scholarly journals What is the clinical effectiveness and cost-effectiveness of conservative interventions for tendinopathy? An overview of systematic reviews of clinical effectiveness and systematic review of economic evaluations

2015 ◽  
Vol 19 (8) ◽  
pp. 1-134 ◽  
Author(s):  
Linda Long ◽  
Simon Briscoe ◽  
Chris Cooper ◽  
Chris Hyde ◽  
Louise Crathorne

BackgroundLateral elbow tendinopathy (LET) is a common complaint causing characteristic pain in the lateral elbow and upper forearm, and tenderness of the forearm extensor muscles. It is thought to be an overuse injury and can have a major impact on the patient’s social and professional life. The condition is challenging to treat and prone to recurrent episodes. The average duration of a typical episode ranges from 6 to 24 months, with most (89%) reporting recovery by 1 year.ObjectivesThis systematic review aims to summarise the evidence concerning the clinical effectiveness and cost-effectiveness of conservative interventions for LET.Data sourcesA comprehensive search was conducted from database inception to 2012 in a range of databases including MEDLINE, EMBASE and Cochrane Databases.Methods and outcomesWe conducted an overview of systematic reviews to summarise the current evidence concerning the clinical effectiveness and a systematic review for the cost-effectiveness of conservative interventions for LET. We identified additional randomised controlled trials (RCTs) that could contribute further evidence to existing systematic reviews. We searched MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Web of Science, The Cochrane Library and other important databases from inception to January 2013.ResultsA total of 29 systematic reviews published since 2003 matched our inclusion criteria. These were quality appraised using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist; five were considered high quality and evaluated using a Grading of Recommendations, Assessment, Development and Evaluation approach. A total of 36 RCTs were identified that were not included in a systematic review and 29 RCTs were identified that had only been evaluated in an included systematic review of intermediate/low quality. These were then mapped to existing systematic reviews where further evidence could provide updates. Two economic evaluations were identified.LimitationsThe summary of findings from the review was based only on high-quality evidence (scoring of > 5 AMSTAR). Other limitations were that identified RCTs were not quality appraised and dichotomous outcomes were also not considered. Economic evaluations took effectiveness estimates from trials that had small sample sizes leading to uncertainty surrounding the effect sizes reported. This, in turn, led to uncertainty of the reported cost-effectiveness and, as such, no robust recommendations could be made in this respect.ConclusionsClinical effectiveness evidence from the high-quality systematic reviews identified in this overview continues to suggest uncertainty as to the effectiveness of many conservative interventions for the treatment of LET. Although new RCT evidence has been identified with either placebo or active controls, there is uncertainty as to the size of effects reported within them because of the small sample size. Conclusions regarding cost-effectiveness are also unclear. We consider that, although updated or new systematic reviews may also be of value, the primary focus of future work should be on conducting large-scale, good-quality clinical trials using a core set of outcome measures (for defined time points) and appropriate follow-up. Subgroup analysis of existing RCT data may be beneficial to ascertain whether or not certain patient groups are more likely to respond to treatments.Study registrationThis study is registered as PROSPERO CRD42013003593.FundingThe National Institute for Health Research Health Technology Assessment programme.

2005 ◽  
Vol 21 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Gerry Richardson ◽  
Hugh Gravelle ◽  
Helen Weatherly ◽  
Gill Ritchie

Objectives: Interventions to support patient self-care of their condition aim to improve patient health and reduce health service costs. Consequently, they have attracted considerable policy interest. There is some evidence of clinical effectiveness but less attention has been paid to whether these interventions are cost-effective. This study examines the quality and quantity of existing evidence of the cost-effectiveness.Methods: A systematic review was carried out to assess the extent and quality of economic evaluations of self-care support interventions. Thirty-nine economic evaluations were assessed against a quality checklist developed to reflect the special features of these interventions.Results: The majority of the studies claimed that self-care support interventions were cost-effective or cost saving. The overall quality of economic evaluations was poor because of flaws in study designs, especially a narrow definition of relevant costs and short follow-up periods.Conclusions: The current evidence base does not support any general conclusion that self-care support interventions are cost-effective, but ongoing trials may provide clearer evidence.


2020 ◽  
Vol 24 (2) ◽  
pp. 1-180 ◽  
Author(s):  
Nigel Fleeman ◽  
Rachel Houten ◽  
Adrian Bagust ◽  
Marty Richardson ◽  
Sophie Beale ◽  
...  

Background Thyroid cancer is a rare cancer, accounting for only 1% of all malignancies in England and Wales. Differentiated thyroid cancer (DTC) accounts for ≈94% of all thyroid cancers. Patients with DTC often require treatment with radioactive iodine. Treatment for DTC that is refractory to radioactive iodine [radioactive iodine-refractory DTC (RR-DTC)] is often limited to best supportive care (BSC). Objectives We aimed to assess the clinical effectiveness and cost-effectiveness of lenvatinib (Lenvima®; Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar®; Bayer HealthCare, Leverkusen, Germany) for the treatment of patients with RR-DTC. Data sources EMBASE, MEDLINE, PubMed, The Cochrane Library and EconLit were searched (date range 1999 to 10 January 2017; searched on 10 January 2017). The bibliographies of retrieved citations were also examined. Review methods We searched for randomised controlled trials (RCTs), systematic reviews, prospective observational studies and economic evaluations of lenvatinib or sorafenib. In the absence of relevant economic evaluations, we constructed a de novo economic model to compare the cost-effectiveness of lenvatinib and sorafenib with that of BSC. Results Two RCTs were identified: SELECT (Study of [E7080] LEnvatinib in 131I-refractory differentiated Cancer of the Thyroid) and DECISION (StuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine-refractory thyrOid caNcer). Lenvatinib and sorafenib were both reported to improve median progression-free survival (PFS) compared with placebo: 18.3 months (lenvatinib) vs. 3.6 months (placebo) and 10.8 months (sorafenib) vs. 5.8 months (placebo). Patient crossover was high (≥ 75%) in both trials, confounding estimates of overall survival (OS). Using OS data adjusted for crossover, trial authors reported a statistically significant improvement in OS for patients treated with lenvatinib compared with those given placebo (SELECT) but not for patients treated with sorafenib compared with those given placebo (DECISION). Both lenvatinib and sorafenib increased the incidence of adverse events (AEs), and dose reductions were required (for > 60% of patients). The results from nine prospective observational studies and 13 systematic reviews of lenvatinib or sorafenib were broadly comparable to those from the RCTs. Health-related quality-of-life (HRQoL) data were collected only in DECISION. We considered the feasibility of comparing lenvatinib with sorafenib via an indirect comparison but concluded that this would not be appropriate because of differences in trial and participant characteristics, risk profiles of the participants in the placebo arms and because the proportional hazard assumption was violated for five of the six survival outcomes available from the trials. In the base-case economic analysis, using list prices only, the cost-effectiveness comparison of lenvatinib versus BSC yields an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £65,872, and the comparison of sorafenib versus BSC yields an ICER of £85,644 per QALY gained. The deterministic sensitivity analyses show that none of the variations lowered the base-case ICERs to < £50,000 per QALY gained. Limitations We consider that it is not possible to compare the clinical effectiveness or cost-effectiveness of lenvatinib and sorafenib. Conclusions Compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. Both treatments exhibit estimated ICERs of > £50,000 per QALY gained. Further research should include examination of the effects of lenvatinib, sorafenib and BSC (including HRQoL) for both symptomatic and asymptomatic patients, and the positioning of treatments in the treatment pathway. Study registration This study is registered as PROSPERO CRD42017055516. Funding The National Institute for Health Research Health Technology Assessment programme.


Author(s):  
Claudia Pieper ◽  
Sarah Schröer ◽  
Anna-Lisa Eilerts

Work environment factors are highly correlated with employees’ health and well-being. Our aim was to sum up current evidence of health promotion interventions in the workplace, focusing on interventions for the prevention of musculoskeletal disorders, psychological and behavioral disorders as well as interventions for older employees and economic evaluations. We conducted a comprehensive literature search including systematic reviews published from April 2012 to October 2017 in electronic databases and search engines, websites of relevant organizations and institutions. It consisted of simple and specific terms and word combinations related to workplace health promotion based on the search strategy of a previous review. After full-text screening, 74 references met the eligibility criteria. Using the same search strategy, there was a higher proportion of relevant high-quality studies as compared with the earlier review. The heterogeneity of health promotion interventions regarding intervention components, settings and study populations still limits the comparability of studies. Future studies should also address the societal and insurer perspective, including costs to the worker such as lost income and lost time at work of family members due to caregiving activities. To this end, more high-quality evidence is needed.


2014 ◽  
Vol 2 (21) ◽  
pp. 1-118 ◽  
Author(s):  
Fiona Paton ◽  
Duncan Chambers ◽  
Paul Wilson ◽  
Alison Eastwood ◽  
Dawn Craig ◽  
...  

BackgroundThere has been growing interest in the NHS over recent years in the use of enhanced recovery programmes for elective surgery to deliver productivity gains through reduced length of stay, fewer postoperative complications, reduced readmissions and improved patient outcomes.ObjectivesTo evaluate the clinical effectiveness and cost-effectiveness of enhanced recovery programmes for patients undergoing elective surgery in acute hospital settings. To identify and critically describe key factors associated with successful adoption, implementation and sustainability of enhanced recovery programmes in UK settings. To summarise existing knowledge about patient experience of enhanced recovery programmes in UK settings.Data sourcesEight databases, including Database of Abstracts of Reviews and Effects, International Prospective of Systematic Reviews, NHS Economic Evaluation Database and MEDLINE, were searched from 1990 to March 2013 without language restrictions. Relevant reports and guidelines and reference lists of retrieved articles were scanned to identify additional studies.Review methodsSystematic reviews, randomised controlled trials (RCTs), economic evaluations, and UK NHS cost analysis studies were included if they evaluated the impact of enhanced recovery programmes on any health- and cost-related outcomes. Eligible studies included patients undergoing elective surgery in an acute hospital setting. Implementation case studies and surveys of patient experience in a UK setting were also eligible for inclusion. Quality assessment of systematic reviews, RCTs and economic evaluations was based on existing Centre for Reviews and Dissemination processes. All stages of the review process were performed by one researcher and checked by a second with discrepancies resolved by consensus. The type and range of evidence precluded meta-analysis and we therefore performed a narrative synthesis, differentiating between clinical effectiveness and cost-effectiveness, implementation case studies and evidence on patient experience.ResultsSeventeen systematic reviews of varying quality were included in this report. Twelve additional RCTs were included; all were considered at high risk of bias. Most of the evidence focused on colorectal surgery. Fourteen innovation case studies and 15 implementation case studies undertaken in NHS settings were identified and provide descriptions of factors critical to the success of an enhanced recovery programme. Ten relevant economic evaluations were identified evaluating costs and outcomes over short time horizons. Despite the plethora of studies, robust evidence was sparse. Evidence for colorectal surgery suggests that enhanced recovery programmes may reduce hospital stays by 0.5–3.5 days compared with conventional care. There were no significant differences in reported readmission rates. Other surgical specialties showed greater variation in reported reductions in length of stay reflecting the limited evidence identified.LimitationsFindings relating to other clinical outcomes, cost-effectiveness, implementation and patient experience were hampered by a lack of robust evidence and poor reporting.ConclusionsThere is consistent, albeit limited, evidence that enhanced recovery programmes may reduce length of patient hospital stay without increasing readmission rates. The extent to which managers and clinicians considering implementing enhanced recovery programmes can realise reductions and cost savings will depend on length of stays achieved under their existing care pathway. RCTs comparing an enhanced recovery programme with conventional care continue to be conducted and published. Further single-centre RCTs of this kind are not a priority. Rather, what is needed is improved collection and reporting of how enhanced recovery programmes are implemented, resourced and experienced in NHS settings.FundingThe National Institute for Health Research Health Services and Delivery Research programme.


2020 ◽  
Vol 3 ◽  
pp. 83
Author(s):  
Eileen Mitchell ◽  
Elayne Ahern ◽  
Sanjib Saha ◽  
Dominic Trepel

Background: New emerging evidence has demonstrated the need for effective interventions to help people living with an acquired brain injury (ABI). Evidence on cost-effectiveness, which can help inform use of limited resources, is scarce in this area and therefore the purpose of this systematic review is to critically appraise and consolidate the current evidence on economic evaluations of ABI rehabilitation interventions. Methods: Systematic review methodology will be applied to identify, select and extract data from published economic evaluation studies (trial-based, non-trial based, simulation-based, decision model and trial-based model economic evaluations) of ABI treatment interventions in adults. A systematic literature search will be conducted on the following electronic databases: EMBASE, Econlit, CINAHL, Medline, Econlit, the National Health Service Economic Evaluation Database and PsyclNFO. This review will only include cost-effectiveness analysis studies (e.g., cost per life year gained), cost-benefit and cost minimisation analyses in which the designs were randomised controlled trials (RCTs), non-RCT studies, cost-utility analyses (e.g., cost per quality-adjusted life year (QALY) gained or cost per disability-adjusted life year averted), cohort studies, and modeling studies. Only studies that were published in English, associated with adults who have an ABI will be included. There will be no restrictions on perspective, sample size, country, follow-up duration or setting. The search strategy terms will include the following: acquired brain injury, brain*; cost*; or cost–benefit analysis*. Following data extraction, a narrative summary and tables will be used to summarize the characteristics and results of included studies. Discussion: The findings from this review will be beneficial to health policy decision makers when examining the evidence of economic evaluations in this field. In addition, it is anticipated that this review will identify gaps in the current economic literature to inform future-related research. Systematic review registration: PROSPERO CRD42020187469 (25th June 2020).


2020 ◽  
Vol 7 (1) ◽  
pp. 5
Author(s):  
Jack Nunn ◽  
Steven Chang

Systematic reviews are a type of review that uses repeatable analytical methods to collect secondary data and analyse it. Systematic reviews are a type of evidence synthesis which formulate research questions that are broad or narrow in scope, and identify and synthesize data that directly relate to the systematic review question. While some people might associate ‘systematic review’ with 'meta-analysis', there are multiple kinds of review which can be defined as ‘systematic’ which do not involve a meta-analysis. Some systematic reviews critically appraise research studies, and synthesize findings qualitatively or quantitatively. Systematic reviews are often designed to provide an exhaustive summary of current evidence relevant to a research question. For example, systematic reviews of randomized controlled trials are an important way of informing evidence-based medicine, and a review of existing studies is often quicker and cheaper than embarking on a new study. While systematic reviews are often applied in the biomedical or healthcare context, they can be used in other areas where an assessment of a precisely defined subject would be helpful. Systematic reviews may examine clinical tests, public health interventions, environmental interventions, social interventions, adverse effects, qualitative evidence syntheses, methodological reviews, policy reviews, and economic evaluations. An understanding of systematic reviews and how to implement them in practice is highly recommended for professionals involved in the delivery of health care, public health and public policy.


2016 ◽  
Vol 20 (46) ◽  
pp. 1-246 ◽  
Author(s):  
Matt Stevenson ◽  
Abdullah Pandor ◽  
Marrissa Martyn-St James ◽  
Rachid Rafia ◽  
Lesley Uttley ◽  
...  

BackgroundSepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity.ObjectivesTo determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE®(Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTestTM(Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-of-flight mass spectrometry).Data sourcesThirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles.Review methodsA systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty.ResultsFor the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based.LimitationsRobust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable.ConclusionsThe clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required.Study registrationThis study is registered as PROSPERO CRD42015016724.FundingThe National Institute for Health Research Health Technology Assessment programme.


2015 ◽  
Vol 19 (20) ◽  
pp. 1-336 ◽  
Author(s):  
Emma Loveman ◽  
Vicky R Copley ◽  
Jill Colquitt ◽  
David A Scott ◽  
Andy Clegg ◽  
...  

BackgroundIdiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough, and as the disease progresses there is a considerable impact on day-to-day life. Few treatments are currently available.ObjectivesTo conduct a systematic review of clinical effectiveness and an analysis of cost-effectiveness of treatments for IPF based on an economic model informed by systematic reviews of cost-effectiveness and quality of life.Data sourcesEleven electronic bibliographic databases, including MEDLINE, EMBASE, Web of Science, and The Cochrane Library and the Centre for Reviews and Dissemination databases, were searched from database inception to July 2013. Reference lists of relevant publications were also checked and experts consulted.MethodsTwo reviewers independently screened references for the systematic reviews, extracted and checked data from the included studies and appraised their risk of bias. An advisory group was consulted about the choice of interventions until consensus was reached about eligibility. A narrative review with meta-analysis was undertaken, and a network meta-analysis (NMA) was performed. A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Parameter values were obtained from NMA and systematic reviews. Univariate and probabilistic sensitivity analyses were undertaken. The model perspective is NHS and Personal Social Services, and discount rate is 3.5% for costs and health benefits.ResultsFourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, threeN-acetylcysteine (NAC) (alone or in combination), four pirfenidone, one BIBF 1120, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good, with a low risk of bias. The current evidence suggests that some treatments appear to be clinically effective. The model base-case results show increased survival for five pharmacological treatments, compared with best supportive care, at increased cost. General recommendations cannot be made of their cost-effectiveness owing to limitations in the evidence base.LimitationsFew direct comparisons of treatments were identified. An indirect comparison through a NMA was performed; however, caution is recommended in the interpretation of these results. In relation to the economic model, there is an assumption that pharmacological treatments have a constant effect on the relative rate of per cent predicted forced vital capacity decline.ConclusionsFew interventions have any statistically significant effect on IPF and a lack of studies on palliative care approaches was identified. Research is required into the effects of symptom control interventions, in particular pulmonary rehabilitation and thalidomide. Other research priorities include a well-conducted randomised controlled trial on inhaled NAC therapy and an updated evidence synthesis once the results of ongoing studies are reported.Study registrationThis study is registered as PROSPERO CRD42012002116.FundingThe National Institute for Health Research Health Technology Assessment programme.


2019 ◽  
Author(s):  
Saja Almazrou ◽  
Rachel A Elliott ◽  
Roger D Knaggs ◽  
Shiekha S AlAujan

Abstract Background To summarize and critically appraise the current evidence for the cost effectiveness of pain management services for managing chronic back pain. Methods Electronic searches were conducted in MEDLINE, EMBASE and PsycINFO from their inception to February 2019. Full economic evaluations undertaken from any perspective conducted alongside randomized clinical trials (RCTs) or based on decision analysis models were included. Cochrane Back Review Group (CBRG) risk assessment and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist were used to assess the methodological quality of eligible studies. Results Five studies fulfilled eligibility criteria. The interventions varied significantly between studies in terms of the number and types? of treatment modalities, intensity and the duration of the program. Interventions were compared with either standard care, which varied according to the country and the setting; or to surgical interventions. Three studies showed that pain management services are cost effective, while two studies showed that these services are not cost effective. In this review, three out of five studies had a high risk of bias based on the design of the randomised controlled trials (RCTs). In addition, there were limitations in the statistical and sensitivity analyses in the economic evaluations. Therefore, the results from these studies need to be interpreted with caution. Conclusion Pain management services may be cost effective for the management of low back pain. However, this systematic review highlights the variability of evidence supporting pain management services for patients with back pain. This is due to the variability of the interventions, comparators and outcomes.


2019 ◽  
Vol 6 (12) ◽  
Author(s):  
Jason P Burnham ◽  
Stephanie A Fritz ◽  
Lauren H Yaeger ◽  
Graham A Colditz

Abstract Background Telemedicine use is increasing in many specialties, but its impact on clinical outcomes in infectious diseases has not been systematically reviewed. We reviewed the current evidence for clinical effectiveness of telemedicine infectious diseases consultations, including outcomes of mortality, hospital readmission, antimicrobial use, cost, length of stay, adherence, and patient satisfaction. Methods We queried Ovid MEDLINE 1946-, Embase.com 1947-, Scopus 1823-, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov 1997- through August 5, 2019, for studies looking at clinical outcomes of infectious diseases in the setting of telemedicine use. We did not restrict by language or year of publication. Clinical outcomes searched included 30-day all-cause mortality, 30-day readmissions, patient compliance/adherence, patient satisfaction, cost or cost-effectiveness, length of hospital stay, antimicrobial use, and antimicrobial stewardship. Bias was assessed using standard methodologies. PROSPERO CRD42018105225. Results From a search pool of 1154 studies, only 18 involved telemedicine infectious diseases consultation and our selected clinical outcomes. The outcomes tracked were heterogeneous, precluding meta-analysis, and the majority of studies were of poor quality. Overall, clinical outcomes with telemedicine infectious diseases consultation seem comparable to in-person infectious diseases consultation. Conclusions Although in widespread use, the clinical effectiveness of telemedicine infectious diseases consultations has yet to be sufficiently studied. Further studies, or publication of previously collected and available data, are warranted to verify the cost-effectiveness of this widespread practice. Systematic review registration PROSPERO CRD42018105225.


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