Protocol for a systematic review of prognostic models for the recurrence of venous thromboembolism (VTE) following treatment for a first unprovoked VTE

BACKGROUND: Venous thromboembolism (VTE) is a chronic disease, with fatal recurrences occurring in 5% to 9% of patients, yet it is also one of the best examples of preventable disease. Prognostic models that utilise multiple prognostic factors (demographic, clinical and laboratory patient characteristics) in combination to predict individual outcome risk may allow the identification of patients who would benefit from long-term anticoagulation therapy, and conversely those that would benefit from stopping such therapy due to a low risk of recurrence. The study will systematically review the evidence on potential prognostic models for the recurrence of VTE or adverse outcomes following the cessation of therapy, and synthesise and summarise each model’s prognostic value. The review has been registered with PROSPERO (CRD42013003494). METHODS/DESIGN: Articles will be sought from the Cochrane library (CENTRAL, CDSR, DARE, HTA databases), MEDLINE and EMBASE. Trial registers will be searched for ongoing studies, and conference abstracts will be sought. Reference lists and subject experts will be utilised. No restrictions on language of publications will be applied. Studies of any design will be included if they examine, in patients ceasing therapy after at least three months’ treatment with an oral anticoagulant therapy, whether more than one factor in combination is associated with the risk of VTE recurrence or another adverse outcome. Study quality will be assessed using appropriate guidelines for prognostic models. Prognostic models will be summarised qualitatively and, if tested in multiple validation studies, their predictive performance will be summarised using a random-effects meta-analysis model to account for any between-study heterogeneity. DISCUSSION: The results of the review will identify prognostic models for the risk of VTE recurrence or adverse outcome following cessation of therapy for a first unprovoked VTE. These will be informative for clinicians currently treating patients for a first unprovoked VTE and considering whether to stop treatment or not for particular individuals. The conclusions of the review will also inform the potential development of new prognostic models and clinical prediction rules to identify those at high or low risk of VTE recurrence or adverse outcome following a first unprovoked VTE

Climate Change Meets the Law of the Horse

The climate change policy debate has only recently turned its full attention to adaptation - how to address the impacts of climate change we have already begun to experience and that will likely increase over time. Legal scholars have in turn begun to explore how the many different fields of law will and should respond. During this nascent period, one overarching question has gone unexamined: how will the legal system as a whole organize around climate change adaptation? Will a new distinct field of climate change adaptation law and policy emerge, or will legal institutions simply work away at the problem through unrelated, duly self-contained fields, as in the famous Law of the Horse? This Article is the first to examine that question comprehensively, to move beyond thinking about the law and climate change adaptation to consider the law of climate change adaptation. Part I of the Article lays out our methodological premises and approach. Using a model we call Stationarity Assessment, Part I explores how legal fields are structured and sustained based on assumptions about the variability of natural, social, and economic conditions, and how disruptions to that regime of variability can lead to the emergence of new fields of law and policy. Case studies of environmental law and environmental justice demonstrate the model’s predictive power for the formation of new distinct legal regimes. Part II applies the Stationarity Assessment model to the topic of climate change adaptation, using a case study of a hypothetical coastal region and the potential for climate change impacts to disrupt relevant legal doctrines and institutions. We find that most fields of law appear capable of adapting effectively to climate change. In other words, without some active intervention, we expect the law and policy of climate change adaptation to follow the path of the Law of the Horse - a collection of fields independently adapting to climate change - rather than organically coalescing into a new distinct field. Part III explores why, notwithstanding this conclusion, it may still be desirable to seek a different trajectory. Focusing on the likelihood of systemic adaptation decisions with perverse, harmful results, we identify the potential benefits offered by intervening to shape a new and distinct field of climate change adaptation law and policy. Part IV then identifies the contours of such a field, exploring the distinct purposes of reducing vulnerability, ensuring resiliency, and safeguarding equity. These features provide the normative policy components for a law of climate change adaptation that would be more than just a Law of the Horse. This new field would not replace or supplant any existing field, however, as environmental law did with regard to nuisance law, and it would not be dominated by substantive doctrine. Rather, like the field of environmental justice, this new legal regime would serve as a holistic overlay across other fields to ensure more efficient, effective, and just climate change adaptation solutions

Demand-side financing for maternal and newborn health: what do we know about factors that affect implementation of cash transfers and voucher programmes?

BackgroundDemand-side financing (DSF) interventions, including cash transfers and vouchers, have been introduced to promote maternal and newborn health in a range of low- and middle-income countries. These interventions vary in design but have typically been used to increase health service utilisation by offsetting some financial costs for users, or increasing household income and incentivising 'healthy behaviours'. This article documents experiences and implementation factors associated with use of DSF in maternal and newborn health.MethodsA secondary analysis (using an adapted Supporting the Use of Research Evidence framework - SURE) was performed on studies that had previously been identified in a systematic review of evidence on DSF interventions in maternal and newborn health.ResultsThe article draws on findings from 49 quantitative and 49 qualitative studies. The studies give insights on difficulties with exclusion of migrants, young and multiparous women, with demands for informal fees at facilities, and with challenges maintaining quality of care under increasing demand. Schemes experienced difficulties if communities faced long distances to reach participating facilities and poor access to transport, and where there was inadequate health infrastructure and human resources, shortages of medicines and problems with corruption. Studies that documented improved care-seeking indicated the importance of adequate programme scope (in terms of programme eligibility, size and timing of payments and voucher entitlements) to address the issue of concern, concurrent investments in supply-side capacity to sustain and/or improve quality of care, and awareness generation using community-based workers, leaders and women's groups. ConclusionsEvaluations spanning more than 15 years of implementation of DSF programmes reveal a complex picture of experiences that reflect the importance of financial and other social, geographical and health systems factors as barriers to accessing care. Careful design of DSF programmes as part of broader maternal and newborn health initiatives would need to take into account these barriers, the behaviours of staff and the quality of care in health facilities. Research is still needed on the policy context for DSF schemes in order to understand how they become sustainable and where they fit, or do not fit, with plans to achieve equitable universal health coverage

Effects of demand-side financing on utilisation, experiences and outcomes of maternity care in low- and middle-income countries: a systematic review.

Demand-side financing, where funds for specific services are channelled through, or to, prospective users, is now employed in health and education sectors in many low- and middle-income countries. This systematic review aimed to critically examine the evidence on application of this approach to promote maternal health in these settings. Five modes were considered: unconditional cash transfers, conditional cash transfers, short-term payments to offset costs of accessing maternity services, vouchers for maternity services, and vouchers for merit goods. We sought to assess the effects of these interventions on utilisation of maternity services and on maternal health outcomes and infant health, the situation of underprivileged women and the healthcare system

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Neptune Odyssey: A Flagship Concept for the Exploration of the Neptune–Triton System

The Neptune Odyssey mission concept is a Flagship-class orbiter and atmospheric probe to the Neptune-Triton system. This bold mission of exploration would orbit an ice-giant planet to study the planet, its rings, small satellites, space environment, and the planet-sized moon Triton. Triton is a captured dwarf planet from the Kuiper Belt, twin of Pluto, and likely ocean world. Odyssey addresses Neptune system-level science, with equal priorities placed on Neptune, its rings, moons, space environment, and Triton. Between Uranus and Neptune, the latter is unique in providing simultaneous access to both an ice giant and a Kuiper Belt dwarf planet. The spacecraft - in a class equivalent to the NASA/ESA/ASI Cassini spacecraft - would launch by 2031 on a Space Launch System or equivalent launch vehicle and utilize a Jupiter gravity assist for a 12 yr cruise to Neptune and a 4 yr prime orbital mission; alternatively a launch after 2031 would have a 16 yr direct-to-Neptune cruise phase. Our solution provides annual launch opportunities and allows for an easy upgrade to the shorter (12 yr) cruise. Odyssey would orbit Neptune retrograde (prograde with respect to Triton), using the moon's gravity to shape the orbital tour and allow coverage of Triton, Neptune, and the space environment. The atmospheric entry probe would descend in ~37 minutes to the 10 bar pressure level in Neptune's atmosphere just before Odyssey's orbit-insertion engine burn. Odyssey's mission would end by conducting a Cassini-like "Grand Finale,"passing inside the rings and ultimately taking a final great plunge into Neptune's atmosphere

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]