Efficacy and Safety of Adrenergic Alpha-1 Receptor Antagonists in Older Adults: A Systematic Review and Meta-analysis for the Development of Recommendations to Reduce Potentially Inappropriate Prescribing

Abstract BackgroundAdrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found.MethodsA comprehensive literature search was performed including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology. ResultsFourteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 5 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. One large observational study points at an increased risk of falls and fractures. The effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 4 out of 5 observational studies were of good quality.ConclusionsIt cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.

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Reliability of recommended non-invasive chairside screening tests for diabetes-related peripheral neuropathy: a systematic review with meta-analyses

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2021-002528 ◽

2021 ◽

Vol 9 (2) ◽

pp. e002528

Author(s):

Ally McIllhatton ◽

Sean Lanting ◽

David Lambkin ◽

Lucy Leigh ◽

Sarah Casey ◽

...

Keyword(s):

Systematic Review ◽

Peripheral Neuropathy ◽

Tuning Fork ◽

Pooled Analysis ◽

Screening Tests ◽

Cochrane Library ◽

Quality Appraisal ◽

Perception Threshold ◽

Rater Reliability ◽

Meta Analyses

The objective is to determine, by systematic review, the reliability of testing methods for diagnosis of diabetes-related peripheral neuropathy (DPN) as recommended by the most recent guidelines from the International Diabetes Foundation, International Working Group on the Diabetic Foot and American Diabetes Association. Electronic searches of Cochrane Library, EBSCO Megafile Ultimate and EMBASE were performed to May 2021. Articles were included if they reported on the reliability of recommended chairside tests in diabetes cohorts. Quality appraisal was performed using a Quality Appraisal of Reliability Studies checklist and where possible, meta-analyses, with reliability reported as estimated Cohen’s kappa (95% CI). Seventeen studies were eligible for inclusion. Pooled analysis found acceptable inter-rater reliability of vibration perception threshold (VPT) (κ=0.61 (0.50 to 0.73)) and ankle reflex testing (κ=0.60 (0.55 to 0.64)), but weak inter-rater reliability for pinprick (κ=0.45 (0.22 to 0.69)) and 128 Hz tuning fork (κ=0.42 (0.15 to 0.70)), though intra-rater reliability of the 128 Hz tuning fork was moderate (κ=0.54 (0.37 to 0.73)). Inter-rater reliability of the four-site monofilament was acceptable (κ=0.61 (0.45 to 0.77)). These results support the clinical use of VPT, ankle reflexes and four-site monofilament for screening and ongoing monitoring of DPN as recommended by the latest guidelines. The reliability of temperature perception, pinprick, proprioception, three-site monofilament and Ipswich touch test when performed in people with diabetes remains unclear.

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The Mediterranean Dietary Pattern and Inflammation in Older Adults: A Systematic Review and Meta-analysis

Advances in Nutrition ◽

10.1093/advances/nmaa116 ◽

2020 ◽

Author(s):

Pei-Yu Wu ◽

Kuei-Min Chen ◽

Wan-Chi Tsai

Keyword(s):

Systematic Review ◽

Older Adults ◽

Dietary Pattern ◽

Meta Analysis ◽

Cochrane Library ◽

Cross Sectional ◽

Mediterranean Dietary Pattern ◽

Cross Sectional Studies ◽

The Mediterranean ◽

Meta Analyses

ABSTRACT This systematic review and meta-analysis aimed to explore the association between the Mediterranean dietary pattern and inflammation in older adults. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A search of the literature was conducted up to June 2020 in 7 electronic databases, namely PubMed, Embase, Web of Science, Scopus, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ProQuest. The Joanna Briggs Institute Critical Appraisal Checklists and the Newcastle-Ottawa Scale were used to assess the methodological quality. The overall standardized mean difference (SMD) and 95% CIs were estimated in random-effects meta-analyses. Thirteen studies were identified as having acceptable quality and were included in this systematic review: 3 randomized controlled trials (RCTs), 1 quasi-experimental study, 1 cohort study, and 8 cross-sectional studies. The circulating C-reactive protein (CRP) concentration was the most common inflammation indicator used. Results of the meta-analysis on 5 cross-sectional studies revealed a significant inverse association between the Mediterranean dietary pattern and inflammation as assessed by CRP (SMD = −0.26; 95% CI: −0.41, −0.11; P < 0.001). Other studies that investigated a variety of inflammation indicators other than CRP showed mixed results with regard to the relation between the Mediterranean dietary pattern and inflammation in older adults. Our findings suggest that the Mediterranean dietary pattern may be associated with lower inflammation in older adults. However, more long-term RCTs are required to demonstrate the effects of the Mediterranean dietary pattern on multiple inflammation parameters in older adults. The study has been registered on PROSPERO (#CRD42020140145).

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Provider and LGBT Individuals’ Perspectives on LGBT Issues in Long-Term Care: A Systematic Review

The Gerontologist ◽

10.1093/geront/gnz012 ◽

2019 ◽

Vol 60 (3) ◽

pp. e169-e183 ◽

Cited By ~ 11

Author(s):

Billy A Caceres ◽

Jasmine Travers ◽

Jillian E Primiano ◽

Rachel E Luscombe ◽

Caroline Dorsen

Keyword(s):

Systematic Review ◽

Older Adults ◽

The United States ◽

Lgbt Health ◽

Term Care ◽

Lgbt Issues ◽

Services And Supports ◽

Meta Analyses ◽

Lgbt Individuals

Abstract Background and Objectives Discrimination toward the lesbian, gay, bisexual and transgender (LGBT) population has raised concerns about the type of long-term services and supports (LTSS) that will be available to them as they age. To understand the unique needs of aging LGBT populations, we sought to synthesize and critique the evidence related to LTSS providers and LGBT individuals’ perspectives of LGBT issues in LTSS in the United States. Research Design and Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review of the literature was conducted. The Crowe Critical Appraisal Tool was used to appraise the quality of the included studies. Results Nineteen studies met inclusion criteria. Seven studies that examined the perspectives of LTSS providers identified two themes, including that they lack knowledge and training on LGBT health issues and generally report negative attitudes toward same-sex relations among older adults. In addition, 12 studies that examined the perspectives of LGBT individuals found that they (i) are concerned about LTSS planning, (ii) fear discrimination from providers in LTSS, and (iii) identify several strategies for improving care of LGBT older adults receiving LTSS. Discussion and Implications This systematic review highlights the importance for LTSS providers to receive training in LGBT health and be reflective of potential biases toward the LGBT population. LGBT individuals identified concerns related to LTSS planning and fear of discrimination from LTSS providers. LGBT individuals also identified a need for increased training of providers to improve the care of LGBT older adults in LTSS.

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Effectiveness of adult community-based physical activity interventions with objective physical activity measurements and long-term follow-up: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-034541 ◽

2020 ◽

Vol 10 (5) ◽

pp. e034541

Author(s):

Charlotte Wahlich ◽

Umar A R Chaudhry ◽

Rebecca Fortescue ◽

Derek G Cook ◽

Shashivadan Hirani ◽

...

Keyword(s):

Physical Activity ◽

Systematic Review ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Community Based ◽

Intervention Effects ◽

Meta Analyses

ObjectiveTo identify randomised controlled trials (RCTs) of physical activity (PA) interventions with objective PA outcomes in adults and to evaluate whether intervention effects were sustained beyond 12 months.DesignSystematic review and meta-analysis.Data sourcesSeven databases (Medline, Embase, PsycINFO, Web of Science, Cochrane library, CINAHL (Cumulative Index of Nursing and Allied Health Literature) and ASSIA (Applied Social Sciences Index and Abstracts)) were searched from January 2000 until December 2019.Eligibility criteriaRCTs reporting objective PA outcomes beyond 12 months with community-based participants aged ≥18 years were included; those where controls received active interventions, including advice to increase PA levels, were excluded.Data extraction and synthesisTwo independent reviewers completed extraction of aggregate data and assessed risk of bias. Meta-analyses used random-effects models at different follow-up points. Primary outcomes were daily steps and weekly minutes of moderate-to-vigorous PA (MVPA).ResultsOf 33 282 records identified, nine studies (at generally low risk of bias) were included, five in meta-analyses with 12 months to 4 year follow-up. We observed 12 month increases for intervention vs control participants in steps/day (mean difference (MD)=554 (95% CIs: 384 to 724) p<0.0001, I2=0%; 2446 participants; four studies) and weekly MVPA minutes (MD=35 (95% CI: 27 to 43) p<0.0001, I2=0%; 2647 participants; four studies). Effects were sustained up to 4 years for steps/day (MD=494 (95% CI: 251 to 738) p<0.0001, I2=0%; 1944 participants; four studies) and weekly MVPA minutes (MD=25 (95% CI: 13 to 37) p<0.0001, I2=0%; 1458 participants; three studies).ConclusionsThere are few PA interventions with objective follow-up beyond 12 months, more studies are needed. However, this review provided evidence of PA intervention effects beyond 12 months and sustained up to 4 years for both steps/day and MVPA. These findings have important implications for potential long-term health benefits.PROSPERO registration numberCRD42017075753.

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Long-term safety of prenatal and neonatal exposure to paracetamol: a protocol for a systematic review

BMJ Paediatrics Open ◽

10.1136/bmjpo-2020-000907 ◽

2020 ◽

Vol 4 (1) ◽

pp. e000907

Author(s):

Samira Samiee-Zafarghandy ◽

Katelyn Sushko ◽

John Van Den Anker

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Systematic Reviews ◽

Evidence Synthesis ◽

Knowledge Exchange ◽

Newborn Infants ◽

Assessment Tools ◽

Neonatal Exposure ◽

Meta Analyses

IntroductionA surge in the use of paracetamol in neonates has resulted in growing concerns about its potential long-term adverse events. In this study, we conduct a systematic review of the long-term safety of prenatal and neonatal exposure to paracetamol in newborn infants.Methods and analysisWe will follow the Joanna Briggs Institute Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements to conduct and report this review. We will conduct a systematic search of Embase, MEDLINE, Web of Science and Google Scholar for studies with data on long-term adverse events in neonates that were exposed to paracetamol in the prenatal and/or neonatal period. We will not apply language or design limitations. We will use standardised risk of bias assessment tools to perform a quality assessment of each included article.Ethics and disseminationThis systematic review will only involve access to publicly available data, and therefore ethical approval will not be required. The results of this study will be communicated to the target audience through peer-reviewed publication as well as other knowledge exchange platforms, such as conferences, congresses or symposia.Trial registrationThe protocol for this systematic review is submitted for registration to international database of prospectively registered systematic reviews (PROSPERO, awaiting registration number).

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The Effectiveness of Biographical Approaches in Long-Term Care: A Systematic Review

The Gerontologist ◽

10.1093/geront/gnz074 ◽

2019 ◽

Vol 60 (4) ◽

pp. e309-e328

Author(s):

Lara Menn ◽

Sabine Corsten ◽

Norina Lauer ◽

Sarah J Wallace

Keyword(s):

Systematic Review ◽

Older Adults ◽

Narrative Analysis ◽

Aged Care ◽

Research Literature ◽

Residential Aged Care ◽

Cochrane Library ◽

Term Care ◽

Care Experience

Abstract Background and Objectives Older adults in long-term residential aged care experience loneliness and reduced quality of life (QoL). Biographical approaches use the recall of the past events to increase self-efficacy, promote acceptance, and improve QoL. The aim of the systematic review was to examine the effectiveness of biographical approaches in improving the QoL of older adults in long-term residential aged care. Research Design and Methods This systematic review was conducted in accordance with PRISMA guidelines, using databases Medline, CINAHL, and the Cochrane Library. A 2-phase search strategy was used to identify research literature relating to the use of biographical interventions. Narrative analysis was used to synthesize results. Results Twenty-one studies met inclusion criteria for this review, comprising both group and individual interventions. The findings were inconsistent. Subjective elements of QoL of older adults improved in a narrow majority of the studies. Of a total of 21 outcomes investigated in group interventions, 11 resulted in significant improvements in QoL. The 16 outcomes of the individual interventions resulted in 10 significant improvements. The most significant influence was observed in life satisfaction. Group reminiscence also had a particularly strong influence on self-esteem. Discussion and Implications Although benefits were observed, it remains unclear why some interventions led to improvements in subjective elements of QoL and others did not. Exploration of the participant perspective through qualitative data collection and more detailed description of interventions in future studies could lead to a better understanding of the treatment components that are related to improved outcomes for older adults.

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System Immersion in Virtual Reality-Based Rehabilitation of Motor Function in Older Adults: A Systematic Review and Meta-Analysis

Frontiers in Virtual Reality ◽

10.3389/frvir.2021.647993 ◽

2021 ◽

Vol 2 ◽

Author(s):

Emil Rosenlund Høeg ◽

Tina Myung Povlsen ◽

Jon Ram Bruun-Pedersen ◽

Belinda Lange ◽

Niels Christian Nilsson ◽

...

Keyword(s):

Systematic Review ◽

Older Adults ◽

Virtual Reality ◽

Video Games ◽

Adverse Events ◽

Outcome Measures ◽

Meta Analysis ◽

Virtual Rehabilitation ◽

Meta Analyses ◽

Ivr Systems

Background: As the elderly population continues to grow, so does the demand for new and innovative solutions to tackle age-related chronic diseases and disabilities. Virtual Reality (VR) has been explored as a novel therapeutic tool for numerous health-related applications. Although findings frequently favors VR, methodological shortcomings prevent clinical recommendations. Moreover, the term “VR” is frequently used ambiguously to describe e.g., video games; the distinction remains vague between immersive VR (IVR) systems and non-immersive VR (NVR). With no distinct demarcation, results of outcome measures are often pooled in meta-analyses, without accounting for the immersiveness of the system.Objective: This systematic review focused on virtual reality-based rehabilitation of older adults (+60) in motor rehabilitation programs. The review aims to retrospectively classify previous studies according to the level of immersion, in order to get an overview of the ambiguity-phenomenon, and to utilize meta-analyses and subgroup analyses to evaluate the comparative efficacy of system immersion in VR-based rehabilitation.Methods: Following PRISMA guidelines, we conducted a systematic search for randomized controlled trials, describing virtual rehabilitation or video games interventions for older adults (+60). Main outcomes were pain, motivation, mobility, balance, and adverse events.Results: We identified 15 studies which included 743 patients. Only three studies utilized IVR. The rest used various NVR-equipment ranging from commercial products (e.g., Nintendo Wii), to bespoke systems that combine tracking devices, software, and displays. A random effects meta-analysis of 10 studies analyzed outcome measures of mobility, balance, and pain. Protocols and dosage varied widely, but outcome results were in favor of immersive and non-immersive interventions, however, dropout rates and adverse events were mostly in favor of the control.Conclusions: We initialize a call-for-action, to distinguish between types of VR-technology and propose a taxonomy of virtual rehabilitation systems based on our findings. Most interventions use NVR-systems, which have demonstrably lower cybersickness-symptoms than IVR-systems. Therefore, adverse events may be under-reported in RCT-studies. An increased demand for IVR-systems highlight this challenge. Care should be given, when applying the results of existing NVR tools to new IVR-technologies. Future studies should provide more detail about their interventions, and future reviews should differentiate between NVR and IVR.

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Low Protein Intake Is Associated with Frailty in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies

Nutrients ◽

10.3390/nu10091334 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1334 ◽

Cited By ~ 26

Author(s):

Hélio Coelho-Júnior ◽

Bruno Rodrigues ◽

Marco Uchida ◽

Emanuele Marzetti

Keyword(s):

Systematic Review ◽

Older Adults ◽

Protein Intake ◽

Observational Studies ◽

Meta Analysis ◽

Cochrane Library ◽

Cross Sectional ◽

Frailty Status ◽

Search Terms ◽

Meta Analyses

(1) Background: Several factors have been suggested to be associated with the physiopathology of frailty in older adults, and nutrition (especially protein intake) has been attributed fundamental importance in this context. The objective of this study was to conduct a systematic review and meta-analysis to investigate the relationship between protein intake and frailty status in older adults. (2) Methods: A search of scientific studies was conducted in the main databases (Medline, Scopus, Cochrane library), and in the reference lists of selected articles. The search terms included synonyms and Medical Subject Headings and involved the use of Boolean operators which allowed the combination of words and search terms. Observational studies—cross-sectional and longitudinal—that met the eligibility criteria were included in the review. Article selection and data extraction were performed by two independent reviewers. Meta-analyses with random effects were performed. Publication bias was measured using the Strengthening the Reporting of Observational Studies in Epidemiology instrument. (3) Results: In the final sample, 10 articles, seven cross-sectional and three longitudinal, were included in the present study. Overall, studies investigated a total of 50,284 older adults from three different continents between 2006 and 2018. Four cross-sectional studies were included in the meta-analyses. The results demonstrated that a high protein intake was negatively associated with frailty status in older adults (odds ratio: 0.67, confidence interval = 0.56 to 0.82, p = 0.0001). (4) Conclusions: Our findings suggest that a high consumption of dietary protein is inversely associated with frailty in older adults.

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Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis

PLoS Medicine ◽

10.1371/journal.pmed.1003524 ◽

2021 ◽

Vol 18 (3) ◽

pp. e1003524

Author(s):

Latha Velayudhan ◽

Katie McGoohan ◽

Sagnik Bhattacharyya

Keyword(s):

Systematic Review ◽

Older Adults ◽

Adverse Events ◽

Meta Analysis ◽

Synthetic Cannabinoids ◽

The Elderly ◽

Outcome Data ◽

Cochrane Library ◽

Qualitative Synthesis ◽

Increased Risk

Background Cannabinoid-based medicines (CBMs) are being used widely in the elderly. However, their safety and tolerability in older adults remains unclear. We aimed to conduct a systematic review and meta-analysis of safety and tolerability of CBMs in adults of age ≥50 years. Methods and findings A systematic search was performed using MEDLINE, PubMed, EMBASE, CINAHL PsychInfo, Cochrane Library, and ClinicalTrials.gov (1 January 1990 to 3 October 2020). Randomised clinical trials (RCTs) of CBMs in those with mean age of ≥50 years for all indications, evaluating the safety/tolerability of CBMs where adverse events have been quantified, were included. Study quality was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two reviewers conducted all review stages independently. Where possible, data were pooled using random-effects meta-analysis. Effect sizes were calculated as incident rate ratio (IRR) for outcome data such as adverse events (AEs), serious AEs (SAEs), and death and risk ratio (RR) for withdrawal from study and reported separately for studies using tetrahydrocannabinol (THC), THC:cannabidiol (CBD) combination, and CBD. A total of 46 RCTs were identified as suitable for inclusion of which 31 (67%) were conducted in the United Kingdom and Europe. There were 6,216 patients (mean age 58.6 ± 7.5 years; 51% male) included in the analysis, with 3,469 receiving CBMs. Compared with controls, delta-9-tetrahydrocannabinol (THC)-containing CBMs significantly increased the incidence of all-cause and treatment-related AEs: THC alone (IRR: 1.42 [95% CI, 1.12 to 1.78]) and (IRR: 1.60 [95% CI, 1.26 to 2.04]); THC:CBD combination (IRR: 1.58 [95% CI,1.26 to 1.98]) and (IRR: 1.70 [95% CI,1.24 to 2.33]), respectively. IRRs of SAEs and deaths were not significantly greater under CBMs containing THC with or without CBD. THC:CBD combination (RR: 1.40 [95% CI, 1.08 to 1.80]) but not THC alone (RR: 1.18 [95% CI, 0.89 to 1.57]) significantly increased risk of AE-related withdrawals. CBD alone did not increase the incidence of all-cause AEs (IRR: 1.02 [95% CI, 0.90 to 1.16]) or other outcomes as per qualitative synthesis. AE-related withdrawals were significantly associated with THC dose in THC only [QM (df = 1) = 4.696, p = 0.03] and THC:CBD combination treatment ([QM (df = 1) = 4.554, p = 0.033]. THC-containing CBMs significantly increased incidence of dry mouth, dizziness/light-headedness, and somnolence/drowsiness. Study limitations include inability to fully exclude data from those <50 years of age in our primary analyses as well as limitations related to weaknesses in the included trials particularly incomplete reporting of outcomes and heterogeneity in included studies. Conclusions This pooled analysis, using data from RCTs with mean participant age ≥50 years, suggests that although THC-containing CBMs are associated with side effects, CBMs in general are safe and acceptable in older adults. However, THC:CBD combinations may be less acceptable in the dose ranges used and their tolerability may be different in adults over 65 or 75 years of age.

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Are perioperative interventions effective in preventing chronic pain after primary total knee replacement? A systematic review

BMJ Open ◽

10.1136/bmjopen-2018-028093 ◽

2019 ◽

Vol 9 (9) ◽

pp. e028093 ◽

Cited By ~ 2

Author(s):

Andrew David Beswick ◽

Jane Dennis ◽

Rachael Gooberman-Hill ◽

Ashley William Blom ◽

Vikki Wylde

Keyword(s):

Systematic Review ◽

Chronic Pain ◽

Adverse Events ◽

Total Knee Replacement ◽

Knee Replacement ◽

Risk Of Bias ◽

Low Risk ◽

Cochrane Library ◽

Total Knee

ObjectivesFor 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.MethodsWe conducted a systematic review of perioperative interventions for adults with osteoarthritis receiving primary TKR evaluated in a randomised controlled trial (RCT). We searchedThe 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.InterventionsPerioperative non-surgical interventions; control receiving no intervention or alternative treatment.Primary and secondary outcome measuresPain or score with pain component assessed at 6 months or longer postoperative.Results44 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.ConclusionsTo 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.

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