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The design and methods of genetic studies on acute and chronic postoperative pain in patients after total knee replacement.

ABSTRACT: OBJECTIVE:Total knee replacement (TKR) is the treatment option of choice for the millions of individuals whose osteoarthritis pain can no longer be managed through non-invasive methods. Over 500,000 TKRs are performed annually in the United States. Although most patients report improvement in pain and functioning following TKR, up to 30% report persistent pain that interferes with daily function. However, the reasons for poor outcomes are not clear. To best determine which patients are at risk for pain post TKR, a detailed and comprehensive approach is needed. In this article, we present the methodology of a study designed to identify a set of genetic, proteomic, clinical, demographic, psychosocial, and psychophysical risk factors for severe acute and chronic pain post TKR. DESIGN:Prospective longitudinal observational study. SETTING:University Hospital System. SUBJECTS:Patients scheduled for unilateral TKR with a target number of 150. METHODS:Prior to surgery, we collect demographic, psychosocial, and pain data. Biological data, including blood samples for genetic analyses, and serum, urine, and joint fluid for cytokine assessment are collected intraoperatively. Pain assessments as well as medication use are collected during each of the three days postsurgery. Additionally, pain and psychosocial information is collected 6 and 12 months following surgery. CONCLUSIONS:This study, for the first time, captures the information on both genetic and "environmental" risk factors for acute and chronic pain post-TKR and has the potential to lead to the next step-multicenter large-scale studies on predictors and biomarkers of poor TKR outcomes as well as on tailored interventions and personalized medicine approaches for those at risk.

SUBMITTER: Belfer I

PROVIDER: S-EPMC4556363 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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The design and methods of genetic studies on acute and chronic postoperative pain in patients after total knee replacement.

Belfer Inna I Greco Carol M CM Lokshin Anna A Vulakovich Katie K Landsittel Douglas D Dai Feng F Crossett Lawrence L Chelly Jacques E JE

Pain medicine (Malden, Mass.) 20140708 9

<h4>Objective</h4>Total knee replacement (TKR) is the treatment option of choice for the millions of individuals whose osteoarthritis pain can no longer be managed through non-invasive methods. Over 500,000 TKRs are performed annually in the United States. Although most patients report improvement in pain and functioning following TKR, up to 30% report persistent pain that interferes with daily function. However, the reasons for poor outcomes are not clear. To best determine which patients are a ...[more]

PMID: 25040948

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Project description:Pain is the main impetus for osteoarthritis (OA) patients to seek healthcare including joint replacement. The pain experience in OA is heterogeneous and affected by factors across multiple domains-peripheral, psychological, and neurological. This indicates the existence of homogenous subgroups/phenotypes within OA patients with pain. We recently identified three pain phenotypes using a wide spectrum of pain-related factors, including structural damage on magnetic resonance imaging (MRI), emotional problems, number of painful sites, sex, body mass index, education level and comorbidities (i.e., Class 1: high prevalence of emotional problems and low prevalence of structural damage (25%); Class 2: low prevalence of emotional problems and high prevalence of structural damage (20%); Class 3: low prevalence of emotional problems and low prevalence of structural damage (55%)). This study was to examine whether the total knee replacement (TKR) risk over 12 years was different among these three pain phenotypes. Data on 963 participants (mean age 62.8 ± 7.4 years) from a population-based cohort study were utilised. Data on socio-demographic, psychological and comorbidities were collected. MRI of the right knee structural pathology was performed. TKR history was ascertained by linking to the Australian Orthopedic Association National Joint Replacement Registry. Latent class analysis and the Cox proportional hazards model were applied for the analysis. During the follow-up period, 41 right and 44 left TKRs in 67 participants were identified. In multivariable analyses, participants in Class 1 and 2 had a higher risk of having a TKR (Class 1 vs. Class 3, HR (hazard ratio) 4.81, 95%CI (confidence interval) 2.33-9.93; Class 2 vs. Class 3, HR 9.23, 95%CI 4.66-18.30). These associations were stronger in the imaged right knee but were also significant in the left knee. Participants within distinct pain phenotypes have different risks of TKR, suggesting that the identified phenotypes reflect distinct clinical subgroups with different prognoses. The risk for TKR was higher in Class 1 than that in Class 3, suggesting that pain/emotional status is a stronger driver for TKR than structural damage, and that selecting patients for TKR needs to be optimized in clinical practice.

Project description:ObjectiveTo identify postoperative patient-related risk factors for chronic pain after total knee replacement (TKR).DesignThe systematic review protocol was registered on the International Prospective Register of Systematic Reviews (CRD42016041374). MEDLINE, Embase and PsycINFO were searched from inception to October 2016 with no language restrictions. Key articles were also tracked in the Institute for Scientific Information (ISI) Web of Science. Cohort studies evaluating the association between patient-related factors in the first 3?months postoperatively and pain at 6?months or longer after primary TKR surgery were included. Screening, data extraction and assessment of methodological quality were undertaken by two reviewers. The primary outcome was pain severity in the replaced knee measured with a patient-reported outcome measure at 6?months or longer after TKR. Secondary outcomes included adverse events and other aspects of pain recommended by the core outcome set for chronic pain after TKR.ResultsAfter removal of duplicates, 16?430 articles were screened, of which 805 were considered potentially relevant. After detailed evaluation of full-text articles, 14 studies with data from 1168 participants were included. Postoperative patient-related factors included acute pain (eight studies), function (five studies) and psychosocial factors (four studies). The included studies had diverse methods for assessment of potential risk factors and outcomes, and therefore narrative synthesis was conducted. For all postoperative factors, there was insufficient evidence to draw firm conclusions about the association with chronic pain after TKR. Selection bias was a potential risk for all studies, as none were reported to be conducted at multiple centres.ConclusionThis systematic review found insufficient evidence to draw firm conclusions about the association between any postoperative patient-related factors and chronic pain after TKR. Further high-quality research is required to provide a robust evidence base on postoperative risk factors, and inform the development and evaluation of targeted interventions to optimise patients' outcomes after TKR.

Project description:OBJECTIVES:For many people with advanced osteoarthritis, total knee replacement (TKR) is an effective treatment for relieving pain and improving function. Features of perioperative care may be associated with the adverse event of chronic pain 6 months or longer after surgery; effects may be direct, for example, through nerve damage or surgical complications, or indirect through adverse events. This systematic review aims to evaluate whether non-surgical perioperative interventions prevent long-term pain after TKR. METHODS:We conducted a systematic review of perioperative interventions for adults with osteoarthritis receiving primary TKR evaluated in a randomised controlled trial (RCT). We searched The Cochrane Library, MEDLINE, Embase, PsycINFO and CINAHL until February 2018. After screening, two reviewers evaluated articles. Studies at low risk of bias according to the Cochrane tool were included. INTERVENTIONS:Perioperative non-surgical interventions; control receiving no intervention or alternative treatment. PRIMARY AND SECONDARY OUTCOME MEASURES:Pain or score with pain component assessed at 6 months or longer postoperative. RESULTS:44 RCTs at low risk of bias assessed long-term pain. Intervention heterogeneity precluded meta-analysis and definitive statements on effectiveness. Good-quality research provided generally weak evidence for small reductions in long-term pain with local infiltration analgesia (three studies), ketamine infusion (one study), pregabalin (one study) and supported early discharge (one study) compared with no intervention. For electric muscle stimulation (two studies), anabolic steroids (one study) and walking training (one study) there was a suggestion of more clinically important benefit. No concerns relating to long-term adverse events were reported. For a range of treatments there was no evidence linking them with unfavourable pain outcomes. CONCLUSIONS:To prevent chronic pain after TKR, several perioperative interventions show benefits and merit further research. Good-quality studies assessing long-term pain after perioperative interventions are feasible and necessary to ensure that patients with osteoarthritis achieve good long-term outcomes after TKR.

Dataset Information

The design and methods of genetic studies on acute and chronic postoperative pain in patients after total knee replacement.

Publications

The design and methods of genetic studies on acute and chronic postoperative pain in patients after total knee replacement.

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