BACKGROUND: Search filters are standardised sets of search terms, with validated performance, that are designed to retrieve studies with specific characteristics. A cost-utility analysis (CUA) is the preferred type of economic evaluation to underpin decision-making at the National Institute for Health and Care Excellence (NICE). Until now, when searching for economic evidence for NICE guidelines, we have used a broad set of health economic-related search terms, even when the reviewer's interest is confined to CUAs alone.
METHODS: We developed search filters to retrieve CUAs from MEDLINE and Embase. Our aim was to achieve recall of 90% or better across both databases while reducing the overall yield compared with our existing broad economic filter. We used the relative recall method along with topic expert input to derive and validate 3 pairs of filters, assessed by their ability to identify a gold-standard set of CUAs that had been used in published NICE guidelines. We developed and validated MEDLINE and Embase filters in pairs (testing whether, when used together, they find target studies in at least 1 database), as this is how they are used in practice. We examined the proxy-precision of our new filters by comparing their overall yield with our previous approach using publications indexed in a randomly selected year (2010).
RESULTS: All 3 filter-pairs exceeded our target recall and led to substantial improvements in search proxy-precision. Our paired 'sensitive' filters achieved 100% recall (95% CI 99.0 to 100%) in the validation set. Our paired 'precise' filters also had very good recall (97.6% [95%CI: 95.4 to 98.9%]). We estimate that, compared with our previous search strategy, using the paired 'sensitive' filters would reduce reviewer screening burden by a factor of 5 and the 'precise' versions would do so by a factor of more than 20.
CONCLUSIONS: Each of the 3 paired cost-utility filters enable the identification of almost all CUAs from MEDLINE and Embase from the validation set, with substantial savings in screening workload compared to our previous search practice. We would encourage other researchers who regularly use multiple databases to consider validating search filters in combination as this will better reflect how they use databases in their everyday work.
BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) and the associated risk of stroke are emerging epidemics throughout the world. Suboptimal use of oral anticoagulants for stroke prevention has been widely reported from observational studies. In recent years, direct oral anticoagulants (DOACs) have been introduced for thromboprophylaxis. We conducted a systematic literature review to evaluate current practices of anticoagulation in AF, pharmacologic features and adoption patterns of DOACs, their impacts on proportion of eligible patients with AF who receive oral anticoagulants, persisting challenges and future prospects for optimal anticoagulation.
LITERATURE SOURCE AND SELECTION CRITERIA: In conducting this review, we considered the results of relevant prospective and retrospective observational studies from real-world practice settings. PubMed (MEDLINE), Scopus (RIS), Google Scholar, EMBASE and Web of Science were used to source relevant literature. There were no date limitations, while language was limited to English. Selection was limited to articles from peer reviewed journals and related to our topic.
RESULTS: Most studies identified in this review indicated suboptimal use of anticoagulants is a persisting challenge despite the availability of DOACs. Underuse of oral anticoagulants is apparent particularly in patients with a high risk of stroke. DOAC adoption trends are quite variable, with slow integration into clinical practice reported in most countries; there has been limited impact to date on prescribing practice.
CONCLUSION: Available data from clinical practice suggest that suboptimal oral anticoagulant use in patients with AF and poor compliance with guidelines still remain commonplace despite transition to a new era of anticoagulation featuring DOACs.
Since 2008, the direct-acting oral anticoagulants (DOACs) have expanded the therapeutic options of cardiovascular diseases with recognized clinical and epidemiological impact, such as non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE), and also in the preventive setting of orthopedic surgical patients. The large body of evidence, not only from pivotal clinical trials but also from ‘real-world’ postmarketing observational findings (e.g. analytical epidemiological studies and registry data) gathered to date allow for a first attempt at verifying a posteriori whether or not the pharmacological advantages of the DOACs actually translate into therapeutic innovation, with relevant implications for clinicians, regulators and patients. This review aims to synthesize the risk–benefit profile of DOACs in the aforementioned consolidated indications through an ‘evidence summary’ approach gathering the existent evidence-based data, particularly systematic reviews with meta-analyses of randomized controlled trials, as well as observational studies, comparing DOACs with vitamin K antagonists. Clinical evidence will be discussed and compared with major international guidelines to identify whether an update is needed. Controversial clinically relevant safety issues will be also examined in order to highlight current challenges and unsettled questions (e.g. actual bleeding risk in susceptible populations). It is anticipated that the large number of publications on NVAF or VTE (44 systematic reviews with meta-analyses and 12 observational studies retained in our analysis) suggests the potential existence of overlapping studies and calls for common criteria to qualitatively and quantitatively assess discordances, thus guiding future research.
OBJECTIVE: To determine the comparative effectiveness of exercise versus drug interventions on mortality outcomes.
DESIGN: Metaepidemiological study.
ELIGIBILITY CRITERIA: Meta-analyses of randomised controlled trials with mortality outcomes comparing the effectiveness of exercise and drug interventions with each other or with control (placebo or usual care).
DATA SOURCES: Medline and Cochrane Database of Systematic Reviews, May 2013.
MAIN OUTCOME MEASURE: Mortality.
DATA SYNTHESIS: We combined study level death outcomes from exercise and drug trials using random effects network meta-analysis.
RESULTS: We included 16 (four exercise and 12 drug) meta-analyses. Incorporating an additional three recent exercise trials, our review collectively included 305 randomised controlled trials with 339,274 participants. Across all four conditions with evidence on the effectiveness of exercise on mortality outcomes (secondary prevention of coronary heart disease, rehabilitation of stroke, treatment of heart failure, prevention of diabetes), 14,716 participants were randomised to physical activity interventions in 57 trials. No statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes. Physical activity interventions were more effective than drug treatment among patients with stroke (odds ratios, exercise v anticoagulants 0.09, 95% credible intervals 0.01 to 0.70 and exercise v antiplatelets 0.10, 0.01 to 0.62). Diuretics were more effective than exercise in heart failure (exercise v diuretics 4.11, 1.17 to 24.76). Inconsistency between direct and indirect comparisons was not significant.
CONCLUSIONS: Although limited in quantity, existing randomised trial evidence on exercise interventions suggests that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.
OBJECTIFS: En raison d'un risque élevé de thromboembolie chez les patients subissant une chirurgie orthopédique majeure, il est devenu pratique courante de donner un traitement thromboembolique. Nous avons évalué l'efficacité relative et la rentabilité de deux nouveaux anticoagulants oraux, le rivaroxaban et le dabigatran, par rapport à l'énoxaparine sous-cutanée pour la prévention de la thromboembolie après remplacement total de la hanche (PTH) et la chirurgie de remplacement total du genou (PTG).
MÉTHODES: Nous avons effectué une revue systématique de la littérature pour évaluer l'efficacité et la sécurité, et la qualité de la documentation évaluée en utilisant GRADE. Rapport coût-efficacité a été évaluée par l'élaboration d'un modèle de décision. Le modèle combiné deux modules; un arbre de décision pour la prophylaxie à court terme et un modèle de Markov pour les complications à long terme et le gain de survie.
RÉSULTATS: Pour rivaroxaban par rapport à l'énoxaparine, nous avons constaté une diminution statistiquement significative de la thrombose veineuse profonde, mais aussi une tendance à l'augmentation du risque de saignement majeur. Pour la mortalité et l'embolie pulmonaire, il n'y avait pas de différences statistiquement significatives entre les traitements. On n'a pas trouvé de différences statistiquement significatives entre le dabigatran et l'énoxaparine pour nos efficacité et de sécurité des résultats. En supposant une volonté de payer des EUR62,500 par QALY, rivaroxaban après PTH avait une probabilité de 38 pour cent, et l'énoxaparine suivante TKR avait une probabilité de 34 pour cent d'être rentable. L'efficacité clinique a eu le plus grand impact sur la prise de l'incertitude.
CONCLUSIONS: dabigatran et rivaroxaban sont comparables à l'énoxaparine après PTH et PTG concernant l'efficacité et la sécurité des résultats. Cependant, il existe une grande incertitude quant à quelle stratégie est rentable, le plus. Plus de recherche sur l'efficacité clinique du rivaroxaban et le dabigatran est susceptible de changer nos résultats.
BACKGROUND: Pharmacologic thromboprophylaxis reduces the risk for venous thromboembolism after total hip replacement (THR) or total knee replacement (TKR). New oral anticoagulants (NOACs), including direct thrombin inhibitors and factor Xa inhibitors, are emerging options for thromboprophylaxis after these procedures.
PURPOSE: To compare the benefits and risks of NOACs versus standard thromboprophylaxis for adults having THR or TKR.
DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2009 through March 2013.
STUDY SELECTION: English-language systematic reviews.
DATA EXTRACTION: Two independent reviewers abstracted data and rated study quality and strength of evidence.
DATA SYNTHESIS: Six good-quality systematic reviews compared NOACs with low-molecular-weight heparin (LMWH) for thromboprophylaxis after THR or TKR. Risk for symptomatic deep venous thrombosis, but not risk for death or nonfatal pulmonary embolism, was reduced with factor Xa inhibitors compared with LMWH (4 fewer events per 1000 patients). Conversely, the risk for major bleeding increased (2 more events per 1000 patients). Outcomes of dabigatran did not significantly differ from those of LMWH. Indirect evaluation of NOACs by common comparison with LMWH showed nonsignificantly reduced risks for venous thromboembolism with rivaroxaban compared with dabigatran (risk ratio [RR], 0.68 [95% CI, 0.21 to 2.23]) and apixaban (RR, 0.59 [CI, 0.26 to 1.33]) but increased major bleeding. New oral anticoagulants have not been compared with warfarin, aspirin, or unfractionated heparin.
LIMITATIONS: Head-to-head comparisons among NOACs were not available. Efficacy is uncertain in routine clinical practice.
CONCLUSION: New oral anticoagulants are effective for thromboprophylaxis after THR and TKR. Their clinical benefits over LMWH are marginal and offset by increased risk for major bleeding.
PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.
CONTEXTE: L'utilisation du traitement anticoagulant pendant la grossesse est difficile en raison du risque de complications à la fois mère ou le foetus. Cette directive se concentre sur la gestion de la TEV et thrombophilie ainsi que l'utilisation d'agents anti-thrombotiques pendant la grossesse.
Méthodes: Les méthodes de cette directive suivre la méthodologie pour le développement de la thérapie antithrombotique et la prévention des lignes directrices de la thrombose: Traitement antithrombotique et la prévention de la thrombose, 9ème édition: American College of Physicians lignes directrices de la poitrine de Evidence-Based Clinical Practice dans ce supplément.
RÉSULTATS: Nous recommandons héparine de bas poids moléculaire pour la prévention et le traitement de la TEV chez les femmes enceintes au lieu de l'héparine non fractionnée (Grade 1B). Pour les femmes enceintes atteintes de la TEV aiguë, nous suggérons que les anticoagulants être poursuivi pendant au moins 6 semaines après l'accouchement (pour une durée minimum d'un traitement de 3 mois) par rapport aux durées plus courtes de traitement (Niveau 2C). Pour les femmes qui remplissent les critères de laboratoire pour les anticorps (APLA) syndrome des antiphospholipides et répondent aux critères de l'APLA cliniques basés sur une histoire de trois ou plus des pertes de la grossesse, il est recommandé administration avant l'accouchement de l'héparine non fractionnée prophylactique ou intermédiaire-dose ou prophylactique bas poids moléculaire héparine associée à l'aspirine à faible dose (75-100 mg / j) pendant l'absence de traitement (Grade 1B). Pour les femmes avec thrombophilie héréditaire et une histoire de complications de la grossesse, il est conseillé de ne pas utiliser une prophylaxie anti-thrombotique (Grade 2C). Pour les femmes ayant deux ou plusieurs fausses couches mais sans APLA ou thrombophilie, nous déconseillons la prophylaxie antithrombotique (Grade 1B).
CONCLUSIONS: La plupart des recommandations contenues dans ce guide sont basées sur des études observationnelles et l'extrapolation à partir d'autres populations. Il ya un besoin urgent d'études bien conçues dans cette population.
BACKGROUND: This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies.
METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.
RESULTS: We present 23 recommendations for pertinent clinical questions. For primary prevention of cardiovascular disease, we suggest low-dose aspirin (75-100 mg/d) in patients aged > 50 years over no aspirin therapy (Grade 2B). For patients with established coronary artery disease, defined as patients 1-year post-acute coronary syndrome, with prior revascularization, coronary stenoses > 50% by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing, we recommend long-term low-dose aspirin or clopidogrel (75 mg/d) (Grade 1A). For patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI) with stent placement, we recommend for the first year dual antiplatelet therapy with low-dose aspirin in combination with ticagrelor 90 mg bid, clopidogrel 75 mg/d, or prasugrel 10 mg/d over single antiplatelet therapy (Grade 1B). For patients undergoing elective PCI with stent placement, we recommend aspirin (75-325 mg/d) and clopidogrel for a minimum duration of 1 month (bare-metal stents) or 3 to 6 months (drug-eluting stents) (Grade 1A). We suggest continuing low-dose aspirin plus clopidogrel for 12 months for all stents (Grade 2C). Thereafter, we recommend single antiplatelet therapy over continuation of dual antiplatelet therapy (Grade 1B).
CONCLUSIONS: Recommendations continue to favor single antiplatelet therapy for patients with established coronary artery disease. For patients with acute coronary syndromes or undergoing elective PCI with stent placement, dual antiplatelet therapy for up to 1 year is warranted.
Norwegian Knowledge Centre for the Health Services has on request from Lovisenberg Diakonale Hospital reviewed the scientific evidence on the effect of graduated compression stockings (GCS) for prevention of deep vein thrombosis (DVT) among surgical and medical patients in hospitals.
Systematic literature search was carried out in relevant medical databases. We included tree systematic reviews. The systematic reviews had moderately to high methodological quality.
The evidence indicates that GCS prevents the formation of DVT among surgical patients, both alone and on a background of other prophylactic methods. It seems that knee length GCS is as effective in prevention of DVT as thigh length GCS. The evidence of GCS for prevention of DVT is less conclusive regarding medical patients.
Use of GCS also prevents development of post thrombotic syndrome, i.e. a condition that can occur after DVT.
Further research is necessary to identify which compression graduate is more effective and duration of time that GCS should be worn to prevent DVT.
Search filters are standardised sets of search terms, with validated performance, that are designed to retrieve studies with specific characteristics. A cost-utility analysis (CUA) is the preferred type of economic evaluation to underpin decision-making at the National Institute for Health and Care Excellence (NICE). Until now, when searching for economic evidence for NICE guidelines, we have used a broad set of health economic-related search terms, even when the reviewer's interest is confined to CUAs alone.
METHODS:
We developed search filters to retrieve CUAs from MEDLINE and Embase. Our aim was to achieve recall of 90% or better across both databases while reducing the overall yield compared with our existing broad economic filter. We used the relative recall method along with topic expert input to derive and validate 3 pairs of filters, assessed by their ability to identify a gold-standard set of CUAs that had been used in published NICE guidelines. We developed and validated MEDLINE and Embase filters in pairs (testing whether, when used together, they find target studies in at least 1 database), as this is how they are used in practice. We examined the proxy-precision of our new filters by comparing their overall yield with our previous approach using publications indexed in a randomly selected year (2010).
RESULTS:
All 3 filter-pairs exceeded our target recall and led to substantial improvements in search proxy-precision. Our paired 'sensitive' filters achieved 100% recall (95% CI 99.0 to 100%) in the validation set. Our paired 'precise' filters also had very good recall (97.6% [95%CI: 95.4 to 98.9%]). We estimate that, compared with our previous search strategy, using the paired 'sensitive' filters would reduce reviewer screening burden by a factor of 5 and the 'precise' versions would do so by a factor of more than 20.
CONCLUSIONS:
Each of the 3 paired cost-utility filters enable the identification of almost all CUAs from MEDLINE and Embase from the validation set, with substantial savings in screening workload compared to our previous search practice. We would encourage other researchers who regularly use multiple databases to consider validating search filters in combination as this will better reflect how they use databases in their everyday work.
