Recent Submissions

  • Resveratrol for the management of human health: how far have we come? A systematic review of resveratrol clinical trials to highlight gaps and opportunities

    Brown, Karen; Pepper, Coral (2024-01-06)
    Resveratrol has long been proposed as being beneficial to human health across multiple morbidities, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. A large cohort with high-quality clinical data and clearly defined biomarkers or endpoints are required to draw meaningful conclusions. This systematic review compiles every clinical trial conducted using a defined dose of resveratrol in a purified form across multiple morbidities to highlight the current 'state-of-play' and knowledge gaps, informing future trial designs to facilitate the realisation of resveratrol's potential benefits to human health. Over the last 20 years, there have been almost 200 studies evaluating resveratrol across at least 24 indications, including cancer, menopause symptoms, diabetes, metabolic syndrome, and cardiovascular disease. There are currently no consensus treatment regimens for any given condition or endpoint, beyond the fact that resveratrol is generally well-tolerated at a dose of up to 1 g/day. Additionally, resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, over the last 20 years, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required to transition this intriguing compound from health food shops to the clinic.
  • Effect of aerobic exercise training on pulse wave velocity in adults with and without long-term conditions: a systematic review and meta-analysis

    Daynes, Enya; Divall, Pip; Evans, Rachael Andrea; Graham-Brown, Matthew; Latimer, Lorna; McCann, Gerry P; Steiner, Michael C; Ward, Thomas J.C. (2023-12-14)
    Rationale: There is conflicting evidence whether aerobic exercise training (AET) reduces pulse wave velocity (PWV) in adults with and without long-term conditions (LTCs). Objective: To explore whether PWV improves with AET in adults with and without LTC, to quantify the magnitude of any effect and understand the influence of the exercise prescription. Data sources: CENTRAL, MEDLINE and EMBASE were among the databases searched. Eligibility criteria: We included studies with a PWV measurement before and after supervised AET of at least 3 weeks duration. Exclusion criteria included resistance exercise and alternative measures of arterial stiffness. Design: Controlled trials were included in a random effects meta-analysis to explore the effect of AET on PWV. Uncontrolled studies were included in a secondary meta-analysis and meta-regression exploring the effect of patient and programme factors on change in PWV. The relevant risk of bias tool was used for each study design. Results: 79 studies (n=3729) were included: 35 controlled studies (21 randomised control trials (RCT) (n=1240) and 12 non-RCT (n=463)) and 44 uncontrolled (n=2026). In the controlled meta- analysis, PWV was significantly reduced following AET (mean (SD) 11 (7) weeks) in adults with and without LTC (mean difference -0.63; 95% CI -0.82 to -0.44; p<0.0001). PWV was similarly reduced between adults with and without LTC (p<0.001). Age, but not specific programme factors, was inversely associated with a reduction in PWV -0.010 (-0.020 to -0.010) m/s, p<0.001. Discussion: Short-term AET similarly reduces PWV in adults with and without LTC. Whether this effect is sustained and the clinical implications require further investigation.
  • Clinimetrics of performance-based functional outcome measures for vascular amputees: A systematic review

    Daynes, Enya; Houghton, John; Sayers, Robert; Pepper, Coral; Singh, Sally (2023-06-03)
    Background: Objective physical performance-based outcome measures (PerBOMs) are essential tools for the holistic management of people who have had an amputation due to vascular disease. These people are often non-ambulatory, however it is currently unclear which PerBOMs are high quality and appropriate for those who are either ambulatory or non-ambulatory. Research question: Which PerBOMs have appropriate clinimetric properties to be recommended for those who have had amputations due to vascular disease ('vascular amputee')? Data sources: MEDLINE, CINAHL, EMBASE, EMCARE, the Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus databases were searched for the terms: "physical performance" or "function", "clinimetric properties", "reliability", "validity", "amputee" and "peripheral vascular disease" or "diabetes". Review methods: A systematic review of PerBOMs for vascular amputees was performed following COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology and PRISMA guidelines. The quality of studies and individual PerBOMs was assessed using COSMIN risk of bias and good measurement properties. Overall PerBOM quality was evaluated with a modified GRADE rating. Key clinimetric properties evaluated were reliability, validity, predictive validity and responsiveness. Results: A total of 15,259 records were screened. Forty-eight studies (2650 participants) were included: 7 exclusively included vascular amputees only, 35 investigated validity, 20 studied predictive validity, 23 investigated reliability or internal consistency and 7 assessed responsiveness. Meta-analysis was neither possible nor appropriate for this systematic review in accordance with COSMIN guidelines, due to heterogeneity of the data. Thirty-four different PerBOMs were identified of which only 4 are suitable for non-ambulatory vascular amputees. The Amputee Mobility Predictor no Prosthesis (AMPnoPro) and Transfemoral Fitting Predictor (TFP) predict prosthesis use only. PerBOMs available for assessing physical performance are the One-Leg Balance Test (OLBT) and Basic Amputee Mobility Score (BAMS). Conclusion: At present, few PerBOMs can be recommended for vascular amputees. Only 4 are available for non-ambulatory individuals: AMPnoPro, TFP, OLBT and BAMS.
  • The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis

    Faulkner, Lucy; Pepper, Coral; Thomas, Anne (2022-11-08)
    Introduction: Colorectal cancer is the fourth most common cancer in the UK. There remains a need for improved risk stratification following curative resection. Circulating-tumour DNA (ctDNA) has gained particular interest as a cancer biomarker in recent years. We performed a systematic review to assess the utility of ctDNA in identifying minimal residual disease in colorectal cancer. Methods: Studies were included if ctDNA was measured following curative surgery and long-term outcomes were assessed. Studies were excluded if the manuscript could not be obtained from the British Library or were not available in English. Results: Thirty-seven studies met the inclusion criteria, involving 3002 patients. Hazard ratios (HRs) for progression-free survival (PFS) were available in 21 studies. A meta-analysis using a random effects model demonstrated poorer PFS associated with ctDNA detection at the first liquid biopsy post-surgery [HR: 6.92 CI: 4.49-10.64 p < 0.00001]. This effect was also seen in subgroup analysis by disease extent, adjuvant chemotherapy and assay type. Discussion: Here we demonstrate that ctDNA detection post-surgery is associated with a greater propensity to disease relapse and is an independent indicator of poor prognosis. Prior to incorporation into clinical practice, consensus around timing of measurements and assay methodology are critical. Protocol registration: The protocol for this review is registered on PROSPERO (CRD42021261569).
  • Fibular- versus tibiofibular-based reconstruction of the posterolateral corner of the knee: A systematic review and meta-analysis

    Boksh, Khalis; Ghosh, Arijit; Narayan, Prithish; Divall, Pip; Aujla, Randeep
    Background: Fibular- and tibiofibular-based reconstructions are the gold standard treatment for posterolateral corner (PLC) injuries of the knee. Despite comparable outcomes in biomechanical studies, clinical results comparing these constructs remain elusive with no consensus reached regarding the best treatment option. Purpose: To perform a systematic review and meta-analysis to compare fibular- and tibiofibular-based techniques for posterolateral corner reconstruction. We aimed to identify whether any differences existed between the 2 techniques in terms of clinical outcomes and rotational and varus stability. Study design: Meta-analysis; Level of evidence, 4. Methods: The Cochrane Controlled Register of Trials, PubMed, Medline, and Embase were used to perform a systematic review and meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria with the following search terms ("posterolateral corner" OR "fibular collateral ligament" OR "lateral collateral ligament" OR "popliteus tendon" OR "popliteofibular ligament") AND ("reconstruction" OR "LaPrade" OR "Larson" OR "Arciero"). Data pertaining to all patient-reported outcome measures (PROMs), postoperative complications, and valgus and rotational stability were extracted from each study. The pooled outcome data were analyzed by random- and fixed-effects models. Results: After abstract and full-text screening, 6 clinical studies were included. In total, there were 183 patients, of which 90 received fibular-based and 93 tibiofibular-based reconstruction. The majority of studies used similar surgical techniques regarding tunnel orientation, attachment sites, and graft fixation sequence. There were no differences between the groups in terms of PROMs and subjective knee scores at a mean of 20.3 months. The techniques were equally effective in restoring varus and rotational stability. Subgroup analysis revealed that the stability of a posterior cruciate ligament reconstruction postoperatively was not affected by either construct. Conclusion: Both constructs had comparable clinical outcomes and were equally effective in restoring varus and rotational stability for PLC knee injuries. The fibular-based technique may offer advantages in view of being less technically demanding and invasive and requiring fewer grafts with a quicker operative time. However, higher quality studies are required to reinforce or refute such conclusions, as the majority of studies in this review were poor to fair quality.
  • National policies for delivering tuberculosis, HIV and hepatitis B and C virus infection services for refugees and migrants among Member States of the WHO European Region

    Nazareth, Joshua; Divall, Pip; Pan, Daniel; Martin, Christopher; Pareek, Manish (2022-11-25)
    Background/objective: Refugees and migrants to the World Health Organization (WHO) European Region are disproportionately affected by infections, including tuberculosis (TB), human immunodeficiency virus (HIV) and hepatitis B and C (HBV/HCV) compared with the host population. There are inequities in the accessibility and quality of health services available to refugees and migrants in the Region. This has consequences for health outcomes and will ultimately impact the ability to meet Regional infection elimination targets. Methods: We reviewed academic and grey literature to identify national policies and guidelines for TB/HIV/HBV/HCV specific to refugees and migrants in the Member States of the WHO European Region and to identify: (i) evidence informing policy and (ii) barriers and facilitators to policy implementation. Results: Relatively few primary national policy/guideline documents were identified which related to refugees and migrants and TB [14 of 53 Member States (26%), HIV (n = 15, 28%) and HBV/HCV (n = 3, 6%)], which often did not align with the WHO recommendations, and for some countries, violated refugees' and migrants' human rights. We found extreme heterogeneity in the implementation of the WHO- and European Centre for Disease Prevention and Control (ECDC)-advocated policies and recommendations on the prevention, diagnosis, treatment and care of TB/HIV/HBV/HCV infection among migrants across the Member States of the WHO European Region.There is great heterogeneity in implementation of WHO- and ECDC-advocated policies on the prevention, diagnosis, treatment and care of TB/HIV/HBV/HCV infection in refugees and migrants across the Member States in the Region. Conclusion: More transparent and accessible reporting of national policies and guidelines are required, together with the evidence base upon which these policy decisions are based. Political engagement is essential to drive the changes in national legislation to ensure equitable and universal access to the diagnosis and care for infectious diseases.
  • Platelet-rich plasma in acute Achilles tendon ruptures: A systematic review and meta-analysis

    Boksh, Khalis; Elbashir, Mohamed; Divall, Pip; Mangwani, Jitendra (2022-03-16)
    Background: Platelet Rich Plasma (PRP) is known to exert multi-directional biological effects favouring tendon healing. However, conclusions drawn by numerous studies on its clinical efficacy for acute Achilles tendon rupture are limited. We performed a systematic review and meta-analysis to investigate this and to compare to those without PRP treatment. Methods: The Cochrane Controlled Register of Trials, Pubmed, Medline and Embase were used and assessed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria with the following search terms: ('plasma' OR 'platelet-rich' OR 'platelet-rich plasma' or 'PRP') AND ('Achilles tendon rupture/tear' OR 'calcaneal tendon rupture/tear' OR 'tendo calcaneus rupture/tear'). Data pertaining to biomechanical outcomes (heel endurance test, isokinetic strength, calf-circumference and range of motion), patient-reported outcome measures (PROMs) and incidence of re-ruptures were extracted. Meta-analysis was performed for same outcomes measured in at least three studies. Pooled outcome data were analysed by random- and fixed-effects models. Results: After abstract and full-text screening, 6 studies were included. In total there were 510 patients of which 256 had local PRP injection and 254 without. The average age was 41.6 years, mean time from injury to treatment 5.9 days and mean follow-up at 61 weeks. Biomechanically, there was similar heel endurance, isokinetic strength, calf circumference and range of motion between both groups. In general, there were no differences in patient reported outcomes from all scoring systems used in the studies. Both groups returned to their pre-injured level at a similar time and there were no differences on the incidence of re-rupture (OR 1.13, 95% CI, 0.46-2.80, p = 0.79). Conclusion: PRP injections for acute Achilles tendon ruptures do not improve medium to long-term biomechanical and clinical outcomes. However, future studies incorporating the ideal application and biological composition of PRP are required to investigate its true clinical efficacy.
  • Effect of high-pain versus low-pain structured exercise on walking ability in people with intermittent claudication: meta-analysis

    Zaccardi, Francesco; Houghton, John; Pepper, Coral; Rayt, Harjeet; Sayers, Robert (2022-05-12)
    Background: The aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC). Methods: A network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched. Trials were included if they were: RCTS; involved adults with IC; had at least two of the following arms-structured low-pain exercise, structured high--pain exercise or usual-care control; and a maximal or pain-free treadmill walking outcome. Results: Some 14 trials were included; results were pooled using the standardized mean difference (MD). Structured low-pain exercise had a significant large positive effect on MWA (MD 2.23, 95 percent c.i. 1.11 to 3.35) and PFWA (MD 2.26, 1.26 to 3.26) compared with usual-care control. Structured high-pain exercise had a significant large positive effect on MWA (MD 0.95, 0.20 to 1.70) and a moderate positive effect on PFWA (0.77, 0.01 to 1.53) compared with usual-care control. In an analysis of structured low- versus high pain exercise, there was a large positive effect in favour of low-pain exercise on MWA (MD 1.28, -0.07 to 2.62) and PFWA (1.50, 0.24 to 2.75); however, this was significant only for PFWA. Conclusion: There is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control (unstructured exercise advice).
  • Systematic review of physical activity, sedentary behaviour and sleep among adults living with chronic respiratory disease in low- and middle-income countries

    Singh, Sally; Divall, Pip (2022-04-18)
    Abstract: Physical activity (PA), sedentary behaviour (SB) and sleep are important lifestyle behaviours associated with chronic respiratory disease (CRD) morbidity and mortality. These behaviours need to be understood in low- and middle-income countries (LMIC) to develop appropriate interventions. Purpose: Where and how have free-living PA, SB and sleep data been collected for adults living with CRD in LMIC? What are the free-living PA, SB and sleep levels of adults living with CRD? Patients and methods: The literature on free-living PA, SB and sleep of people living with CRD in LMIC was systematically reviewed in five relevant scientific databases. The review included empirical studies conducted in LMIC, reported in any language. Reviewers screened the articles and extracted data on prevalence, levels and measurement approach of PA, SB and sleep using a standardised form. Quality of reporting was assessed using bespoke criteria. Results: Of 89 articles, most were conducted in Brazil (n=43). PA was the commonest behaviour measured (n=66). Questionnaires (n=52) were more commonly used to measure physical behaviours than device-based (n=37) methods. International Physical Activity Questionnaire was the commonest for measuring PA/SB (n=11). For sleep, most studies used Pittsburgh Sleep Quality Index (n=18). The most common ways of reporting were steps per day (n=21), energy expenditure (n=21), sedentary time (n=16), standing time (n=13), sitting time (n=11), lying time (n=10) and overall sleep quality (n=32). Studies revealed low PA levels [steps per day (range 2669-7490steps/day)], sedentary lifestyles [sitting time (range 283-418min/day); standing time (range 139-270min/day); lying time (range 76-119min/day)] and poor sleep quality (range 33-100%) among adults with CRD in LMIC. Conclusion: Data support low PA levels, sedentary lifestyles and poor sleep among people in LMIC living with CRDs. More studies are needed in more diverse populations and would benefit from a harmonised approach to data collection for international comparisons.
  • Selecting portable ankle/toe brachial pressure index systems for a peripheral arterial disease population screening programme: a systematic review, clinical evaluation exercise, and consensus process

    Patel, Bhavisha; Katsogridakis, Emmanuel; Pepper, Coral; Messeder, Sarah; Saratzis, Athanasios; Nicholls, Jennifer; Bown, Matthew (2022-08-12)
    Objective: To provide an overview of systems available for peripheral arterial disease (PAD) screening, together with respective accuracies and a clinical evaluation to identify a system suitable for use in a community screening programme. Methods: A systematic review of the diagnostic accuracy of six ankle brachial pressure index (ABPI) and toe brachial pressure index (TBPI) devices deemed to be portable, which were Conformité Européenne (CE) marked, and were automated or semi-automated was carried out compared with gold standard handheld Doppler and duplex ultrasound. The devices were MESI-ABPI-MD, Huntleigh Dopplex Ability, Huntleigh ABPI and TBPI systems, Systoe TBPI system, and BlueDop. Seven databases (MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) were searched, and 11 studies were identified as eligible for review. This was followed by hands on clinical evaluation by abdominal aortic aneurysm (AAA) screening staff (n = 39). During this, devices were demonstrated to staff which they then tested on volunteers and gave feedback using pre-designed questionnaires on their suitability for use in a screening programme. Finally, accuracy data and staff preferences were combined during a consensus conference that was held between study and screening staff to determine the most appropriate device to use in a community screening programme. Results: Generally, the evaluated systems have a moderate level of sensitivity and a high level of specificity: Dopplex ability sensitivity 20% - 70%, specificity 86% - 96%; MESI sensitivity 57% - 74%, specificity 85% - 99%; BlueDop sensitivity 95%, specificity 89%; and Systoe sensitivity 71%, specificity 77%. Clinical evaluation by screening staff identified a preference for the MESI system. The consensus conference concluded that the MESI device was a good candidate for use in a community PAD screening programme. Conclusion: The MESI system is a good candidate to consider for community PAD screening.
  • NHS librarians collaborate to develop a search bank peer reviewing and sharing COVID-19 searches: an evaluation

    Divall, Pip (2022-07-09)
    Background: Responding to the COVID-19 pandemic, Health Education England (HEE) mobilised a group of expert searchers from NHS libraries in England to develop a platform for librarians to share peer reviewed search strategies and results on the Knowledge for Healthcare website. Objectives: (1) To document the origins of the COVID-19 search bank, (2) evaluate attitudes of NHS librarians in England towards the search bank and (3) identify lessons learned and consider whether the initiative might be developed further. Methods: Structured interviews with the peer reviewers (n = 10) were conducted, and a questionnaire survey of the NHS library community using the search bank was undertaken. Results: The interviews confirmed the value of collaboration. Expert searchers worked in pairs to peer review submitted search strategies. The survey (85 responses) indicated that a majority had used the search bank, and approved of the project, with some differences of opinion on functionality and future developments. Discussion: Collaborative working for the search bank probably saved time for individual NHS librarians. The quality of the searches submitted was variable as were librarians' approaches to presentation and development of search strategies. Peer review benefits from a buddy approach among expert searchers and agreement about feedback provided to contributors. Conclusion: Search strategies are the most useful element of a search bank. Peer review can be challenging and would benefit from a formal structure, but it is professionally rewarding.
  • Non-invasive advanced respiratory support in end-of-life care and symptom management: systematic review

    Wenzel, David; Pepper, Coral (2022-10-13)
    Objectives: To narrate the canon of knowledge around symptom control at end of life for patients using, or having recently used, non-invasive advanced respiratory support (NARS) at end of life for respiratory failure. Methods: A systematic review forming a narrative synthesis from a wide range of sample papers from Medline, Embase, CINAHL, Emcare, Cochrane and OpenGrey databases. A secondary search of grey literature was also performed with hand searching reference lists and author citations. The review was undertaken using the ENTREQ checklist for quality. Results: In total, 22 studies were included in the synthesis and four themes were generated: NARS as a buoy (NARS can represent hope and relief from the symptoms of respiratory failure), NARS as an anchor (NARS brings significant treatment burden), Impact on Staff (uncertainty over the balance of benefit and burden as well as complex patient care drives distress among staff providing care) and the Process of Withdrawal (withdrawal of therapy felt to be futile exists as discrete event in patient care but is otherwise poorly defined). Conclusion: NARS represents a complex interplay of hope, symptom control, unnaturally prolonged death and treatment burden. The literature captures the breadth of these issues, but further, detailed, research is required in almost every aspect of practice around end-of-life care and NARS-especially how to manage symptoms at the end of life.
  • Elbow conditions: research priorities setting in partnership with the James Lind Alliance

    Singh, Harvinder; Chong, Han Hong; Raval, Parag; Divall, Pip; Pandey, Radhakant (2022-11-22)
    Objective: To undertake a UK-based James Lind Alliance (JLA) Priority Setting Partnership for elbow conditions and be representative of the views of patients, carers and healthcare professionals (HCPs). Setting: This was a national collaborative study organised through the British Elbow and Shoulder Society. Participants: Adult patients, carers and HCPs who have managed or experienced elbow conditions, their carers and HCPs in the UK involved in managing of elbow conditions. Methods: The rigorous JLA priority setting methodology was followed. Electronic and paper scoping surveys were distributed to identify potential research priority questions (RPQs). Initial responses were reviewed and a literature search was performed to cross-check categorised questions. Those questions already sufficiently answered were excluded and the remaining questions were ranked in a second survey according to priority for future elbow conditions research. Using the JLA methodology, responses from HCP and patients were combined to create a list of the top 18 questions. These were further reviewed in a dedicated multistakeholder workshop where the top 10 RPQs were agreed by consensus. Results: The process was completed over 24 months. The initial survey resulted in 467 questions from 165 respondents (73% HCPs and 27% patients/carers). These questions were reviewed and combined into 46 summary topics comprising: tendinopathy, distal biceps pathology, arthritis, stiffness, trauma, arthroplasty and cubital tunnel syndrome. The second (interim prioritisation) survey had 250 respondents (72% HCP and 28% patients/carers). The top 18 ranked questions from this survey were taken to the final workshop where a consensus was reached on the top 10 RPQs. Conclusions: The top 10 RPQs highlight areas of importance that currently lack sufficient evidence to guide diagnosis, treatment and rehabilitation of elbow conditions. This collaborative process will guide researchers and funders regarding the topics that should receive most future attention and benefit patients and HCPs.
  • Outcomes of unconstrained proximal interphalangeal joint arthroplasty: A systematic review

    Aujla, Randeep; Divall, Pip; Dias, Joseph (2022-03-31)
    Background: Unconstrained pyrocarbon and metal-on-polyethylene (MoP) proximal interphalangeal (PIP) joint arthroplasty is an increasingly popular alternative to silicone implants and arthrodesis. This systematic review appraises their outcomes. Methods: Thirty studies comprising 1,324 joints (813 pyrocarbon, 511 MoP) were included. Mean patient age was 59 years (38-78) and mean follow-up period was 54 months (12-118). Results: There were mean improvements of 4.5 points (2-6.9) in pain visual analogue score, 10.5° (-26 to 58) in range of motion (ROM), 3.1 kg (-4 to 7) in grip strength, 0.6 kg (-1.5 to 2) in pinch strength and 18 points (-3 to 29) in the disabilities of the arm, shoulder and hand score, with no significant differences between implant types. ROM gains deteriorated over time. Clinical complications were frequent (23%) and significantly more common with pyrocarbon, as were radiographic complications. However, most were mild-moderate and did not necessarily correlate with negative outcomes or dissatisfaction. Overall re-operation rate was 21%, and revision rate 11%, both more frequent with pyrocarbon. Most revisions were within 24 months, beyond which survival was maintained up to 10 years. Conclusions: Unconstrained PIP joint arthroplasty is effective in improving pain scores, active ROM, grip/pinch strength and patient-reported outcome measures, particularly in patients with osteoarthritis. Results are generally maintained at least to the medium term, although gains diminish in the longer term. Complication and early revision rates are high, particularly with pyrocarbon implants. Most patients express positive attitudes to arthroplasty, with significant improvements in patient-reported outcome measures for both pyrocarbon and MoP implants. Patients with post-traumatic and inflammatory arthropathy are generally less satisfied. There is currently insufficient data to recommend one implant type over another, although the early-to-medium term results of MoP implants are promising. Prospective surveillance via small joint registries is recommended. Level of Evidence: Level III (Therapeutic).
  • Frailty identification in the emergency department-a systematic review focussing on feasibility

    Elliott, Amy; Hull, Louise
    Introduction: risk-stratifying older people accessing urgent care is a potentially useful first step to ensuring that the most vulnerable are able to access optimal care from the start of the episode. While there are many risk-stratification tools reported in the literature, few have addressed the practical issues of implementation. This review sought evidence about the feasibility of risk stratification for older people with urgent care needs. Methods: medline was searched for papers addressing risk stratification and implementation (feasibility or evaluation or clinician acceptability). All search stages were conducted by two reviewers, and selected papers were graded for quality using the CASP tool for cohort studies. Data were summarised using descriptive statistics only. Results: about 1872 titles of potential interest were identified, of which 1827 were excluded on title/abstract review, and a further 43 after full-text review, leaving four papers for analysis. These papers described nine tools, which took between 1 and 10 minutes to complete for most participants. No more than 52% of potentially eligible older people were actually screened using any of the tools. Little detail was reported on the clinical acceptability of the tools tested. Discussion: the existing literature indicates that commonly used risk-stratification tools are relatively quick to use, but do not cover much more than 50% of the potential population eligible for screening in practice. Additional work is required to appreciate how tools are likely to be used, by whom, and when in order to ensure that they are acceptable to urgent care teams.
  • Frailty factors and outcomes in vascular surgery patients: a systematic review and meta-analysis

    Houghton, John; Nickinson, Andrew; Nduwayo, Sarah; Pepper, Coral; Rayt, Harjeet; Haunton, Victoria; Sayers, Robert
    Objective: To describe and critique tools used to assess frailty in vascular surgery patients, and investigate its associations with patient factors and outcomes. Background: Increasing evidence shows negative impacts of frailty on outcomes in surgical patients, but little investigation of its associations with patient factors has been undertaken. Methods: Systematic review and meta-analysis of studies reporting frailty in vascular surgery patients (PROSPERO registration: CRD42018116253) searching Medline, Embase, CINAHL, PsycINFO, and Scopus. Quality of studies was assessed using Newcastle-Ottawa scores (NOS) and quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria. Associations of frailty with patient factors were investigated by difference in means (MD) or expressed as risk ratios (RRs), and associations with outcomes expressed as odds ratios (ORs) or hazard ratios (HRs). Data were pooled using random-effects models. Results: Fifty-three studies were included in the review and only 8 (15%) were both good quality (NOS ≥ 7) and used a well-validated frailty measure. Eighteen studies (62,976 patients) provided data for the meta-analysis. Frailty was associated with increased age [MD 4.05 years; 95% confidence interval (CI) 3.35, 4.75], female sex (RR 1.32; 95% CI 1.14, 1.54), and lower body mass index (MD -1.81; 95% CI -2.94, -0.68). Frailty was associated with 30-day mortality [adjusted OR (AOR) 2.77; 95% CI 2.01-3.81), postoperative complications (AOR 2.16; 95% CI 1.55, 3.02), and long-term mortality (HR 1.85; 95% CI 1.31, 2.62). Sarcopenia was not associated with any outcomes. Conclusion: Frailty, but not sarcopenia, is associated with worse outcomes in vascular surgery patients. Well-validated frailty assessment tools should be preferred clinically, and in future research.
  • Change in V˙O 2peak in response to aerobic exercise training and the relationship with exercise prescription in people with COPD: A systematic review and meta-analysis

    Ward, Thomas J.C.; Jones, Amy V.; Trethewey, Ruth; Divall, Pip; Singh, Sally; Steiner, Michael; Evans, Rachael (2020-07)
    Background: Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (V˙O2peak) with aerobic training. Research question: The goal of this study was to investigate the effect of aerobic training and exercise prescription on V˙O2peak in COPD. Study design and methods: A systematic review was performed by using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases for all studies measuring V˙O2peak prior to and following supervised lower-limb aerobic training in COPD. A random effects meta-analysis limited to randomized controlled trials comparing aerobic training vs usual care was conducted. Other study designs were included in a secondary meta-analysis and meta-regression to investigate the influence of program and patient factors on outcome. Results: A total of 112 studies were included (participants, N = 3,484): 21 controlled trials (n = 489), of which 13 were randomized (n = 288) and 91 were uncontrolled (n = 2,995) studies. Meta-analysis found a moderate positive change in V˙O2peak (standardized mean difference, 0.52; 95% CI, 0.34-0.69) with the intervention. The change in V˙O2peak was positively associated with target duration of exercise session (P = .01) and, when studies > 1 year duration were excluded, greater total volume of exercise training (P = .01). Similarly, the change in V˙O2peak was greater for programs > 12 weeks compared with those 6 to 12 weeks when adjusted for age and sex. However, reported prescribed exercise intensity (P = .77), training modality (P > .35), and mode (P = .29) did not affect V˙O2peak. Cohorts with more severe airflow obstruction exhibited smaller improvements in V˙O2peak (P < .001). Interpretation: Overall, people with COPD achieved moderate improvements in V˙O2peak through supervised aerobic training. There is sufficient evidence to show that programs with greater total exercise volume, including duration of exercise session and program duration, are more effective. Reduced effects in severe disease suggest alternative aerobic training methods may be needed in this population.
  • Ethnicity and clinical outcomes in COVID-19: A systematic review and meta-analysis

    Sze, Shirley; Pan, Daniel; Martin, Christopher; Nazareth, Joshua; Minhas, Jatinder S; Divall, Pip; Pareek, Manish (2020-12)
    Background: Patients from ethnic minority groups are disproportionately affected by Coronavirus disease (COVID-19). We performed a systematic review and meta-analysis to explore the relationship between ethnicity and clinical outcomes in COVID-19. Methods: Databases (MEDLINE, EMBASE, PROSPERO, Cochrane library and MedRxiv) were searched up to 31st August 2020, for studies reporting COVID-19 data disaggregated by ethnicity. Outcomes were: risk of infection; intensive therapy unit (ITU) admission and death. PROSPERO ID: 180654. Findings: 18,728,893 patients from 50 studies were included; 26 were peer-reviewed; 42 were from the United States of America and 8 from the United Kingdom. Individuals from Black and Asian ethnicities had a higher risk of COVID-19 infection compared to White individuals. This was consistent in both the main analysis (pooled adjusted RR for Black: 2.02, 95% CI 1.67-2.44; pooled adjusted RR for Asian: 1.50, 95% CI 1.24-1.83) and sensitivity analyses examining peer-reviewed studies only (pooled adjusted RR for Black: 1.85, 95%CI: 1.46-2.35; pooled adjusted RR for Asian: 1.51, 95% CI 1.22-1.88). Individuals of Asian ethnicity may also be at higher risk of ITU admission (pooled adjusted RR 1.97 95% CI 1.34-2.89) (but no studies had yet been peer-reviewed) and death (pooled adjusted RR/HR 1.22 [0.99-1.50]). Interpretation: Individuals of Black and Asian ethnicity are at increased risk of COVID-19 infection compared to White individuals; Asians may be at higher risk of ITU admission and death. These findings are of critical public health importance in informing interventions to reduce morbidity and mortality amongst ethnic minority groups.
  • Non-surgical treatments for Morton's neuroma: A systematic review

    Thomson, Lauren; Divall, Pip; Bhatia, Maneesh (2020-10)
    Background: Morton's neuroma (MN) is an entrapment degenerative neuropathy with a strong predilection for the 3rd interdigital web space. The objective of our study was to identify the most significant evidence produced for the non-operative treatment of Morton's neuroma and assess outcomes of these interventions. Method: The electronic databases Medline, Ovid EMBASE, CINAHL and Cochrane CENTRAL from inception to October 2018 were searched. Two independent reviewers assessed the quality of the studies using the Modified Coleman Criteria. Statistics were combined across cohort studies to calculate pooled mean results, and improvements in outcomes. Results: Initial electronic and hand search identified 486 studies. After title and abstract review there were 38 that went on to full-text review. Finally, 22 studies were included in the final review. We identified 9 different non-operative treatment modalities; Corticosteroid injection, Alcohol injection, Extra-corporeal Shockwave therapy (ESWT), Radiofrequency Ablation (RFA), Cryoablation, Capsaicin injection, Botulinum toxin, Orthosis and YAG Laser Therapy. Corticosteroid showed a statistically significant reduction in mean VAS over all their studies (p < 0.01), with 50% success at 12 months. Alcohol showed promising short-term pain-relieving results only. Orthotics, Capsaicin injections, Cryoablation, Botulinum toxin, RFA and ESWT did show statistically significant improvements, but with limitation to their application. Conclusion: Following review, the authors would recommend the use of corticosteroid injections to treat Morton's neuromas. The authors feel that radio-frequency ablation and cryoablation would benefit from further well designed randomised controlled trials.
  • A systematic review of procedural outcomes in patients with proximal common carotid or innominate artery disease with or without tandem ipsilateral internal carotid artery disease

    Robertson, Vaux; Saratzis, Athanasios; Divall, Pip; Naylor, Ross (2020-12)
    Objective: To establish 30 day and mid term outcomes in patients treated for significant stenoses affecting the proximal common carotid artery (CCA) or innominate artery (IA) with/without tandem disease of the ipsilateral internal carotid artery (ICA). Methods: Systematic review of early and mid term outcomes in 1 969 patients from 77 studies (1960-2017) who underwent: (i) hybrid open retrograde angioplasty/stenting of the IA/proximal CCA plus carotid endarterectomy (CEA) in patients with tandem disease of the ipsilateral proximal ICA (n = 700); (ii) isolated open surgery to the IA or proximal CCA (no CEA) (n = 686); or (iii) an isolated endovascular approach to IA or proximal CCA stenoses (no CEA) (n = 583). Results: In the hybrid group with tandem disease (66% involving proximal CCA), the 30 day death/stroke was 3.3%, with a late ipsilateral stroke rate of 3.3% at a median six years follow up. Late re-stenosis was 10.5% for proximal CCA/IA and 4.1% for the ICA. In the isolated open surgery group (78% involving the IA), the 30 day death/stroke was 7%, with a late ipsilateral stroke rate of 1% at a median 12 years follow up. Late re-stenosis within aortic bypasses was 2.6%. In the isolated endovascular group (52% IA, 47% proximal CCA), the majority of procedures were done percutaneously (84%), with a 30 day death/stroke rate of 1.5%. Late ipsilateral stroke was 1% at a median four years follow up, with a re-stenosis rate of 9%. Conclusion: Procedural risks were higher following isolated open surgical interventions involving the proximal CCA/IA, compared with proximal lesions treated by isolated angioplasty/stenting, or in tandem with CEA. This higher morbidity/mortality may, however, reflect a greater proportion of innominate (vs. proximal CCA) lesions in open surgical series, changes in patient selection, time dependent evolution of medical interventions, and publication bias. The available data were limited and related to very different patient groups and management strategies spanning 57 years. Caution is raised, particularly for open surgery IA and CCA surgery, and for any procedures in asymptomatic patients. In symptomatic patients, the data cautiously support an "endovascular first" strategy for isolated proximal CCA/IA lesions and a hybrid approach for tandem proximal CCA/IA and ICA stenoses.

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