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[Conventional analgesics and non-pharmacological multidisciplinary therapeutic treatment in endometriosis: CNGOF-HAS Endometriosis Guidelines].
Wattier, JM
Gynecologie, obstetrique, fertilite & senologie. 2018;(3):248-255
Abstract
UNLABELLED A major symptom of endometriosis is pelvic pain with a wide range of intensity, rhythm, type, and expression, without clearly established relationship between pain and the disease. Endometriosis-associated pain has physical, psychological/behavioral and social consequences with a significant impact on patient quality-of-life in relation with the biopsychosocial model of chronic pain. Pain assessment in all of its dimensions, as well as assessing the consequences of pain is therefore a crucial part of therapeutic management. Conventional analgesics are commonly used although studies demonstrating their efficacy in the treatment of endometriosis-related pelvic pain are lacking. Non-steroid anti-inflammatory drugs (NSAIDs), known to be effective in dysmenorrhea unrelated to endometriosis, have not been recently re-assessed in patients with endometriosis. Following rigorous assessment, the characterization of neuropathic components of endometriosis-related pelvic pain may lead to treatment with antiepileptic of antidepressant drugs, although gabapentin and amitriptyline have yet to be specifically assessed in the setting of endometriosis-related pain. Other pharmacologically active compounds have been tested to treat endometriosis-related pain but did not demonstrate efficacy with sufficient level of evidence. Diets, dietary supplements and herbal medicine are often proposed and/or used as adjuncts without any conclusive evidence. Although the effects on endometriosis-related pain are methodologically difficult to assess, physical adjunctive therapies such as acupuncture, transcutaneous neurostimulation, osteopathy/chiropractics, physical therapy and physical activity, the long-term therapeutic relationship they establish may potentiate beneficial effects perceived by patients. However, it remains difficult to demonstrate significant effects of cognitive and/or behavioral interventions on endometriosis-related pain. CONCLUSION The complexity of managing endometriosis-related pain requires a holistic approach with sustained attention to the patient. Treatments, either pharmacologic or non-pharmacologic, including adjuvant therapies, associate a technical expertise to which a human approach must be added in order to bring value to these treatments. Multidisciplinary and/or inter disciplinary approaches are therefore essential to the care of patients suffering from endometriosis.
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Analgesic Effects of Locally Administered Ketorolac-based Analgesics After Breast Surgery: A Meta-Analysis of Randomized Controlled Trials.
Chen, JY, Feng, IJ, Loh, EW, Wang, LK, Lin, CC, Tam, KW
The Clinical journal of pain. 2018;(6):577-584
Abstract
OBJECTIVE Reducing postoperative pain following breast surgery is crucial for rapid recovery and shortening hospital stay. Ketorolac, a nonsteroidal anti-inflammatory drug, has been used as a postoperative analgesic in many surgical procedures. We conducted a systemic review and meta-analysis on the efficacy of locally administered ketorolac-based analgesics in managing pain after breast surgery. METHODS We searched the PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov registry for randomized control trials (RCTs) published up to September 2016. The primary outcome was pain level assessed using a visual analog scale (VAS) at 1 and 6 hours following breast surgery. RESULTS We reviewed 4 RCTs with 255 patients. For meta-analysis, VAS at 1 and 6 hours of 3 similar RCTs were compared. At 1 hour, VAS scores were significantly lower in patients administered a ketorolac solution [weighted mean difference (WMD)=-2.04; 95% confidence interval (CI): -3.08 to -1.00] or ketorolac-bupivacaine solution (WMD=-2.30; 95% CI, -4.07 to -0.54) than in controls. At 6 hours, the ketorolac-bupivacaine solution reduced VAS scores significantly (WMD=-1.40; 95% CI, -2.48 to -0.32) compared with controls. However, at 1 hour, the ketorolac solution was significantly more effective than the bupivacaine solution was (WMD=-1.70; 95% CI, -2.81 to -0.59). DISCUSSION The effects of ketorolac-based analgesics vary as per the surgery and disease type. Locally administered ketorolac-based analgesics decreased postoperative pain in breast surgery patients, and the effect of local ketorolac was better than local bupivacaine. Therefore, ketorolac-based analgesics demonstrate considerable local infiltration during pain management after breast surgery.
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Rapid-onset hyponatremia and delirium following duloxetine treatment for postherpetic neuralgia: Case report and literature review.
Wang, D, Lai, J, Lu, S, Huang, M, Hu, S, Xu, Y
Medicine. 2018;(46):e13178
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Abstract
RATIONALE Hyponatremia following duloxetine treatment has been reported in patients with major depressive disorder, fibromyalgia, diabetic neuropathy, or sciatic pain. The manifestations of duloxetine-induced hyponatremia are varying in different individuals. The overall prognosis for this type of hyponatremia is favorable if properly managed. PATIENT CONCERNS AND DIAGNOSES Herein, we reported rapid-onset hyponatremia and delirium in an older patient after 2 doses of duloxetine, which was used to control his postherpetic neuralgia. Laboratory examinations revealed a rapid decline in serum sodium level and indicated the possibility of syndrome of inappropriate antidiuretic hormone (SIADH). INTERVENTIONS Discontinuation of duloxetine, restriction of water intake, and intravenous supplement of normal saline were adopted to manage the hyponatremia. OUTCOMES Serum concentration of sodium gradually normalized following aforementioned strategies. LESSONS Special attention to the electrolyte abnormality is recommended in old patients undergoing duloxetine treatment.
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Baseline Morphine Consumption May Explain Between-Study Heterogeneity in Meta-analyses of Adjuvant Analgesics and Improve Precision and Accuracy of Effect Estimates.
Doleman, B, Sutton, AJ, Sherwin, M, Lund, JN, Williams, JP
Anesthesia and analgesia. 2018;(2):648-660
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BACKGROUND Statistical heterogeneity can increase the uncertainty of results and reduce the quality of evidence derived from systematic reviews. At present, it is uncertain what the major factors are that account for heterogeneity in meta-analyses of analgesic adjuncts. Therefore, the aim of this review was to identify whether various covariates could explain statistical heterogeneity and use this to improve accuracy when reporting the efficacy of analgesics. METHODS We searched for reviews using MEDLINE, EMBASE, CINAHL, AMED, and the Cochrane Database of Systematic Reviews. First, we identified the existence of considerable statistical heterogeneity (I > 75%). Second, we conducted meta-regression analysis for the outcome of 24-hour morphine consumption using baseline risk (control group morphine consumption) and other clinical and methodological covariates. Finally, we constructed a league table of adjuvant analgesics using a novel method of reporting effect estimates assuming a fixed consumption of 50 mg postoperative morphine. RESULTS We included 344 randomized controlled trials with 28,130 participants. Ninety-one percent of analyses showed considerable statistical heterogeneity. Baseline risk was a significant cause of between-study heterogeneity for acetaminophen, nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, tramadol, ketamine, α2-agonists, gabapentin, pregabalin, lidocaine, magnesium, and dexamethasone (R = 21%-100%; P < .05). There was some evidence that the methodological limitations of the trials explained some of the residual heterogeneity. Type of surgery was not independently associated with analgesic efficacy. Assuming a fixed baseline risk of 50 mg (in order of efficacy), gabapentin, acetaminophen, α2-agonists, nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, pregabalin, tramadol, magnesium, and lidocaine demonstrated moderate clinically significant reductions (>10 mg). We could not exclude a moderate clinically significant effect with ketamine. Dexamethasone demonstrated a small clinical benefit (>5 mg). CONCLUSIONS We empirically identified baseline morphine consumption as the major source of heterogeneity in meta-analyses of adjuvant analgesics across all surgical interventions. Controlling for baseline morphine consumption, clinicians can use audit data to estimate the morphine-reducing effect of adding any adjuvant for their local population, regardless which surgery they undergo. Moreover, we have utilized these findings to present a novel method of reporting and an amended method of graphically displaying effect estimates, which both reduces confounding from variable baseline risk in included trials and is able to adjust for other clinical and methodological confounding variables. We recommend use of these methods in clinical practice and future reviews of analgesics for postoperative pain.
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Treatment of drug-resistant fibromyalgia symptoms using high-intensity laser therapy: a case-based review.
White, PF, Zafereo, J, Elvir-Lazo, OL, Hernandez, H
Rheumatology international. 2018;(3):517-523
Abstract
Fibromyalgia is a chronic musculoskeletal condition characterized by widespread pain in the body and is associated with tender points at the shoulder, back and hip regions. A wide variety of pharmacologic drugs and dietary supplements have been used with limited success in treating the musculoskeletal pain. Early clinical studies with low level laser therapy (LLLT) alone or in combination with drugs commonly used to treat fibromyalgia suggested that LLLT may be effective in reducing musculoskeletal pain and stiffness, as well as the number of tender locations. However, a sham-controlled study reported that LLLT was not significantly better than the sham treatment and kinesiotape. Preliminary studies with high-intensity laser therapy (HILT) suggest that it may be more effective than LLLT for treating chronic pain syndromes. Therefore, we evaluated low (1 W), intermediate (42 W) and high level (75 W) HILT in a woman with long-standing fibromyalgia syndrome which was resistant to both standard pharmacotherapy and treatment in an interdisciplinary pain management program. The patient received a series of treatments with a HILT device (Phoenix Thera-lase) at a wavelength of 1275 nm administered at both the paraspinous region and tender points in the shoulder and hip regions. Although the 1 W treatment produced minimal symptom relief, both the 42 and the 75 W treatments produced a dramatic reduction in her overall pain, improved quality of sleep, and increased her level of physical activity for 4-10 days after these treatment sessions. This case illustrates the potential beneficial effects of using higher power levels of HILT for patients with fibromyalgia syndrome who have failed to respond to conventional interdisciplinary treatment regimens.
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Emerging therapies for neuropathic pain: new molecules or new indications for old treatments?
Bouhassira, D, Attal, N
Pain. 2018;(3):576-582
Abstract
Neuropathic pain represents a highly unmet medical need because most of the available treatments have a modest efficacy or dose-limiting side effects. Hence, novel therapeutic perspectives are warranted. Many compounds acting on new pain targets are in preclinical or early clinical development. Only few clinical trials have suggested their clinical relevance in neuropathic pain. This concerns in particular NaV1.7 antagonists and angiotensin type II inhibitors. Another type of emerging drug therapy in neuropathic pain is represented by drugs largely used for other indications, such as botulinum toxin A and the antiepileptic oxcarbazepine, which have recently found to be effective in peripheral neuropathic pain. Emerging nondrug medical therapy with promising results in neuropathic pain also encompasses noninvasive brain neurostimulation techniques, such as repetitive transcranial magnetic stimulation and transcranial direct electrical stimulation. In this article, we review emerging medical treatments for neuropathic pain that are clinically available or with promising results from clinical trials.
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Analgesic efficacy of preoperative dexketoprofen trometamol: A systematic review and meta-analysis.
Esparza-Villalpando, V, Pozos-Guillén, A, Masuoka-Ito, D, Gaitán-Fonseca, C, Chavarría-Bolaños, D
Drug development research. 2018;(2):47-57
Abstract
Post-Market Research Clinical evidence supports the use of dexketoprofen trometamol (DEX) to manage acute postoperative pain. However, controversies surround the impact of the use of this drug in preoperative analgesic protocols. The aim of the present meta-analysis was to evaluate the effectiveness of the preoperative administration of DEX under postoperative pain conditions. Electronic and manual searches were conducted through diverse electronic databases. A systematic review and meta-analysis to evaluate the analgesic efficacy of the preoperative administration of DEX was performed including Randomized Clinical Trials (RCTs) published between 2002 and 2017. Suitable individual studies were evaluated through a quality system, and the data were extracted and analyzed. Fourteen RTCs were included (12 parallel trials and 2 cross-over trials), published in the English and Turkish languages. Follow-up periods ranged from 4, 6, 8, 24, and 48 hr. All trials measured the outcome result as Acute Pain Level (APL) (VAS, NRS, VRS), time to requiring a second dose of DEX or analgesic emergency and consumption of opioids via patient-controlled analgesia. When the comparators were other drugs - paracetamol, Lornoxicam or placebo during the preoperative time, preoperative administration of DEX was superior. When the comparison comprised preoperative and postoperative DEX, both alternatives exhibited comparable analgesic effects. The analgesic efficacy of the preoperative administration of DEX when compared to placebo, lornoxicam, and paracetamol on postoperative pain was evident. Preoperative administration of DEX compared to its immediate postoperative administration showed a similar analgesic effect.
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Headache and pregnancy: a systematic review.
Negro, A, Delaruelle, Z, Ivanova, TA, Khan, S, Ornello, R, Raffaelli, B, Terrin, A, Reuter, U, Mitsikostas, DD, ,
The journal of headache and pain. 2017;(1):106
Abstract
This systematic review summarizes the existing data on headache and pregnancy with a scope on clinical headache phenotypes, treatment of headaches in pregnancy and effects of headache medications on the child during pregnancy and breastfeeding, headache related complications, and diagnostics of headache in pregnancy. Headache during pregnancy can be both primary and secondary, and in the last case can be a symptom of a life-threatening condition. The most common secondary headaches are stroke, cerebral venous thrombosis, subarachnoid hemorrhage, pituitary tumor, choriocarcinoma, eclampsia, preeclampsia, idiopathic intracranial hypertension, and reversible cerebral vasoconstriction syndrome. Migraine is a risk factor for pregnancy complications, particularly vascular events. Data regarding other primary headache conditions are still scarce. Early diagnostics of the disease manifested by headache is important for mother and fetus life. It is especially important to identify "red flag symptoms" suggesting that headache is a symptom of a serious disease. In order to exclude a secondary headache additional studies can be necessary: electroencephalography, ultrasound of the vessels of the head and neck, brain MRI and MR angiography with contrast ophthalmoscopy and lumbar puncture. During pregnancy and breastfeeding the preferred therapeutic strategy for the treatment of primary headaches should always be a non-pharmacological one. Treatment should not be postponed as an undermanaged headache can lead to stress, sleep deprivation, depression and poor nutritional intake that in turn can have negative consequences for both mother and baby. Therefore, if non-pharmacological interventions seem inadequate, a well-considered choice should be made concerning the use of medication, taking into account all the benefits and possible risks.
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Effect of preoperative oral analgesics on pulpal anesthesia in patients with irreversible pulpitis-a systematic review and meta-analysis.
Shirvani, A, Shamszadeh, S, Eghbal, MJ, Marvasti, LA, Asgary, S
Clinical oral investigations. 2017;(1):43-52
Abstract
OBJECTIVES The objectives of this study were to assess the efficacy of preemptive oral administration of single dose of non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the local anesthetic success in adults with irreversible pulpitis and to find the possible covariates that could predict treatment effect. MATERIALS AND METHODS A systematic search using electronic databases up to March 2015 was conducted. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated using random and fixed-effect inverse variance method. Subgroup and meta-regression analyses were conducted to assess the potential source of heterogeneity. RESULTS Results showed that preemptive analgesics are more effective than placebo in increasing anesthetic success (OR = 0.30, CI% 0.24-0.39, p = 0.000) [Q = 55.860 (p = 0.001)]. In the subgroup analysis, administration of NSAIDs as monotherapy, ibuprofen as mono- vs. combination therapy, oxicam type drugs as monotherapy, and acetaminophen as combination therapy were significantly more effective in increasing anesthetic success OR = 0.25, CI% 0.16-0.38, p = 0.00, Q = 40.539 (p = 0.003); OR = 0.44, CI% 0.26-0.75, p = 0.00, Q = 12.833 (p = 0.011); OR = 0.48, CI% 0.30-0.74, p = 0.002, Q = 15.898 (p = 0.14); OR = 0.30, CI% 0.16-0.38, p = 0.001, Q = 7.506 (p = 0.02); OR = 0.10, CI% 0.16 0.38, p = 0.001, Q = 5.075 (p = 0.07), respectively. However, there was no significant difference in increasing anesthetic success between treatment and placebo arms when acetaminophen was administrated alone. In meta-regression analysis, an association between different types of NSAIDs (indomethacin, diclofenac potassium, and oxicam-type drugs) and articaine with treatment effect was observed. CONCLUSIONS The administration of preemptive analgesics can induce superior intraoperative analgesia for patients with irreversible pulpitis. However, strategies such as co-administration of certain types of analgesics and anesthetic solution might be predictors of treatment effect. Additionally, there was no association between different timing and dosage of analgesics and treatment effect. CLINICAL RELEVANCE When compared to placebo, preemptive oral analgesics are superior in achieving anesthetic success in inflamed pulp.
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Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews.
Derry, S, Wiffen, PJ, Kalso, EA, Bell, RF, Aldington, D, Phillips, T, Gaskell, H, Moore, RA
The Cochrane database of systematic reviews. 2017;(5):CD008609
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BACKGROUND Topical analgesic drugs are used for a variety of painful conditions. Some are acute, typically strains or sprains, tendinopathy, or muscle aches. Others are chronic, typically osteoarthritis of hand or knee, or neuropathic pain. OBJECTIVES To provide an overview of the analgesic efficacy and associated adverse events of topical analgesics (primarily nonsteroidal anti-inflammatory drugs (NSAIDs), salicylate rubefacients, capsaicin, and lidocaine) applied to intact skin for the treatment of acute and chronic pain in adults. METHODS We identified systematic reviews in acute and chronic pain published to February 2017 in the Cochrane Database of Systematic Reviews (the Cochrane Library). The primary outcome was at least 50% pain relief (participant-reported) at an appropriate duration. We extracted the number needed to treat for one additional beneficial outcome (NNT) for efficacy outcomes for each topical analgesic or formulation, and the number needed to treat for one additional harmful outcome (NNH) for adverse events. We also extracted information on withdrawals due to lack of efficacy or adverse events, systemic and local adverse events, and serious adverse events. We required information from at least 200 participants, in at least two studies. We judged that there was potential for publication bias if the addition of four studies of typical size (400 participants) with zero effect increased NNT compared with placebo to 10 (minimal clinical utility). We extracted GRADE assessment in the original papers, and made our own GRADE assessment. MAIN RESULTS Thirteen Cochrane Reviews (206 studies with around 30,700 participants) assessed the efficacy and harms from a range of topical analgesics applied to intact skin in a number of acute and chronic painful conditions. Reviews were overseen by several Review Groups, and concentrated on evidence comparing topical analgesic with topical placebo; comparisons of topical and oral analgesics were rare.For at least 50% pain relief, we considered evidence was moderate or high quality for several therapies, based on the underlying quality of studies and susceptibility to publication bias.In acute musculoskeletal pain (strains and sprains) with assessment at about seven days, therapies were diclofenac Emulgel (78% Emulgel, 20% placebo; 2 studies, 314 participants, NNT 1.8 (95% confidence interval 1.5 to 2.1)), ketoprofen gel (72% ketoprofen, 33% placebo, 5 studies, 348 participants, NNT 2.5 (2.0 to 3.4)), piroxicam gel (70% piroxicam, 47% placebo, 3 studies, 522 participants, NNT 4.4 (3.2 to 6.9)), diclofenac Flector plaster (63% Flector, 41% placebo, 4 studies, 1030 participants, NNT 4.7 (3.7 to 6.5)), and diclofenac other plaster (88% diclofenac plaster, 57% placebo, 3 studies, 474 participants, NNT 3.2 (2.6 to 4.2)).In chronic musculoskeletal pain (mainly hand and knee osteoarthritis) therapies were topical diclofenac preparations for less than six weeks (43% diclofenac, 23% placebo, 5 studies, 732 participants, NNT 5.0 (3.7 to 7.4)), ketoprofen over 6 to 12 weeks (63% ketoprofen, 48% placebo, 4 studies, 2573 participants, NNT 6.9 (5.4 to 9.3)), and topical diclofenac preparations over 6 to 12 weeks (60% diclofenac, 50% placebo, 4 studies, 2343 participants, NNT 9.8 (7.1 to 16)). In postherpetic neuralgia, topical high-concentration capsaicin had moderate-quality evidence of limited efficacy (33% capsaicin, 24% placebo, 2 studies, 571 participants, NNT 11 (6.1 to 62)).We judged evidence of efficacy for other therapies as low or very low quality. Limited evidence of efficacy, potentially subject to publication bias, existed for topical preparations of ibuprofen gels and creams, unspecified diclofenac formulations and diclofenac gel other than Emulgel, indomethacin, and ketoprofen plaster in acute pain conditions, and for salicylate rubefacients for chronic pain conditions. Evidence for other interventions (other topical NSAIDs, topical salicylate in acute pain conditions, low concentration capsaicin, lidocaine, clonidine for neuropathic pain, and herbal remedies for any condition) was very low quality and typically limited to single studies or comparisons with sparse data.We assessed the evidence on withdrawals as moderate or very low quality, because of small numbers of events. In chronic pain conditions lack of efficacy withdrawals were lower with topical diclofenac (6%) than placebo (9%) (11 studies, 3455 participants, number needed to treat to prevent (NNTp) 26, moderate-quality evidence), and topical salicylate (2% vs 7% for placebo) (5 studies, 501 participants, NNTp 21, very low-quality evidence). Adverse event withdrawals were higher with topical capsaicin low-concentration (15%) than placebo (3%) (4 studies, 477 participants, NNH 8, very low-quality evidence), topical salicylate (5% vs 1% for placebo) (7 studies, 735 participants, NNH 26, very low-quality evidence), and topical diclofenac (5% vs 4% for placebo) (12 studies, 3552 participants, NNH 51, very low-quality evidence).In acute pain, systemic or local adverse event rates with topical NSAIDs (4.3%) were no greater than with topical placebo (4.6%) (42 studies, 6740 participants, high quality evidence). In chronic pain local adverse events with topical capsaicin low concentration (63%) were higher than topical placebo (5 studies, 557 participants, number needed to treat for harm (NNH) 2.6), high quality evidence. Moderate-quality evidence indicated more local adverse events than placebo in chronic pain conditions with topical diclofenac (NNH 16) and local pain with topical capsaicin high-concentration (NNH 16). There was moderate-quality evidence of no additional local adverse events with topical ketoprofen over topical placebo in chronic pain. Serious adverse events were rare (very low-quality evidence).GRADE assessments of moderate or low quality in some of the reviews were considered by us to be very low because of small numbers of participants and events. AUTHORS' CONCLUSIONS There is good evidence that some formulations of topical diclofenac and ketoprofen are useful in acute pain conditions such as sprains or strains, with low (good) NNT values. There is a strong message that the exact formulation used is critically important in acute conditions, and that might also apply to other pain conditions. In chronic musculoskeletal conditions with assessments over 6 to 12 weeks, topical diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis, as did topical high-concentration capsaicin in postherpetic neuralgia. Though NNTs were higher, this still indicates that a small proportion of people had good pain relief.Use of GRADE in Cochrane Reviews with small numbers of participants and events requires attention.