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The Cochrane Database of Systematic... Apr 2017Dietary changes are routinely recommended in people with chronic kidney disease (CKD) on the basis of randomised evidence in the general population and non-randomised... (Review)
Review
BACKGROUND
Dietary changes are routinely recommended in people with chronic kidney disease (CKD) on the basis of randomised evidence in the general population and non-randomised studies in CKD that suggest certain healthy eating patterns may prevent cardiovascular events and lower mortality. People who have kidney disease have prioritised dietary modifications as an important treatment uncertainty.
OBJECTIVES
This review evaluated the benefits and harms of dietary interventions among adults with CKD including people with end-stage kidney disease (ESKD) treated with dialysis or kidney transplantation.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register (up to 31 January 2017) through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-randomised RCTs of dietary interventions versus other dietary interventions, lifestyle advice, or standard care assessing mortality, cardiovascular events, health-related quality of life, and biochemical, anthropomorphic, and nutritional outcomes among people with CKD.
DATA COLLECTION AND ANALYSIS
Two authors independently screened studies for inclusion and extracted data. Results were summarised as risk ratios (RR) for dichotomous outcomes or mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI) or in descriptive format when meta-analysis was not possible. Confidence in the evidence was assessed using GRADE.
MAIN RESULTS
We included 17 studies involving 1639 people with CKD. Three studies enrolled 341 people treated with dialysis, four studies enrolled 168 kidney transplant recipients, and 10 studies enrolled 1130 people with CKD stages 1 to 5. Eleven studies (900 people) evaluated dietary counselling with or without lifestyle advice and six evaluated dietary patterns (739 people), including one study (191 people) of a carbohydrate-restricted low-iron, polyphenol enriched diet, two studies (181 people) of increased fruit and vegetable intake, two studies (355 people) of a Mediterranean diet and one study (12 people) of a high protein/low carbohydrate diet. Risks of bias in the included studies were generally high or unclear, lowering confidence in the results. Participants were followed up for a median of 12 months (range 1 to 46.8 months).Studies were not designed to examine all-cause mortality or cardiovascular events. In very-low quality evidence, dietary interventions had uncertain effects on all-cause mortality or ESKD. In absolute terms, dietary interventions may prevent one person in every 3000 treated for one year avoiding ESKD, although the certainty in this effect was very low. Across all 17 studies, outcome data for cardiovascular events were sparse. Dietary interventions in low quality evidence were associated with a higher health-related quality of life (2 studies, 119 people: MD in SF-36 score 11.46, 95% CI 7.73 to 15.18; I = 0%). Adverse events were generally not reported.Dietary interventions lowered systolic blood pressure (3 studies, 167 people: MD -9.26 mm Hg, 95% CI -13.48 to -5.04; I = 80%) and diastolic blood pressure (2 studies, 95 people: MD -8.95, 95% CI -10.69 to -7.21; I = 0%) compared to a control diet. Dietary interventions were associated with a higher estimated glomerular filtration rate (eGFR) (5 studies, 219 people: SMD 1.08; 95% CI 0.26 to 1.97; I = 88%) and serum albumin levels (6 studies, 541 people: MD 0.16 g/dL, 95% CI 0.07 to 0.24; I = 26%). A Mediterranean diet lowered serum LDL cholesterol levels (1 study, 40 people: MD -1.00 mmol/L, 95% CI -1.56 to -0.44).
AUTHORS' CONCLUSIONS
Dietary interventions have uncertain effects on mortality, cardiovascular events and ESKD among people with CKD as these outcomes were rarely measured or reported. Dietary interventions may increase health-related quality of life, eGFR, and serum albumin, and lower blood pressure and serum cholesterol levels.Based on stakeholder prioritisation of dietary research in the setting of CKD and preliminary evidence of beneficial effects on risks factors for clinical outcomes, large-scale pragmatic RCTs to test the effects of dietary interventions on patient outcomes are required.
Topics: Adult; Cardiovascular Diseases; Diet, Carbohydrate-Restricted; Diet, Mediterranean; Diet, Protein-Restricted; Disease Progression; Fruit; Humans; Kidney Failure, Chronic; Kidney Transplantation; Quality of Life; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Renal Replacement Therapy; Vegetables
PubMed: 28434208
DOI: 10.1002/14651858.CD011998.pub2 -
Journal of the American Academy of... Oct 2021Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma.
BACKGROUND
Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma.
OBJECTIVE
This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed.
METHODS
A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus.
RESULTS
Analysis of the evidence resulted in 18 recommendations.
LIMITATIONS
This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data.
CONCLUSIONS
Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.
Topics: Diclofenac; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Photochemotherapy
PubMed: 33820677
DOI: 10.1016/j.jaad.2021.02.082 -
Paediatrics and International Child... Nov 2018Background Pneumonia is the most common cause of death in children worldwide, accounting for 15% of all deaths of children under 5 years of age. This review summarises...
Background Pneumonia is the most common cause of death in children worldwide, accounting for 15% of all deaths of children under 5 years of age. This review summarises the evidence for the empirical antibiotic treatment of community-acquired pneumonia in neonates and children and puts emphasis on publications since the release of the previous WHO Evidence Summary report published in 2014. Methods A systematic search for systematic reviews and meta-analyses of antibiotic therapy for community-acquired pneumonia was conducted between 1 January 2013 and 10 November 2016. Results The optimal dosing recommendation for amoxicillin remains unclear with limited pharmacological and clinical evidence. There is limited evidence from surveillance to indicate whether amoxicillin or broader spectrum antibiotics (e.g. third-generation cephalosporins) are being used most commonly for paediatric CAP in different WHO regions. Data are lacking on clinical efficacy in the context of pneumococcal, staphylococcal and mycoplasma disease and the relative contributions of varying first-line and step-down options to the selection of such resistance. Conclusion Further pragmatic trials are required to optimise management of hospitalised children with severe and very severe pneumonia.
Topics: Adolescent; Amoxicillin; Anti-Bacterial Agents; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Guidelines as Topic; Humans; Infant; Infant, Newborn; Pneumonia, Bacterial; World Health Organization
PubMed: 29790844
DOI: 10.1080/20469047.2017.1409455 -
JMIR MHealth and UHealth May 2023Mobile health (mHealth) apps can promote physical activity; however, the pragmatic nature (ie, how well research translates into real-world settings) of these studies is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mobile health (mHealth) apps can promote physical activity; however, the pragmatic nature (ie, how well research translates into real-world settings) of these studies is unknown. The impact of study design choices, for example, intervention duration, on intervention effect sizes is also understudied.
OBJECTIVE
This review and meta-analysis aims to describe the pragmatic nature of recent mHealth interventions for promoting physical activity and examine the associations between study effect size and pragmatic study design choices.
METHODS
The PubMed, Scopus, Web of Science, and PsycINFO databases were searched until April 2020. Studies were eligible if they incorporated apps as the primary intervention, were conducted in health promotion or preventive care settings, included a device-based physical activity outcome, and used randomized study designs. Studies were assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) and Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) frameworks. Study effect sizes were summarized using random effect models, and meta-regression was used to examine treatment effect heterogeneity by study characteristics.
RESULTS
Overall, 3555 participants were included across 22 interventions, with sample sizes ranging from 27 to 833 (mean 161.6, SD 193.9, median 93) participants. The study populations' mean age ranged from 10.6 to 61.5 (mean 39.6, SD 6.5) years, and the proportion of males included across all studies was 42.8% (1521/3555). Additionally, intervention lengths varied from 2 weeks to 6 months (mean 60.9, SD 34.9 days). The primary app- or device-based physical activity outcome differed among interventions: most interventions (17/22, 77%) used activity monitors or fitness trackers, whereas the rest (5/22, 23%) used app-based accelerometry measures. Data reporting across the RE-AIM framework was low (5.64/31, 18%) and varied within specific dimensions (Reach=44%; Effectiveness=52%; Adoption=3%; Implementation=10%; Maintenance=12.4%). PRECIS-2 results indicated that most study designs (14/22, 63%) were equally explanatory and pragmatic, with an overall PRECIS-2 score across all interventions of 2.93/5 (SD 0.54). The most pragmatic dimension was flexibility (adherence), with an average score of 3.73 (SD 0.92), whereas follow-up, organization, and flexibility (delivery) appeared more explanatory with means of 2.18 (SD 0.75), 2.36 (SD 1.07), and 2.41 (SD 0.72), respectively. An overall positive treatment effect was observed (Cohen d=0.29, 95% CI 0.13-0.46). Meta-regression analyses revealed that more pragmatic studies (-0.81, 95% CI -1.36 to -0.25) were associated with smaller increases in physical activity. Treatment effect sizes were homogenous across study duration, participants' age and gender, and RE-AIM scores.
CONCLUSIONS
App-based mHealth physical activity studies continue to underreport several key study characteristics and have limited pragmatic use and generalizability. In addition, more pragmatic interventions observe smaller treatment effects, whereas study duration appears to be unrelated to the effect size. Future app-based studies should more comprehensively report real-world applicability, and more pragmatic approaches are needed for maximal population health impacts.
TRIAL REGISTRATION
PROSPERO CRD42020169102; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=169102.
Topics: Male; Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Exercise; Mobile Applications; Health Promotion; Telemedicine; Research Design
PubMed: 37140972
DOI: 10.2196/43162 -
CNS Drugs May 2021Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced... (Comparative Study)
Comparative Study Meta-Analysis
Real-World Evidence of the Clinical and Economic Impact of Long-Acting Injectable Versus Oral Antipsychotics Among Patients with Schizophrenia in the United States: A Systematic Review and Meta-Analysis.
BACKGROUND
Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced hospitalizations and emergency room (ER) admissions and increased medication adherence among adult patients with schizophrenia. In turn, the clinical benefits achieved may translate into lower economic burden. Real-world evidence of the comparative effectiveness of LAI is needed to understand the potential benefits of LAI outside of the context of clinical trials. This study aimed to provide a comprehensive synthesis of recent published real-world studies comparing healthcare utilization, costs, and adherence between patients with schizophrenia treated with LAI versus OA in the United States.
METHODS
In this systematic literature review, MEDLINE was searched for peer-reviewed, real-world studies (i.e., retrospective or pragmatic designs) published in English between January 1, 2010 and February 10, 2020. Comparative studies reporting hospitalizations, ER admissions, healthcare costs, or medication adherence (measured by proportion of days covered [PDC]) in adults with schizophrenia treated with LAI versus OA (or pre- vs post-LAI initiation) in the United States were retained. Random effects meta-analyses were conducted among eligible studies to evaluate the association of LAI versus OA use on hospitalizations, ER admissions, healthcare costs, and treatment adherence. A sensitivity analysis among the subset of studies that compared OA with paliperidone palmitate once monthly (PP1M), specifically, was conducted.
RESULTS
A total of 1083 articles were identified by the electronic literature search, and two publications were manually added subsequently. Among the 57 publications meeting the inclusion criteria, 25 provided sufficient information for inclusion in the meta-analyses. Compared with patients treated with OA, patients initiated on LAI had lower odds of hospitalization (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.54-0.71, n = 7), fewer hospitalizations (incidence rate ratio [IRR] [95% CI] 0.75 [0.65-0.88], n = 9), and fewer ER admissions (IRR [95% CI] 0.86 [0.77-0.97], n = 6). The initiation of LAI was associated with higher per-patient-per-year (PPPY) pharmacy costs (mean difference [MD] [95% CI] $5603 [3799-7407], n = 6), which was offset by lower PPPY medical costs (MD [95% CI] - $5404 [- 7745 to - 3064], n = 6), resulting in no significant net difference in PPPY total all-cause healthcare costs between patients treated with LAI and those treated with OA (MD [95% CI] $327 [- 1565 to 2219], n = 7). Patients initiated on LAI also had higher odds of being adherent to their medication (PDC ≥ 80%; OR [95% CI] 1.89 [1.52-2.35], n = 9). A sensitivity analysis on a subset of publications evaluating PP1M found results similar to those of the main analysis conducted at the LAI class level.
CONCLUSIONS
Based on multiple studies with varying sub-types of patient populations with schizophrenia in the United States published in the last decade, this meta-analysis demonstrated that LAI antipsychotics were associated with improved medication adherence and significant clinical benefit such as reduced hospitalizations and ER admissions compared with OA. The lower medical costs offset the higher pharmacy costs, resulting in a non-significant difference in total healthcare costs. Taken together, these findings provide strong evidence on the clinical and economic benefits of LAI compared with OA for the treatment of schizophrenia in the real world.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Emergency Service, Hospital; Health Care Costs; Hospitalization; Humans; Injections; Medication Adherence; Schizophrenia; United States
PubMed: 33909272
DOI: 10.1007/s40263-021-00815-y -
The British Journal of Surgery Aug 2015Surgical interventions are complex, with multiple components that require consideration in trial reporting. This review examines the reporting of details of surgical... (Review)
Review
BACKGROUND
Surgical interventions are complex, with multiple components that require consideration in trial reporting. This review examines the reporting of details of surgical interventions in randomized clinical trials (RCTs) within the context of explanatory and pragmatic study designs.
METHODS
Systematic searches identified RCTs of surgical interventions published in 2010 and 2011. Included studies were categorized as predominantly explanatory or pragmatic. The extent of intervention details in the reports were compared with the CONSORT statement for reporting trials of non-pharmacological treatments (CONSORT-NPT). CONSORT-NPT recommends reporting the descriptions of surgical interventions, whether they were standardized and adhered to (items 4a, 4b and 4c). Reporting of the context of intervention delivery (items 3 and 15) and operator expertise (item 15) were assessed.
RESULTS
Of 4541 abstracts and 131 full-text articles, 80 were included (of which 39 were classified as predominantly pragmatic), reporting 160 interventions. Descriptions of 129 interventions (80.6 per cent) were provided. Standardization was mentioned for 47 (29.4 per cent) of the 160 interventions, and 22 articles (28 per cent) reported measurement of adherence to at least one aspect of the intervention. Seventy-one papers (89 per cent) provided some information about context. For one-third of interventions (55, 34.4 per cent), some data were provided regarding the expertise of personnel involved. Reporting standards were similar in trials classified as pragmatic or explanatory.
CONCLUSION
The lack of detail in trial reports about surgical interventions creates difficulties in understanding which operations were actually evaluated. Methods for designing and reporting surgical interventions in RCTs, contributing to the quality of the overall study design, are required. This should allow better implementation of trial results into practice.
Topics: Guideline Adherence; Guidelines as Topic; Humans; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Research Design; Research Report; Surgical Procedures, Operative
PubMed: 26041565
DOI: 10.1002/bjs.9808 -
Frontiers in Medicine 2021Pragmatic trials inform clinical decision with better generalizability and can bridge different streams of medicine. This study collated the expectations regarding...
Pragmatic trials inform clinical decision with better generalizability and can bridge different streams of medicine. This study collated the expectations regarding pragmatic trial design of integrative medicine (IM) for diabetes and kidney diseases among patients and physicians. Dissonance between users' perspective and existing pragmatic trial design was identified. The association between risk of bias and pragmatism of study design was assessed. A 10-group semi-structured focus group interview series [21 patients, 14 conventional medicine (ConM) and 15 Chinese medicine (CM) physicians] were purposively sampled from private and public clinics in Hong Kong. Perspectives were qualitatively analyzed by constant comparative method. A systematic search of four databases was performed to identify existing IM pragmatic clinical trials in diabetes or kidney disease. Primary outcomes were the pragmatism, risk of bias, and rationale of the study design. Risk of bias and pragmatism were assessed based on Cochrane risk-of-bias tool and PRECIS-2, respectively. The correlation between risk of bias and pragmatism was assessed by regression models with sensitivity analyses. The subtheme on the motivation to seek IM service was analyzed, covering the perceived limitation of ConM effect, perceived benefits of IM service, and assessment of IM effectiveness. Patients expected IM service to retard disease progression, stabilize concomitant drug dosage, and reduce potential side effects associated with ConM. In the systematic review, 25 studies from six countries were included covering CM, Korean medicine, Ayurvedic medicine, and western herbal medicine. Existing study designs did not include a detailed assessment of concomitant drug change and adverse events. Majority of studies either recruited a non-representative proportion of patients as traditional, complementary, and integrative medicine (TCIM) diagnosis was used as inclusion criteria, or not reflecting the real-world practice of TCIM by completely dropping TCIM diagnosis in the trial design. Consultation follow-up frequency is the least pragmatic domain. Increase in pragmatism did not associate with a higher risk of bias. Existing IM pragmatic trial design does not match the patients' expectation in the analysis of incident concomitant drug change and adverse events. A two-layer design incorporating TCIM diagnosis as a stratification factor maximizes the generalizability of evidence and real-world translation of both ConM and TCIM.
PubMed: 34513860
DOI: 10.3389/fmed.2021.668913 -
PloS One 2023Consideration for patients with visual impairment, from low vision to blindness, is an important part of building a barrier-free society. Some authors have elaborated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Consideration for patients with visual impairment, from low vision to blindness, is an important part of building a barrier-free society. Some authors have elaborated that visual impairment can indeed lead to delayed development in theory of mind, thereby causing pragmatic knowledge deficiency. Verifying whether those with eye conditions have pragmatic impairment is an essential way for their clinical evaluation, intervention and rehabilitation.
OBJECTIVE
We primarily carry out a meta-analysis of visual impairment from low vision to blindness and pragmatic impairment in people with low vision or blindness to verify visual impairment may cause pragmatic impairment.
DATA SOURCES
Electronic databases Pubmed, Medline, MesH, Psychinfo, Ovid, EBSCO and CNKI and the reference sections of previous reviews.
STUDY ELIGIBILITY CRITERIA
Studies were included when they built on primary data from clinical questionnaire surveys or field trials anywhere in the world, and when they reported impacts of visual impairment on social cognition, communication, skills, behavior and intelligence. In total, 25 original studies were included, in which 25735 people were evaluated.
RESULTS
Statistically, visual impairments and pragmatic impairment exist correlation due to the significant p value(p = 0.0005 < 0.05) in group and the subgroup sorted in the light of 18 years old (p < 0.0001 and p = 0.003 < 0.05). Psychologically, because people with visual impairment can not normally get non-verbal information, they can not get a complete pragmatic knowledge system. Pragmatic knowledge deficiency leads to abnormal in executive functions and development delay from the perspective of theory of mind, inducing pragmatic impairment. Therefore, visual impairment has an impact on pragmatic impairment.
CONCLUSION
The meta-analysis reveals robust evidence on the relationship of vision impairment and pragmatic impairment in children or adults. Such evidence may help to gradually improve the clinical evaluation, intervention and rehabilitation of these people.
Topics: Child; Humans; Adolescent; Vision, Low; Intelligence; Blindness
PubMed: 38064440
DOI: 10.1371/journal.pone.0294326 -
Pain Physician Oct 2022Epidural injections are among the most commonly performed procedures for managing low back and lower extremity pain. Pinto et al and Chou et al previously performed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epidural injections are among the most commonly performed procedures for managing low back and lower extremity pain. Pinto et al and Chou et al previously performed systematic reviews and meta-analyses, which, along with a recent update from Oliveira et al showing the lack of effectiveness of epidural steroid injections in managing lumbar disc herniation, spinal stenosis, and radiculopathy. In contrast to these papers, multiple other systematic reviews and meta-analyses have supported the effectiveness and use of epidural injections utilizing fluoroscopically guided techniques. A major flaw in the review can be related to attributing active-controlled trials to placebo-controlled trials. The assumption that local anesthetics do not provide sustained benefit, despite extensive evidence that local anesthetics provide long-term relief, similar to a combination of local anesthetic with steroids is flawed.
STUDY DESIGN
The Cochrane Review of randomized controlled trials (RCTs) of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy were reanalyzed using systematic methodology and meta-analysis.
OBJECTIVES
To re-evaluate Cochrane data on RCTs of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy utilizing qualitative and quantitative techniques with dual-arm and single-arm analysis.
METHODS
In this systematic review, we have used the same RCTs from the Cochrane Review of a minimum of 20% change in pain scale or significant pain relief of >= 50%. The outcome measures were pain relief and functional status improvement. Significant improvement was defined as 50% or greater pain relief and functional status improvement. Our review was performed utilizing the Cochrane Review methodologic quality assessment and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). Evidence was summarized utilizing the principles of best evidence synthesis and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. Clinical relevance of the pragmatic nature of each study was assessed.
RESULTS
In evaluating the RCTs in the Cochrane Review, 10 trials were performed with fluoroscopic guidance. Utilizing conventional dual-arm and single-arm meta-analysis, the evidence is vastly different from the interpretation of the data within the Cochrane Review. The overall combined evidence is Level I, or strong evidence, at one and 3 months, and Level II, or moderate evidence, at 6 and 12 months.
LIMITATIONS
The limitation of this study is that only data contained in the Cochrane Review were analyzed.
CONCLUSION
A comparative systematic review and meta-analysis of the Cochrane Review of randomized controlled trials (RCTs) of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy yielded different results. This review, based on the evidence derived from placebo-controlled trials and active-controlled trials showed Level I, or strong evidence, at one and 3 months and Level II at 6 and 12 months. This review once again emphasizes the importance of the allocation of studies to placebo-control and active-control groups, utilizing standards of practice with inclusion of only the studies performed under fluoroscopic guidance.
Topics: Humans; Radiculopathy; Anesthetics, Local; Sciatica; Low Back Pain; Injections, Epidural; Steroids
PubMed: 36288577
DOI: No ID Found -
Health Technology Assessment... Mar 2023We aimed to compare the clinical effectiveness, cost-effectiveness and complication rates of total ankle replacement with those of arthrodesis (i.e. ankle fusion) in the...
BACKGROUND
We aimed to compare the clinical effectiveness, cost-effectiveness and complication rates of total ankle replacement with those of arthrodesis (i.e. ankle fusion) in the treatment of end-stage ankle osteoarthritis.
METHODS
This was a pragmatic, multicentre, parallel-group, non-blinded randomised controlled trial. Patients with end-stage ankle osteoarthritis who were aged 50-85 years and were suitable for both procedures were recruited from 17 UK hospitals and randomised using minimisation. The primary outcome was the change in the Manchester-Oxford Foot Questionnaire walking/standing domain scores between the preoperative baseline and 52 weeks post surgery.
RESULTS
Between March 2015 and January 2019, 303 participants were randomised using a minimisation algorithm: 152 to total ankle replacement and 151 to ankle fusion. At 52 weeks, the mean (standard deviation) Manchester-Oxford Foot Questionnaire walking/standing domain score was 31.4 (30.4) in the total ankle replacement arm ( = 136) and 36.8 (30.6) in the ankle fusion arm ( = 140); the adjusted difference in the change was -5.6 (95% confidence interval -12.5 to 1.4; = 0.12) in the intention-to-treat analysis. By week 52, one patient in the total ankle replacement arm required revision. Rates of wound-healing issues (13.4% vs. 5.7%) and nerve injuries (4.2% vs. < 1%) were higher and the rate of thromboembolic events was lower (2.9% vs. 4.9%) in the total ankle replacement arm than in the ankle fusion arm. The bone non-union rate (based on plain radiographs) in the ankle fusion arm was 12.1%, but only 7.1% of patients had symptoms. A post hoc analysis of fixed-bearing total ankle replacement showed a statistically significant improvement over ankle fusion in Manchester-Oxford Foot Questionnaire walking/standing domain score (-11.1, 95% confidence interval -19.3 to -2.9; = 0.008). We estimate a 69% likelihood that total ankle replacement is cost-effective compared with ankle fusion at the National Institute for Health and Care Excellence's cost-effectiveness threshold of £20,000 per quality-adjusted life-year gained over the patient's lifetime.
LIMITATIONS
This initial report contains only 52-week data, which must therefore be interpreted with caution. In addition, the pragmatic nature of the study means that there was heterogeneity between surgical implants and techniques. The trial was run across 17 NHS centres to ensure that decision-making streams reflected the standard of care in the NHS as closely as possible.
CONCLUSIONS
Both total ankle replacement and ankle fusion improved patients' quality of life at 1 year, and both appear to be safe. When total ankle replacement was compared with ankle fusion overall, we were unable to show a statistically significant difference between the two arms in terms of our primary outcome measure. The total ankle replacement versus ankle arthrodesis (TARVA) trial is inconclusive in terms of superiority of total ankle replacement, as the 95% confidence interval for the adjusted treatment effect includes both a difference of zero and the minimal important difference of 12, but it can rule out the superiority of ankle fusion. A post hoc analysis comparing fixed-bearing total ankle replacement with ankle fusion showed a statistically significant improvement of total ankle replacement over ankle fusion in Manchester-Oxford Foot Questionnaire walking/standing domain score. Total ankle replacement appears to be cost-effective compared with ankle fusion at the National Institute for Health and Care Excellence's cost-effectiveness threshold of £20,000 per quality-adjusted life-year gained over a patient's lifetime based on long-term economic modelling.
FUTURE WORK
We recommend long-term follow-up of this important cohort, in particular radiological and clinical progress. We also recommend studies to explore the sensitivity of clinical scores to detect clinically important differences between arms when both have already achieved a significant improvement from baseline.
TRIAL REGISTRATION
This trial is registered as ISRCTN60672307 and ClinicalTrials.gov NCT02128555.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 27, No. 5. See the NIHR Journals Library website for further project information.
Topics: Humans; Arthroplasty, Replacement, Ankle; Ankle; Quality of Life; Osteoarthritis; Cost-Benefit Analysis; Arthrodesis; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37022932
DOI: 10.3310/PTYJ1146