Explore the vast range of titles available.

Background: The 7-day, low-dose buprenorphine patch has been available in the United Kingdom since 2005 for the treatment of chronic nonmalignant pain that is unresponsive to nonopioid analgesics. Osteo-arthritis pain, a significant cause of pain and disability in the elderly, is a common reason for prescribing bu-prenorphine patches. Objectives: The goals of this study were to investigate utilization and treatment persistence in patients receiving low-dose buprenorphine patches and the expected patterns of treatment 12 months after the initiation of treatment. Methods: This was a retrospective cohort study of patients who were prescribed low-dose buprenorphine patches in general practice in the United Kingdom. Patients in this cohort were matched by age, sex, and practice with comparator cohorts prescribed oral codeine, dihydrocodeine, or tramadol. Data on baseline characteristics, utilization, and adverse events were obtained from the General Practice Research Database, which contains computerized medical records from UK general practice. Treatment persistence was determined based on repeat prescribing within 90 days after the expected end of a prescription; rates of persistence were compared between the buprenorphine and comparator cohorts. Cox proportional hazards regression models were used to compare the incidence of typical opioid adverse effects (constipation, dizziness, and nausea and/or vomiting) between cohorts. Results: The study cohort included 4968 patients who were prescribed low-dose buprenorphine patches. The majority of patients (64.2%) were aged >65 years, and the most frequently recorded indication for low-dose buprenorphine patches was osteoarthritis (48.7%). Most patients (76.1%) started treatment at the lowest patch strength (5 μ/h). The mean patch strength prescribed over time stabilized at 10 to 12 μ/h. Persistence with low-dose buprenorphine patches over 6 months was significantly higher than with codeine, dihydrocodeine, and tramadol (28.9%, 22.4%, 24.4%, and 23.8%, respectively; P < 0.01). Persistence over 12 months also was significantly higher with low-dose buprenorphine patches compared with the comparators (18.5%, 16.1%, 18.0%, and 17.6%; P < 0.01). After 12 months, the difference in persistence levels between cohorts was not statistically significant. In the Cox proportional hazards regression models, patients using buprenorphine patches had an increased incidence of constipation, dizziness, and nausea and vomiting compared with those who used the comparator opioids ( P < 0.05). Conclusions: Significantly more patients receiving low-dose buprenorphine patches in this study persisted with treatment at 6 and 12 months compared with those receiving other opioid analgesics. Treatment with low-dose buprenorphine patches was most frequently initiated at the lowest patch strength and stabilized at a mean of 10 to 12 μ/h.

Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7–10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain. Neuropathic pain is caused by a lesion or disease of the somatosensory system (including peripheral and central neurons). Here, the authors present the current descriptions of the presentation, causes, diagnosis and treatment of neuropathic pain with a focus on peripheral neuropathic pain, which has a greater knowledge base than central neuropathic pain.

We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.

AbstractObjectiveTo determine the risk of prolonged opioid use in patients receiving tramadol compared with other short acting opioids.DesignObservational study of administrative claims data.SettingUnited States commercial and Medicare Advantage insurance claims (OptumLabs Data Warehouse) January 1, 2009 through June 30, 2018.ParticipantsOpioid-naive patients undergoing elective surgery.Main outcome measureRisk of persistent opioid use after discharge for patients treated with tramadol alone compared with other short acting opioids, using three commonly used definitions of prolonged opioid use from the literature: additional opioid use (defined as at least one opioid fill 90-180 days after surgery); persistent opioid use (any span of opioid use starting in the 180 days after surgery and lasting ≥90 days); and CONSORT definition (an opioid use episode starting in the 180 days after surgery that spans ≥90 days and includes either ≥10 opioid fills or ≥120 days’ supply of opioids).ResultsOf 444 764 patients who met the inclusion criteria, 357 884 filled a discharge prescription for one or more opioids associated with one of 20 included operations. The most commonly prescribed post-surgery opioid was hydrocodone (53.0% of those filling a single opioid), followed by short acting oxycodone (37.5%) and tramadol (4.0%). The unadjusted risk of prolonged opioid use after surgery was 7.1% (n=31 431) with additional opioid use, 1.0% (n=4457) with persistent opioid use, and 0.5% (n=2027) meeting the CONSORT definition. Receipt of tramadol alone was associated with a 6% increase in the risk of additional opioid use relative to people receiving other short acting opioids (incidence rate ratio 95% confidence interval 1.00 to 1.13; risk difference 0.5 percentage points; P=0.049), 47% increase in the adjusted risk of persistent opioid use (1.25 to 1.69; 0.5 percentage points; P<0.001), and 41% increase in the adjusted risk of a CONSORT chronic opioid use episode (1.08 to 1.75; 0.2 percentage points; P=0.013).ConclusionsPeople receiving tramadol alone after surgery had similar to somewhat higher risks of prolonged opioid use compared with those receiving other short acting opioids. Federal governing bodies should consider reclassifying tramadol, and providers should use as much caution when prescribing tramadol in the setting of acute pain as for other short acting opioids.

AbstractObjectiveTo evaluate the comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain.DesignSystematic review and network meta-analysis.Data sourcesMedline, PubMed, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and World Health Organization’s International Clinical Trials Registry Platform from database inception to 20 February 2022.Eligibility criteria for study selectionRandomised controlled trials of analgesic medicines (eg, non-steroidal anti-inflammatory drugs, paracetamol, opioids, anti-convulsant drugs, skeletal muscle relaxants, or corticosteroids) compared with another analgesic medicine, placebo, or no treatment. Adults (≥18 years) who reported acute non-specific low back pain (for less than six weeks).Data extraction and synthesisPrimary outcomes were low back pain intensity (0-100 scale) at end of treatment and safety (number of participants who reported any adverse event during treatment). Secondary outcomes were low back specific function, serious adverse events, and discontinuation from treatment. Two reviewers independently identified studies, extracted data, and assessed risk of bias. A random effects network meta-analysis was done and confidence was evaluated by the Confidence in Network Meta-Analysis method.Results98 randomised controlled trials (15 134 participants, 49% women) included 69 different medicines or combinations. Low or very low confidence was noted in evidence for reduced pain intensity after treatment with tolperisone (mean difference −26.1 (95% confidence intervals −34.0 to −18.2)), aceclofenac plus tizanidine (−26.1 (−38.5 to −13.6)), pregabalin (−24.7 (−34.6 to −14.7)), and 14 other medicines compared with placebo. Low or very low confidence was noted for no difference between the effects of several of these medicines. Increased adverse events had moderate to very low confidence with tramadol (risk ratio 2.6 (95% confidence interval 1.5 to 4.5)), paracetamol plus sustained release tramadol (2.4 (1.5 to 3.8)), baclofen (2.3 (1.5 to 3.4)), and paracetamol plus tramadol (2.1 (1.3 to 3.4)) compared with placebo. These medicines could increase the risk of adverse events compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes.ConclusionsThe comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain are uncertain. Until higher quality randomised controlled trials of head-to-head comparisons are published, clinicians and patients are recommended to take a cautious approach to manage acute non-specific low back pain with analgesic medicines.Systematic review registrationPROSPERO CRD42019145257

Post-operative pain is among the major post-cesarean problems, with an incidence ranging from 25.5% to 80%. Despite its simplicity, the effectiveness of wound infiltration with a mixture of bupivacaine and tramadol is still unknown. Therefore, this study aims to compare the analgesic effectiveness of wound infiltration with bupivacaine versus a combination of bupivacaine and tramadol for postoperative pain management among parturients undergoing cesarean section under spinal anesthesia. A double-blind, parallel, randomized controlled trial was conducted on 60 parturients. Parturients were randomized to take either bupivacaine (B = 30) or a combination of bupivacaine and tramadol (BT = 30). The homogeneity of variance was assessed using Levene's test, and normality was assessed using the Shapiro-Wilk test. A numeric rating scale was used to measure pain severity. The independent t-test and the Mann-Whitney U test were used, respectively, for parametric and non-parametric data. A generalized estimating equation was used to assess repeated measurements. In total, 60 parturients were analyzed with no dropouts. The severity of pain at the 6th hour was six times greater in the B group compared to the BT group (OR = 6.289, CI, 2.097-18.858, P = 0.001). The mean tramadol consumption was lower in the BT group (140.00 ± 48.066 mg) than in the B group (175.00 ± 34.114 mg), with a statistically significant mean difference of 10.761 (95% CI, 13.459 to 56.541), t (58) = 3.252, P = 0.002, (d = 0.839). The mean first analgesia request time was higher in the mixture of the BT group (367.33 ± 50.099 min) than in the B group (216.33 ± 68.744 min), with a statistically significant difference of 15.530 (95% CI, -182.087 to -119.913), t (58) = 5.6553, P = 0.001. Wound infiltration with a combination of bupivacaine and tramadol is more effective than bupivacaine alone for postoperative analgesia in pregnant patients who underwent cesarean section under spinal anesthesia. This clinical trial study was registered at the Pan African Clinical Trial Registry with a unique trial registration number of PACTR202310525672884 (13/10/2023).

Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-L-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.

HSK21542, a peripherally restricted kappa opioid receptor agonist, was evaluated for efficacy and safety in patients with postoperative pain following abdominal surgery. This was assessed in two phase 3, multicentre, randomized, double-blind, controlled trials (HSK21542-301 [ClinicalTrials.gov identifier, NCT04738357] and HSK21542-303 [ClinicalTrials.gov identifier, NCT05390905]) in China. HSK21542-301 was a dual-arm study comparing HSK21542 1.0 μg/kg with placebo, while HSK21542-303 involved three arms comparing HSK21542 1.0 μg/kg with tramadol 50 mg/dose and placebo. All treatments were administered intravenously. The primary endpoint was the time-weighted summed pain intensity differences over 24 h (SPID 0-24 h ). Both HSK21542-301 (least squares [LS] mean [± standard error], −39.1 [1.88] vs −27.4 [1.89]; P  < 0.001) and HSK21542-303 (−64.0 [2.25] vs −45.9 [2.25]; P  < 0.001) demonstrated superiority of HSK21542 over placebo in terms of SPID 0-24 h , while HSK21542-303 showed non-inferiority to tramadol (LS mean difference, −1.1; 95% confidence interval, −7.4 to 5.1; P  < 0.001). Furthermore, HSK21542 had a comparable safety profile to placebo, inducing fewer gastrointestinal adverse events compared with tramadol. Grade ≥3 treatment-emergent adverse events occurred in eight (5.9%) and three (2.3%) patients in the HSK21542 arm of HSK21542-301 and HSK21542-303, respectively. In conclusion, HSK21542 showed potent analgesic effect and was well tolerated in patients who underwent abdominal surgery and experienced postoperative pain. Commonly used opioids for pain management primarily target the mu opioid receptor. However, mu opioid receptor agonists often come with harmful side effects. Here, the authors report the results of two phase 3 trials of HSK21542 (anrikefon), a highly selective activator of peripheral kappa opioid receptor agonists, for postoperative pain treatment following abdominal surgery.

The current Dutch Pharmacogenetics Working Group (DPWG) guideline, describes the gene–drug interaction between CYP2D6 and the opioids codeine, tramadol and oxycodone. CYP2D6 genotype is translated into normal metaboliser (NM), intermediate metaboliser (IM), poor metaboliser (PM) or ultra-rapid metaboliser (UM). Codeine is contraindicated in UM adults if doses >20 mg every 6 h (q6h), in children ≥12 years if doses >10 mg q6h, or with additional risk factors. In PMs, an alternative analgesic should be given which is not or to a lesser extent metabolised by CYP2D6 (not tramadol). In IMs with insufficient analgesia, a higher dose or alternative analgesic should be given. For tramadol, the recommendations for IMs and PMs are the same as the recommendation for codeine and IMs. UMs should receive an alternative drug not or to a lesser extent metabolised by CYP2D6 or the dose should be decreased to 40% of the commonly prescribed dose. Due to the absence of effect on clinical outcomes of oxycodone in PMs, IMs and UMs no action is required. DPWG classifies CYP2D6 genotyping for codeine “beneficial” and recommends testing prior to, or shortly after initiation of treatment in case of higher doses or additional risk factors. CYP2D6 genotyping is classified as “potentially beneficial” for tramadol and can be considered on an individual patient basis.

Longitudinal data on perioperative opioid use for pediatric orthopedic fractures are sparse. This study evaluated 15-year trends in perioperative opioid use for pediatric distal humerus fractures in Korea. Population-based medical data from 51,638,809 subscribers to the Health Insurance Review and Assessment Service were analyzed to assess perioperative opioid use patterns. We reviewed patients aged 2–12 years who underwent closed reduction and percutaneous pinning between 2007 and 2021. A total of 33,770 cases were identified, including 17,945 cases of perioperative opioid use. Injectable opioids were administered in 17,665 cases, and oral opioids were administered in 642 cases. The two most commonly used opioids were injectable fentanyl (60.7%) and injectable tramadol (36.8%). The percentage of total opioid use increased from 40.7% in 2007 to 63.5% in 2018. While the use of injectable fentanyl has steadily increased, the use of injectable tramadol has decreased since 2017. More than half of the pediatric patients who underwent surgery for distal humerus fractures received opioids during the perioperative period. Most commonly used opioid was injectable fentanyl, and its usage continued to increase, representing almost all opioids used in surgeries by 2021. Further research is necessary to analyze the effect of this trend change in injectable fentanyl and tramadol use, offering with recommendations for reducing opioids.