The STAR care pathway for patients with chronic pain after total knee replacement: four-year follow-up of a randomised controlled trial.

BACKGROUND: The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. METHODS: Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0-10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. RESULTS: Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and - 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. CONCLUSIONS: The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. TRIAL REGISTRATION: ISRCTN: 92,545,361.

Inequalities in provision of hip and knee replacement surgery for osteoarthritis by age, sex, and social deprivation in England between 2007-2017: A population-based cohort study of the National Joint Registry.

BACKGROUND: While the United Kingdom National Health Service aimed to reduce social inequalities in the provision of joint replacement, it is unclear whether these gaps have reduced. We describe secular trends in the provision of primary hip and knee replacement surgery between social deprivation groups. METHODS AND FINDINGS: We used the National Joint Registry to identify all hip and knee replacements performed for osteoarthritis from 2007 to 2017 in England. The Index of Multiple Deprivation (IMD) 2015 was used to identify the relative level of deprivation of the patient living area. Multilevel negative binomial regression models were used to model the differences in rates of joint replacement. Choropleth maps of hip and knee replacement provision were produced to identify the geographical variation in provision by Clinical Commissioning Groups (CCGs). A total of 675,342 primary hip and 834,146 primary knee replacements were studied. The mean age was 70 years old (standard deviation: 9) with 60% and 56% of women undergoing hip and knee replacements, respectively. The overall rate of hip replacement increased from 27 to 36 per 10,000 person-years and knee replacement from 33 to 46. Inequalities of provision between the most (reference) and least affluent areas have remained constant for both joints (hip: rate ratio (RR) = 0.58, 95% confidence interval [0.56, 0.60] in 2007, RR = 0.59 [0.58, 0.61] in 2017; knee: RR = 0.82 [0.80, 0.85] in 2007, RR = 0.81 [0.80, 0.83] in 2017). For hip replacement, CCGs with the highest concentration of deprived areas had lower overall provision rates, and CCGs with very few deprived areas had higher provision rates. There was no clear pattern of provision inequalities between CCGs and deprivation concentration for knee replacement. Study limitations include the lack of publicly available information to explore these inequalities beyond age, sex, and geographical area. Information on clinical need for surgery or patient willingness to access care were unavailable. CONCLUSIONS: In this study, we found that there were inequalities, which remained constant over time, especially in the provision of hip replacement, by degree of social deprivation. Providers of healthcare need to take action to reduce this unwarranted variation in provision of surgery.

Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial.

OBJECTIVES: To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. DESIGN: Pragmatic, parallel group, open label, randomised controlled trial. SETTING: High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. PARTICIPANTS: 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). INTERVENTIONS: A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. MAIN OUTCOME MEASURES: The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups. RESULTS: The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval -8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4). CONCLUSIONS: At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN10956306.

Progression of chronic pain and associated health-related quality of life and healthcare resource use over 5 years after total knee replacement: evidence from a cohort study.

OBJECTIVE: As part of the STAR Programme, a comprehensive study exploring long-term pain after surgery, we investigated how pain and function, health-related quality of life (HRQL), and healthcare resource use evolved over 5 years after total knee replacement (TKR) for those with and without chronic pain 1 year after their primary surgery. METHODS: We used data from the Clinical Outcomes in Arthroplasty Study prospective cohort study, which followed patients undergoing TKR from two English hospitals for 5 years. Chronic pain was defined using the Oxford Knee Score Pain Subscale (OKS-PS) where participants reporting a score of 14 or lower were classified as having chronic pain 1-year postsurgery. Pain and function were measured with the OKS, HRQL using the EuroQoL-5 Dimension, resource use from yearly questionnaires, and costs estimated from a healthcare system perspective. We analysed the changes in OKS-PS, HRQL and resource use over a 5-year follow-up period. Multiple imputation accounted for missing data. RESULTS: Chronic pain was reported in 70/552 operated knees (12.7%) 1 year after surgery. The chronic pain group had worse pain, function and HRQL presurgery and postsurgery than the non-chronic pain group. Those without chronic pain markedly improved right after surgery, then plateaued. Those with chronic pain improved slowly but steadily. Participants with chronic pain reported greater healthcare resource use and costs than those without, especially 1 year after surgery, and mostly from hospital readmissions. 64.7% of those in chronic pain recovered during the following 4 years, while 30.9% fluctuated in and out of chronic pain. CONCLUSION: Although TKR is often highly beneficial, some patients experienced chronic pain postsurgery. Although many fluctuated in their pain levels and most recovered over time, identifying people most likely to have chronic pain and supporting their recovery would benefit patients and healthcare systems.

Choice between implants in knee replacement: protocol for a Bayesian network meta-analysis, analysis of joint registries and economic decision model to determine the effectiveness and cost-effectiveness of knee implants for NHS patients-The KNee Implant Prostheses Study (KNIPS).

INTRODUCTION: Knee replacements are highly successful for many people, but if a knee replacement fails, revision surgery is generally required. Surgeons and patients may choose from a range of implant components and combinations that make up knee replacement constructs, all with potential implications for how long a knee replacement will last. To inform surgeon and patient decisions, a comprehensive synthesis of data from randomised controlled trials is needed to evaluate the effects of different knee replacement implants on overall construct survival. Due to limited follow-up in trials, joint registry analyses are also needed to assess the long-term survival of constructs. Finally, economic modelling can identify cost-effective knee replacement constructs for different patient groups. METHODS AND ANALYSIS: In this protocol, we describe systematic reviews and network meta-analyses to synthesise evidence on the effectiveness of knee replacement constructs used in total and unicompartmental knee replacement and analyses of two national joint registries to assess long-term outcomes. Knee replacement constructs are defined by bearing materials and mobility, constraint, fixation and patella resurfacing. For men and women in different age groups, we will compare the lifetime cost-effectiveness of knee replacement constructs. ETHICS AND DISSEMINATION: Systematic reviews are secondary analyses of published data with no ethical approval required. We will design a common joint registry analysis plan and provide registry representatives with information for submission to research or ethics committees. The project has been assessed by the National Health Service (NHS) REC committee and does not require ethical review.Study findings will be disseminated to clinicians, researchers and administrators through open access articles, presentations and websites. Specific UK-based groups will be informed of results including National Institute for Health Research and National Institute for Health and Care Excellence, as well as international orthopaedic associations and charities. Effective dissemination to patients will be guided by our patient-public involvement group and include written lay summaries and infographics. PROSPERO REGISTRATION NUMBER: CRD42019134059 and CRD42019138015.

Choice of Prosthetic Implant Combinations in Total Hip Replacement: Cost-Effectiveness Analysis Using UK and Swedish Hip Joint Registries Data.

BACKGROUND: Prosthetic implants used in total hip replacements (THR) have a range of bearing surface combinations (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic, and metal-on-metal), head sizes (small [<36 mm in diameter] and large [≥36 mm in diameter]), and fixation techniques (cemented, uncemented, hybrid, and reverse hybrid). These can influence prosthesis survival, patients' quality of life, and healthcare costs. OBJECTIVES: To compare the lifetime cost-effectiveness of implants for patients of different age and sex profiles. METHODS: We developed a Markov model to compare the cost-effectiveness of various implants against small-head cemented metal-on-polyethylene implants. The probability that patients required 1 or more revision surgeries was estimated from analyses of more than 1 million patients in the UK and Swedish hip joint registries, for men and women younger than 55, 55 to 64, 65 to 74, 75 to 84, and 85 years and older. Implant and healthcare costs were estimated from local procurement prices, national tariffs, and the literature. Quality-adjusted life-years were calculated using published utility estimates for patients undergoing THR in the United Kingdom. RESULTS: Small-head cemented metal-on-polyethylene implants were the most cost-effective for men and women older than 65 years. These findings were robust to sensitivity analyses. Small-head cemented ceramic-on-polyethylene implants were most cost-effective in men and women younger than 65 years, but these results were more uncertain. CONCLUSIONS: The older the patient group, the more likely that the cheapest implants, small-head cemented metal-on-polyethylene implants, were cost-effective. We found no evidence that uncemented, hybrid, or reverse hybrid implants were the most cost-effective option for any patient group. Our findings can influence clinical practice and procurement decisions for healthcare payers worldwide.

Clinical- and cost-effectiveness of the STAR care pathway compared to usual care for patients with chronic pain after total knee replacement: study protocol for a UK randomised controlled trial.

BACKGROUND: Approximately 20% of patients experience chronic pain after total knee replacement. There is little evidence for effective interventions for the management of this pain, and current healthcare provision is patchy and inconsistent. Given the complexity of this condition, multimodal and individualised interventions matched to pain characteristics are needed. We have undertaken a comprehensive programme of work to develop a care pathway for patients with chronic pain after total knee replacement. This protocol describes the design of a randomised controlled trial to evaluate the clinical- and cost-effectiveness of a complex intervention care pathway compared with usual care. METHODS: This is a pragmatic two-armed, open, multi-centred randomised controlled trial conducted within secondary care in the UK. Patients will be screened at 2 months after total knee replacement and 381 patients with chronic pain at 3 months postoperatively will be recruited. Recruitment processes will be optimised through qualitative research during a 6-month internal pilot phase. Patients are randomised using a 2:1 intervention:control allocation ratio. All participants receive usual care as provided by their hospital. The intervention comprises an assessment clinic appointment at 3 months postoperatively with an Extended Scope Practitioner and up to six telephone follow-up calls over 12 months. In the assessment clinic, a standardised protocol is followed to identify potential underlying causes for the chronic pain and enable appropriate onward referrals to existing services for targeted and individualised treatment. Outcomes are assessed by questionnaires at 6 and 12 months after randomisation. The co-primary outcomes are pain severity and pain interference assessed using the Brief Pain Inventory at 12 months after randomisation. Secondary outcomes relate to resource use, function, neuropathic pain, mental well-being, use of pain medications, satisfaction with pain relief, pain frequency, capability, health-related quality of life and bodily pain. After trial completion, up to 30 patients in the intervention group will be interviewed about their experiences of the care pathway. DISCUSSION: If shown to be clinically and cost-effective, this care pathway intervention could improve the management of chronic pain after total knee replacement. TRIAL REGISTRATION: ISRCTN registry ( ISRCTN92545361 ), prospectively registered on 30 August 2016.

Health Care Needs and Support for Patients Undergoing Treatment for Prosthetic Joint Infection following Hip or Knee Arthroplasty: A Systematic Review.

BACKGROUND: Hip and knee arthroplasty are common interventions for the treatment of joint conditions, most notably osteoarthritis. Although many patients benefit from surgery, approximately 1% of patients develop infection afterwards known as deep prosthetic joint infection (PJI), which often requires further major surgery. OBJECTIVE: To assess support needs of patients undergoing treatment for PJI following hip or knee arthroplasty and to identify and evaluate what interventions are routinely offered to support such patients. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE, Web of Science, PsycINFO, Cinahl, Social Science Citation Index, The Cochrane Library, and reference lists of relevant studies from January 01, 1980 to October 05, 2016. SELECTION CRITERIA: Observational (prospective or retrospective cohort, nested case-control or case-control) studies, qualitative studies, or clinical trials conducted in patients treated for PJI and/or other major adverse occurrences following hip or knee arthroplasty. REVIEW METHODS: Data were extracted by two independent investigators and consensus was reached with involvement of a third. Given the heterogeneous nature of study designs, methods, and limited number of studies, a narrative synthesis is presented. RESULTS: Of 4,213 potentially relevant citations, we identified one case-control, one prospective cohort and two qualitative studies for inclusion in the synthesis. Patients report that PJI and treatment had a profoundly negative impact affecting physical, emotional, social and economic aspects of their lives. No study evaluated support interventions. CONCLUSION: The findings demonstrate that patients undergoing treatment for PJI have extensive physical, psychological, social and economic support needs. The interpretation of study results is limited by variation in study design, outcome measures and the small number of relevant eligible studies. However, our review highlights a lack of evidence about support strategies for patients undergoing treatment for PJI and other adverse occurrences following hip or knee arthroplasty. There is a need to design, implement and evaluate interventions to support these patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2015: CRD42015027175.

Assistive devices, hip precautions, environmental modifications and training to prevent dislocation and improve function after hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is one of the most common orthopaedic operations performed worldwide. Painful osteoarthritis of the hip is the primary indication for THA. Following THA, people have conventionally been provided with equipment, such as raised toilet seats and chairs, and educated to avoid activities that could cause the hip joint to be in a position of flexion over 90 degrees, or adduction or rotation past the midline. These aspects of occupational therapy have been advocated to reduce the risks of prosthesis dislocation. However, the appropriateness of these recommendations has been questioned. OBJECTIVES: To assess the effects of provision of assistive devices, education on hip precautions, environmental modifications and training in activities of daily living (ADL) and extended ADL (EADL) for people undergoing THA. SEARCH METHODS: We searched MEDLINE (1946 to April 2016), EMBASE (1947 to April 2016), the Cochrane Library including CENTRAL (Issue 4 of 12, 2016), Database of Reviews of Effects (DARE), Health Technology Assessment (HTA), Economic Evaluations Database (EED), CINAHL, PEDro and CIRRIE from inception to April 2016. In addition we checked Controlled Clinical Trials, Clinicaltrials.gov, the National Institutes of Health Trial Registry, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and the OpenGrey database from inception to April 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs and cluster-RCTs that evaluated the effectiveness of the provision of assistive devices, education on hip precautions, environmental modifications, or training in ADL and EADL for people undergoing THA. The main outcomes of interest were pain, function, health-related quality of life (HRQOL), global assessment of treatment success, reoperation rate, hip dislocation and adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recognised by Cochrane. We conducted a systematic literature search using several databases and contacted corresponding authors, appraised the evidence using the Cochrane risk of bias tool, analysed the data using a narrative analysis approach (as it was not possible to conduct a meta-analysis due to heterogeneity in interventions), and interpreted all outcomes using the GRADE approach. MAIN RESULTS: We included three trials with a total of 492 participants who had received 530 THA. The evidence presented with a high risk of performance, detection and reporting bias.One study (81 participants) compared outcomes for participants randomised to the provision of hip precautions, equipment and functional restrictions versus no provision of hip precautions, equipment or functional restrictions. Due to the quality of evidence being very low, we are uncertain if the provision of hip precautions, equipment and functional restrictions improved function measured using the Harris Hip Score at 12 month follow-up, or health-related quality of life (HRQOL) measured by the Short Form-12 at four week follow-up, compared to not providing this. There were no incidences of hip dislocation or adverse events in either group during the initial 12 postoperative months. The study did not measure pain score, global assessment of treatment success or total adverse events.One study (265 participants; 303 THAs) evaluated the provision of hip precautions with versus without the prescription of postoperative equipment and restrictions to functional activities. Due to the quality of evidence being very low, we are uncertain if perceived satisfaction in the rate of recovery differed in people who were not prescribed postoperative equipment and restrictions (135/151 satisfied) compared to those prescribed equipment and restrictions (113/152) (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.93; 265 participants, one trial; number needed to treat for an additional beneficial outcome (NNTB) = 7). Due to the low quality evidence, we are uncertain if the incidence of hip dislocation differed between participants provided with hip precautions with (1/152) compared to without providing equipment or restrictions post-THA (0/151) (RR 2.98, 95% CI 0.12 to 72.59). The study did not measure pain, function, HRQOL, re-operation rates or total adverse events.One study (146 participants) investigated the provision of an enhanced postoperative education and rehabilitation service on hospital discharge to promote functional ADL versus a conventional rehabilitation intervention in the community. This study was of very low quality evidence. We were uncertain if the provision of enhanced postoperative education and rehabilitation improved function at six months follow-up, when assessed using the Objective and Subjective Functional Capability Index (146 participants, one trial; P > 0.05; no numerical results provided) compared to conventional rehabilitation. The study did not measure pain score, HRQOL, global assessment of treatment success, hip dislocation, re-operation rate or total adverse events. AUTHORS' CONCLUSIONS: Very low quality evidence is available from single trials, thus we are uncertain if hip precautions with or without the addition of equipment and functional restrictions are effective in preventing dislocation and improving outcomes after THA. There is also insufficient evidence to support or refute the adoption of a postoperative community rehabilitation programme consisting of functional reintegration and education compared to conventional rehabilitation strategies based on functional outcomes.Further high-quality trials are warranted to assess the outcomes of different occupational therapy interventions both in the short and longer-term for those who undergo THA. An assessment of the impact of such interventions on pain and restriction on personal ADL, EADL and instrumental ADL is needed, and also of functional integration-type interventions rather than just hip precautions, equipment and restrictions.

Effectiveness and cost-effectiveness of outpatient physiotherapy after knee replacement for osteoarthritis: study protocol for a randomised controlled trial.

BACKGROUND: Primary total knee replacement is a common operation that is performed to provide pain relief and restore functional ability. Inpatient physiotherapy is routinely provided after surgery to enhance recovery prior to hospital discharge. However, international variation exists in the provision of outpatient physiotherapy after hospital discharge. While evidence indicates that outpatient physiotherapy can improve short-term function, the longer term benefits are unknown. The aim of this randomised controlled trial is to evaluate the long-term clinical effectiveness and cost-effectiveness of a 6-week group-based outpatient physiotherapy intervention following knee replacement. METHODS/DESIGN: Two hundred and fifty-six patients waiting for knee replacement because of osteoarthritis will be recruited from two orthopaedic centres. Participants randomised to the usual-care group (n = 128) will be given a booklet about exercise and referred for physiotherapy if deemed appropriate by the clinical care team. The intervention group (n = 128) will receive the same usual care and additionally be invited to attend a group-based outpatient physiotherapy class starting 6 weeks after surgery. The 1-hour class will be run on a weekly basis over 6 weeks and will involve task-orientated and individualised exercises. The primary outcome will be the Lower Extremity Functional Scale at 12 months post-operative. Secondary outcomes include: quality of life, knee pain and function, depression, anxiety and satisfaction. Data collection will be by questionnaire prior to surgery and 3, 6 and 12 months after surgery and will include a resource-use questionnaire to enable a trial-based economic evaluation. Trial participation and satisfaction with the classes will be evaluated through structured telephone interviews. The primary statistical and economic analyses will be conducted on an intention-to-treat basis with and without imputation of missing data. The primary economic result will estimate the incremental cost per quality-adjusted life year gained from this intervention from a National Health Services (NHS) and personal social services perspective. DISCUSSION: This research aims to benefit patients and the NHS by providing evidence on the long-term effectiveness and cost-effectiveness of outpatient physiotherapy after knee replacement. If the intervention is found to be effective and cost-effective, implementation into clinical practice could lead to improvement in patients' outcomes and improved health care resource efficiency. TRIAL REGISTRATION: ISRCTN32087234 , registered on 11 February 2015.

One-stage or two-stage revision surgery for prosthetic hip joint infection--the INFORM trial: a study protocol for a randomised controlled trial.

BACKGROUND: Periprosthetic joint infection (PJI) affects approximately 1% of patients following total hip replacement (THR) and often results in severe physical and emotional suffering. Current surgical treatment options are debridement, antibiotics and implant retention; revision THR; excision of the joint and amputation. Revision surgery can be done as either a one-stage or two-stage operation. Both types of surgery are well-established practice in the NHS and result in similar rates of re-infection, but little is known about the impact of these treatments from the patient's perspective. The main aim of this randomised controlled trial is to determine whether there is a difference in patient-reported outcome measures 18 months after randomisation for one-stage or two-stage revision surgery. METHODS/DESIGN: INFORM (INFection ORthopaedic Management) is an open, two-arm, multi-centre, randomised, superiority trial. We aim to randomise 148 patients with eligible PJI of the hip from approximately seven secondary care NHS orthopaedic units from across England and Wales. Patients will be randomised via a web-based system to receive either a one-stage revision or a two-stage revision THR. Blinding is not possible due to the nature of the intervention. All patients will be followed up for 18 months. The primary outcome is the WOMAC Index, which assesses hip pain, function and stiffness, collected by questionnaire at 18 months. Secondary outcomes include the following: cost-effectiveness, complications, re-infection rates, objective hip function assessment and quality of life. A nested qualitative study will explore patients' and surgeons' experiences, including their views about trial participation and randomisation. DISCUSSION: INFORM is the first ever randomised trial to compare two widely accepted surgical interventions for the treatment of PJI: one-stage and two-stage revision THR. The results of the trial will benefit patients in the future as the main focus is on patient-reported outcomes: pain, function and wellbeing in the long term. Patients state that these outcomes are more important than those that are clinically derived (such as re-infection) and have been commonly used in previous non-randomised studies. Results from the INFORM trial will also benefit clinicians and NHS managers by enabling the comparison of these key interventions in terms of patients' complication rates, health and social resource use and their overall cost-effectiveness. TRIAL REGISTRATION: Current controlled trials ISRCTN10956306 (registered on 29 January 2015); UKCRN ID 18159.

Promoting patient uptake and adherence in cardiac rehabilitation.

BACKGROUND: Cardiac rehabilitation is an important component of recovery from coronary events but uptake and adherence to such programs are below recommended levels. In 2010, our Cochrane review identified some evidence that interventions to increase uptake of cardiac rehabilitation can be effective but there was insufficient evidence to provide recommendations on intervention to increase adherence. In this review, we update the previously published Cochrane review. OBJECTIVES: To determine the effects, both harms and benefits, of interventions to increase patient uptake of, or adherence to, cardiac rehabilitation. SEARCH METHODS: We performed an updated search in January 2013 to identify studies published after publication of the previous systematic review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 12, 2012), MEDLINE (Ovid), EMBASE (Ovid), CINAHL EBSCO, Conference Proceedings Citation Index - Science (CPCI-S) on Web of Science (Thomson Reuters), and National Health Service (NHS) Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)) on The Cochrane Library (Issue 4, 2012). We also checked reference lists of identified systematic reviews and randomised controlled trials (RCTs) for additional studies. We applied no language restrictions. SELECTION CRITERIA: Adults with myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, heart failure, angina, or coronary heart disease eligible for cardiac rehabilitation and RCTs or quasi-randomized trials of interventions to increase uptake or adherence to cardiac rehabilitation or any of its component parts. We only included studies reporting a primary outcome. DATA COLLECTION AND ANALYSIS: At least three authors independently screened titles and abstracts of all identified references for eligibility and obtained full papers of potentially relevant trials. At least two authors checked the selection. Three authors assessed included studies for risk of bias. MAIN RESULTS: The updated search identified seven new studies (880 participants) of interventions to improve uptake of cardiac rehabilitation and one new study (260 participants) of interventions to increase adherence. When added to the previous version of this review, we included 18 studies (2505 participants), 10 studies (1338 participants) of interventions to improve uptake of cardiac rehabilitation and eight studies (1167 participants) of interventions to increase adherence. We assessed the majority of studies as having high or unclear risk of bias. Meta-analysis was not possible due to multiple sources of heterogeneity. Eight of 10 studies demonstrated increased uptake of cardiac rehabilitation. Successful interventions to improve uptake of cardiac rehabilitation included: structured nurse- or therapist-led contacts, early appointments after discharge, motivational letters, gender-specific programs, and intermediate phase programs for older patients. Three of eight studies demonstrated improvement in adherence to cardiac rehabilitation. Successful interventions included: self monitoring of activity, action planning, and tailored counselling by cardiac rehabilitation staff. Data were limited on mortality and morbidity but did not demonstrate a difference in cardiovascular events or mortality except for one study that noted an increased rate of revascularization in the intervention group. None of the studies found a difference in health-related quality of life and there was no evidence of adverse events. No studies reported on costs or healthcare utilization. AUTHORS' CONCLUSIONS: We found only weak evidence to suggest that interventions to increase the uptake of cardiac rehabilitation are effective. Practice recommendations for increasing adherence to cardiac rehabilitation cannot be made. Interventions targeting patient-identified barriers may increase the likelihood of success. Further high-quality research is still needed. 

Assessment of chronic postsurgical pain after knee replacement: a systematic review.

OBJECTIVE: Approximately 20% of patients experience chronic pain after total knee replacement (TKR), yet there is no consensus about how best to assess such pain. This systematic review aimed to identify measures used to characterize chronic pain after TKR.Methods. MEDLINE, Embase, PsycINFO, Cochrane Library, and CINAHL databases were searched for research articles published in all languages from January 2002 to November 2011. Articles were eligible for inclusion if they assessed knee pain at a minimum of 3 months after TKR, yielding a total of 1,164 articles. The data extracted included the study design,country, timings of assessments, and outcome measures containing pain items. The outcome measures were compared with domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials(IMMPACT) for inclusion in the assessment of chronic pain­related outcomes within clinical trials. Temporal trends were also explored. RESULTS: The review found use of a wide variety of composite and single-item measures, with the American Knee Society Score the most common. Many measures used in published studies did not capture the multidimensional nature of pain recommended by the IMMPACT; of those commonly used, the Western Ontario and McMaster Universities Osteoarthritis Index and Oxford Knee Score were the most comprehensive. Geographic trends were evident, with nation-specific preferences for particular measures. A recent reduction in the use of some clinically administered tools was accompanied by an increased use of patient-reported outcome measures. CONCLUSION: There was wide variation in the methods of pain assessment alongside nation-specific preferences and changing temporal trends in pain assessment after TKR. Standardization and improvements in assessment are needed to enhance the quality of research and facilitate the establishment of a core outcome set.

A systematic review of on-site monitoring methods for health-care randomised controlled trials.

BACKGROUND: Monitoring the conduct of clinical trials is recommended by International Conference of Harmonisation Good Clinical Practice (ICH GCP) guidelines and is integral to trial quality assurance. On-site monitoring, that is, visiting trial sites, is one part of this process but little is known about the procedures that are performed in practice. PURPOSE: To examine and summarise published on-site monitoring methods for health-care clinical trials, including evaluations of their benefits and costs to trials. METHODS: A systematic literature review identified all articles reporting the methods and practices of on-site monitoring of randomised controlled trials (RCTs). Articles were categorised into (1) reports from research groups and organisations, (2) reports from individual RCTs, (3) randomised trials of on-site monitoring interventions, (4) cost simulations, or (5) surveys of trial staff and monitors. Data were extracted on the characteristics of the trials and groups reporting on-site monitoring (e.g., geographical origin, sponsor, and trial focus). Information from articles in categories (1)-(3) was summarised on the frequency and scope of site monitoring visits, monitoring team size and composition, activities during site visits, and reporting structures. Evaluations of the benefits and disadvantages of on-site monitoring were examined for all included articles. RESULTS: In total, 57 articles were identified, comprising 21 articles about the on-site monitoring practices of 16 research groups, 30 articles from 26 RCTs, 1 on-site monitoring intervention RCT, 2 cost simulations, and 3 surveys. Publications in categories (1)-(3), mostly originated from the United States (33/52, 63%) or Europe (15/52, 29%), were predominantly describing non-commercial organisations or trials (45/52, 87%), with heart disease (9/26, 35%) or cancer (5/26, 19%) the commonest focus of individual RCTs. The frequency of visits ranged from every 6-8 weeks up to once every 3 years, with mostly all trial sites visited. The number of monitors visiting a site varied between 1 and 8. The most common on-site monitoring activity was verifying source data and consent forms, with a focus on data accuracy. Only six articles evaluated their on-site monitoring process, with improvements observed in recruitment rates and protocol adherence but with direct costs and staff time viewed as the major disadvantages. The on-site monitoring RCT ended prematurely so preventing full assessment. LIMITATIONS: Trialists and organisations may utilise additional unpublished on-site monitoring systems. The varied terminology used to describe monitoring may have limited identification of some relevant articles. CONCLUSIONS: This review demonstrated that on-site monitoring is utilised in trials worldwide but systems vary considerably with little evidence to support practice. These on-site monitoring practices need to be evaluated empirically, including costs, to provide robust evidence for the contribution of site visits to trial performance and quality.

Exclusion of older people from clinical trials: professional views from nine European countries participating in the PREDICT study.

BACKGROUND: There has been concern about under-representation of older people in clinical trials. The PREDICT study reported that older people and those with co-morbidity continue to be excluded unjustifiably from clinical trials. However, there is no information about differences of opinion on these issues between EU countries. The results of a survey of health-related professionals from nine EU countries that participated in the PREDICT study are presented in this study. OBJECTIVE: The aim of the study was to identify and examine any differences of opinion between EU countries on the inclusion of older patients in clinical trials. METHODS: A questionnaire using a Likert scale and free text was completed by 521 general practitioners, geriatricians, clinical researchers, ethicists, nurses and industry pharmacologists/pharmacists. The questions explored the impact of the present situation, possible reasons for under-representation and potential methods of improving participation. Countries participating were the Czech Republic, Israel, Italy, Lithuania, the Netherlands, Poland, Romania, Spain and the UK. RESULTS: There was agreement that exclusion from clinical trials on age grounds alone was unjustified (87%) and that under-representation of older people in trials caused difficulties for prescribers (79%) and patients (73%). There were national differences between professionals. All but the Lithuanians believed that older people were disadvantaged because of under-representation. The Czech, Lithuanian and Romanian professionals felt that it was justified to have age limits based on co-morbidity (61-83%) and polypharmacy (63-85%). Romanians also thought that having age limits on trial participation was justified because of reduced life expectancy (62%) and physical disability (58%) in older people. All but the Romanian professionals felt that the present arrangements for clinical trials were satisfactory (62%). All but the Israelis (56%) and Lithuanians (70%) agreed that regulation of clinical trials needed alteration. CONCLUSIONS: Although respondent selection bias cannot be excluded, the differences that emerged between countries may be the result of the political and healthcare-system differences between older and newer members of the EU. These differences may influence decision making about clinical trial regulations and practice in older people.

Bone graft substitutes in hip revision surgery: a comprehensive overview.

INTRODUCTION: Total hip replacement is increasingly used to treat diseased and damaged joints. With time, some joint replacements may require revision, mainly because of instability and mechanical loosening, and this is of particularly significance to younger patients. A major problem in revision surgery is the loss of bone stock and the consequent difficulty in reconstructing a stable joint. Loss of bone stock has been widely treated using bone autografts and allografts but supplies are limited. Use of bone graft substitutes in combination with, or as a substitute for, human bone is a possible alternative. AIM: To identify empirical studies of bone graft substitutes in hip revision surgery. METHODS: Systematic review based on Cochrane and MOOSE methods. We searched MEDLINE and EMBASE to December 2010 with terms relating to hip replacement and bone graft substitutes, and checked key citations in ISI Web of Science and reference lists. We considered all human studies irrespective of study design. RESULTS: Searches identified 397 articles. Screening of abstracts and full text articles identified 7 studies reporting outcomes of bone-graft substitute combined with autograft or allograft, and 6 studies reporting outcomes of bone graft substitute exclusively. One economic evaluation compared costs of femoral head banking with costs of bone graft substitutes. No randomised controlled trials evaluating bone graft substitute effectiveness were identified. Studies generally included small numbers of patients with a follow up too short to assess outcomes relating to implant survival. However, excepting those based on glass ceramic, ceramic bone graft substitutes show promise as an alternative to use of exclusive autograft or allograft. In the case of calcium phosphate ceramic bone graft substitute, potential cost savings were evident. CONCLUSION: With increased allograft shortage, bone graft substitutes will be required in hip revision surgery. However, appropriately designed randomised controlled trials are required to compare use of existing and new bone graft substitutes with established practice. As well as prosthesis related outcomes, studies should explore the patient experience of revision hip replacement with bone graft substitute material.

The effect of local anaesthetic wound infiltration on chronic pain after lower limb joint replacement: a protocol for a double-blind randomised controlled trial.

BACKGROUND: For the majority of patients with osteoarthritis (OA), joint replacement is a successful intervention for relieving chronic joint pain. However, between 10-30% of patients continue to experience chronic pain after joint replacement. Evidence suggests that a risk factor for chronic pain after joint replacement is the severity of acute post-operative pain. The aim of this randomised controlled trial (RCT) is to determine if intra-operative local anaesthetic wound infiltration additional to a standard anaesthesia regimen can reduce the severity of joint pain at 12-months after total knee replacement (TKR) and total hip replacement (THR) for OA. METHODS: 300 TKR patients and 300 THR patients are being recruited into this single-centre double-blind RCT. Participants are recruited before surgery and randomised to either the standard care group or the intervention group. Participants and outcome assessors are blind to treatment allocation throughout the study. The intervention consists of an intra-operative local anaesthetic wound infiltration, consisting of 60 mls of 0.25% bupivacaine with 1 in 200,000 adrenaline. Participants are assessed on the first 5 days post-operative, and then at 3-months, 6-months and 12-months. The primary outcome is the WOMAC Pain Scale, a validated measure of joint pain at 12-months. Secondary outcomes include pain severity during the in-patient stay, post-operative nausea and vomiting, satisfaction with pain relief, length of hospital stay, joint pain and disability, pain sensitivity, complications and cost-effectiveness. A nested qualitative study within the RCT will examine the acceptability and feasibility of the intervention for both patients and healthcare professionals. DISCUSSION: Large-scale RCTs assessing the effectiveness of a surgical intervention are uncommon, particularly in orthopaedics. The results from this trial will inform evidence-based recommendations for both short-term and long-term pain management after lower limb joint replacement. If a local anaesthetic wound infiltration is found to be an effective and cost-effective intervention, implementation into clinical practice could improve long-term pain outcomes for patients undergoing lower limb joint replacement. TRIAL REGISTRATION: Current Controlled Trials ISRCTN96095682.

Promoting patient uptake and adherence in cardiac rehabilitation.

BACKGROUND: Cardiac rehabilitation is an important component of recovery from coronary events but uptake and adherence to such programmes are below the recommended levels. This aim is to update a previous non-Cochrane systematic review which examined interventions that may potentially improve cardiac patient uptake and adherence in rehabilitation or its components and concluded that there is insufficient evidence to make specific recommendations. OBJECTIVES: To determine the effects of interventions to increase patient uptake of, and adherence to, cardiac rehabilitation. SEARCH STRATEGY: A previous systematic review identified studies published prior to June 2001. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 4 2007), MEDLINE (2001 to January 2008), EMBASE (2001 to January 2008), CINAHL (2001 to January 2008), PsycINFO (2001 to January 2008), Web of Science: ISI Proceedings (2001 to April 2008), and NHS Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)) from 2001 to January 2008. Reference lists of identified systematic reviews and randomised control trials (RCTs) were also checked for additional studies. SELECTION CRITERIA: Adults with myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, heart failure, angina, or coronary heart disease eligible for cardiac rehabilitation and randomised or quasi-randomised trials of interventions to increase uptake or adherence to cardiac rehabilitation or any of its component parts. Only studies reporting a measure of adherence were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts of all identified references were screened for eligibility by two reviewers independently and full papers of potentially relevant trials were obtained and checked. Included studies were assessed for risk of bias by two reviewers. MAIN RESULTS: Ten studies were identified, three of interventions to improve uptake of cardiac rehabilitation and seven of interventions to increase adherence. Meta-analysis was not possible due to multiple sources of heterogeneity. All three interventions targeting uptake of cardiac rehabilitation were effective. Two of seven studies intended to increase adherence had a significant effect. Only one study reported the non-significant effects of the intervention on cardiovascular risk factors and no studies reported data on mortality, morbidities, costs or health care resource utilisation. AUTHORS' CONCLUSIONS: There is some evidence to suggest that interventions to increase the uptake of cardiac rehabilitation can be effective. Few practice recommendations for increasing adherence to cardiac rehabilitation can be made at this time. Interventions targeting patient identified barriers may increase the likelihood of success. Further high quality research is needed.

Risk scoring in the assessment of cardiovascular risk.

PURPOSE OF REVIEW: Cardiovascular risk scoring is incorporated in guidelines and recommended for targeting preventive treatment. Evidence is required on the most appropriate method, its accuracy in a given population, and its effectiveness in favourably influencing clinical behaviour and health outcomes. RECENT FINDINGS: Recent risk scores address inaccuracies that arise when methods are transferred between populations, and specific methods and recalibrations are described for use in low-risk populations. Ethnic and social differences in risk are also recognized in the context of cardiovascular risk scoring. More sensitive measures of known risk factors and numerous emerging risk factors are reported and new statistical methods and sources of data suggested. Little emphasis has been placed on evaluation of the clinical effectiveness of cardiovascular risk scores. Education in cardiovascular risk assessment may help improve uptake of methods by healthcare professionals. SUMMARY: Numerous risk scoring methods are available to the healthcare professional but use is patchy. Accuracy varies between populations and methods have been developed to compensate for some of this variability. If risk scoring methods are to be widely used in general practice, evidence is required on both the accuracy of methods in appropriate populations and their effectiveness in improving health outcomes.