappa B Subunit 1; NFKBIA Nuclear Factor Kappa B Inhibitor Alpha; OADSCs: Orbital Adipose Derived Stromal Cells; PDGFB Platelet Derived Growth Factor Subunit B; PPARG Peroxisome Proliferator Activated Receptor Gamma; RANTES Regulated on Activation Normal T cell Expressed and Secreted; RARA Retinoic Acid Receptor Alpha; RCTs (Randomized Controlled Trials; SLE: Systemic lupus erythematosus; SOCS3: Suppressor of Cytokine Signaling 3; STAT1: Signal Transducer and Activator of Transcription 1; TAO: Thyroid-Associated Ophthalmopathy; TED: Thyroid eye disease; TGFB1: Transforming Growth Factor Beta 1; TGFB2: Transforming Growth Factor Beta 2; TGF-β: Transforming Growth Factor-beta; TLR7: Toll like Receptor 7; TLR9: Toll like Receptor 9; TNFRSF18: Tumor Necrosis Factor Receptor Superfamily Member 18; TNFSF11: Tumor Necrosis Factor Receptor Superfamily Member 11; TNF-α: Tumor Necrosis Factor-alpha; TSHR Thyroid Stimulating Hormone Receptor; TSIs: Thyroid Stimulating Immunoglobulin; WNT5A: Wingless-Type MMTV Integration Site Family, Member 5A.
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8.
Intravenous Migraine Treatment in Children and Adolescents.
Werner, K, Qaiser, S, Kabbouche, M, Murphy, B, Maconochie, I, Hershey, AD
Current pain and headache reports. 2020;(8):45
Abstract
PURPOSE OF REVIEW Pediatric migraine is a common, chronic, and disabling neurological disorder in children and adolescents. Outpatient management is not always effective, and intravenous migraine management may be necessary for headache treatment in the pediatric emergency department. Most current treatment is based on retrospective evidence and there is a lack of well-designed randomized double-blinded controlled pediatric studies. Intravenous drug treatment agents including intravenous fluids, prochlorperazine, diphenhydramine, metoclopramide, dexamethasone, magnesium, valproate and propofol, and dihydroergotamine are reviewed in this paper. RECENT FINDINGS Nineteen studies were reviewed including one prospective randomized double-blind; one single-blinded randomized; one prospective; and one open-label, randomized clinical trial. Most studies were retrospective and the quality of the studies was limited. No definite conclusions can be drawn from the studies, but appropriate prospective trials between major pediatric headache institutions will move pediatric intravenous migraine management forward.
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9.
The Role of Exparel Plus Meloxicam for Postoperative Pain Management.
Kaye, AD, Novitch, MB, Carlson, SF, Fuller, MC, White, SW, Haroldson, AR, Kaiser, JA, Elkersh, MA, Brunk, AJ, Jeha, GM, et al
Current pain and headache reports. 2020;(3):6
Abstract
PURPOSE OF REVIEW Acute postoperative pain reduction is a major target against the opioid crisis. While opioids have traditionally been the mainstay for postoperative analgesia, current practice has focused on a multimodal approach to pain control, including ultrasound-guided blocks with longer acting local anesthetic agents. RECENT FINDINGS Non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, are an important class of medications utilized to manage pain in the perioperative period. An additional treatment used in perioperative or postoperative pain relief is Exparel, a bupivacaine (sodium channel blocker) liposomal injectable suspension with a 3-4-day duration of action. The long-acting mechanism and formulation of Exparel consistently has demonstrated decreased opioid use and pain scores in patients undergoing many different surgical procedures. A concern is that pH negatively alters the efficacy of bupivacaine, as in cases of inflamed tissue and acidic fluid pH. For this reason, a combination medication with both meloxicam and bupivacaine has been developed, which normalizes pH and has anti-inflammatory and anti-pain conduction properties. Clinical studies demonstrate that this combination agent can be extremely beneficial in treating postoperative pain. This manuscript summarizes the newest developments with regard to liposomal bupivacaine and the non-steroidal meloxicam, their roles in effective treatment of postoperative pain, contraindications, special considerations of using these medications, and future considerations. HTX-011 pairs up a new extended-release formulation of the local anesthetic bupivacaine with meloxicam, a well-established non-steroidal anti-inflammatory drug (NSAID).
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10.
Is mesalazine treatment effective in the prevention of diverticulitis? A review.
Stefanelli, G, Viscido, A, Valvano, M, Vernia, F, Frieri, G, Ashktorab, H, Latella, G
European review for medical and pharmacological sciences. 2020;(15):8164-8176
Abstract
Diverticulitis is the most severe form of Diverticular disease (DD). An effective treatment strategy for its prevention has not yet been defined. This review aimed to provide a viewpoint on the role of mesalazine, also note as 5-aminosalicylic acid (5-ASA), in the prevention of diverticulitis. A systematic electronic search of relevant articles was performed using PubMed, Embase, Scopus, and Cochrane. Randomized controlled trials (RCTs), open trials, and retrospective studies, published between January 1999 and January 2020, were identified. Twelve eligible studies that analyzed primary or secondary outcomes of diverticulitis were included. The population included patients with symptomatic uncomplicated diverticular disease (SUDD), or patients with a history of diverticulitis. All studies compared 5-ASA to placebo, rifaximin, or other treatments. Two studies, including 359 patients, assessed the efficacy of 5-ASA in preventing the first appearance of diverticulitis in patients with SUDD. Of these, one showed that 5-ASA was effective, and one did not. Ten studies, including 2.995 patients, assessed the efficacy of 5-ASA treatment in preventing the recurrence of diverticulitis in patients with a history of diverticulitis. Four studies showed that 5-ASA had a certain degree of efficacy. All four RCTs demonstrated that 5-ASA did not significantly reduce the rate of diverticulitis recurrence. In a retrospective trial, 5-ASA was less effective than rifaximin in preventing diverticulitis recurrence. In an open trial, there was no difference between 5-ASA and probiotic treatment. Overall, there is currently conflicting evidence regarding the efficacy of 5-ASA treatment in the prevention of diverticulitis and further RCTs are needed.