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The development and strengthening of health technology assessment (HTA) capacity on the individual and organizational level and the wider environment is relevant for cooperation on HTAs. Based on the Maltese case, we provide a blueprint for building HTA capacity.
Methods
A set of activities were developed based on Pichler et al.’s framework and the starting HTA capacity in Malta. Individual level activities focused on strengthening epidemiological and health economic skills through online and in-person training. On the organizational level, a new HTA framework was developed which was subsequently utilized in a shadow assessment. Awareness campaign activities raised awareness and support in the wider environment where HTAs are conducted and utilized.
Results
The time needed to build HTA capacity exceeded the planned two years accommodating the learning progress of the assessors. In addition to the planned trainings, webinars supplemented the online courses, allowing for more knowledge exchange. The advanced online course was extended over time to facilitate learning next to the assessors’ daily tasks. Training sessions were added to implement the new economic evaluation framework, which was utilized in a second shadow assessment. Awareness by decision-makers was achieved with reports, posters, and an article on the current and developing HTA capacity.
Conclusions
It takes time and much (hands-on) training to build skills for conducting complex assessment such as HTAs. Facilitating exchange with knowledgeable parties is crucial for succeeding as well as the buy-in of local managers motivating staff. Decision-makers need to be on-boarded for the continued success of HTA capacity building.
Childhood trauma may impact the course of schizophrenia spectrum disorders (SSD), specifically in relation to the increased severity of depressive or negative symptoms. The type and impact of trauma may differ between sexes. In a large sample of recent-onset patients, we investigated the associations of depressive and negative symptoms with childhood trauma and whether these are sex-specific.
Methods
A total of 187 first-episode psychosis patients in remission (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment study) and 115 recent-onset SSD patients (Simvastatin study) were included in this cross-sectional study (men: n = 218; women: n = 84). Total trauma score and trauma subtypes were assessed using the Childhood Trauma Questionnaire Short Form; depressive and negative symptoms were rated using the Positive And Negative Symptoms Scale. Sex-specific regression analyses were performed.
Results
Women reported higher rates of sexual abuse than men (23.5% v. 7.8%). Depressive symptoms were associated with total trauma scores and emotional abuse ratings in men (β: 0.219–0.295; p ≤ 0.001). In women, depressive symptoms were associated with sexual abuse ratings (β: 0.271; p = 0.011). Negative symptoms were associated with total trauma score and emotional neglect ratings in men (β: 0.166–0.232; p ≤ 0.001). Negative symptoms in women were not linked to childhood trauma, potentially due to lack of statistical power.
Conclusions
Depressive symptom severity was associated with different types of trauma in men and women with recent-onset SSD. Specifically, in women, depressive symptom severity was associated with childhood sexual abuse, which was reported three times as often as in men. Our results emphasize the importance of sex-specific analyses in SSD research.
Most European countries use Health Technology Assessment (HTA) as input for decisions on reimbursement of (new) medicines. In 2018, following the approval of European Social Funding, the Directorate for Pharmaceutical Affairs (DPA) within the Malta Ministry for Health led a specific Work Package aimed at enhancing knowledge, skills and HTA processes to inform reimbursement decisions.
Methods
Since the start of the project, the Institute for Medical Technology Assessment (iMTA) and the National Health Care Institute of the Netherlands (ZIN) collaborate in providing guidance and training to DPA on relative effectiveness assessments (REAs) and pharmacoeconomic assessments (PEAs) of pharmaceuticals. Several activities were organized: site visits, face-to face interviews with stakeholders, a qualitative assessment of the core process of the Maltese system, health economics training and tutorials, meetings introducing the European Network for Health Technology Assessment (EUnetHTA) and Dutch HTA processes, development of a new framework for assessment, and a shadow assessment.
Results
Our assessment identified important methodological challenges and crucial processes interdependencies to optimize within the Maltese system. Based on the learnings, DPA created a template based on the EUnetHTA REA assessment format. IMTA created a template to perform PEAs. Currently, a shadow assessment is ongoing in which DPA performs the REA and PEA of a pharmaceutical using the new templates. ZIN and iMTA will provide feedback to DPA on several aspects, including, but not limited to, the PICO, assessment of therapeutic efficacy and safety, identifying uncertainties, input costs and effects, and formulating a clear discussion of the assessment. If necessary, the templates will be adapted during the process. The project will be evaluated and finalized in 2022.
Conclusions
With the guidance and training provided by iMTA and ZIN, DPA structured and aligned their REA and PEA to enhance their assessment process and to improve the presentation of their HTA report to the two appraisal committees. This project emphasizes the importance of international collaboration to enhance HTA processes within the
Reimbursement decision making is based on a relative effectiveness assessment (REA), which may be combined with a cost-effectiveness assessment, by national Health Technology Assessment (HTA) agencies. These assessments are based on clinical data where new interventions are compared to the current standard of care, which may differ between countries. Since most pivotal trials only include a limited number of interventions, indirect treatment comparisons (ITCs) can be used to compare multiple interventions. The aim of this study was to evaluate the use of ITCs in HTA decision making in the Netherlands and England.
Methods
All pharmaceutical assessments published between 2015 and 2019 by the National Health Care Institute (ZIN) and the National Institute for Health and Care Excellence (NICE) were reviewed to determine whether an ITC had been used. For detailed analysis we included all assessments of ZIN using an ITC, and a random sample of assessments of NICE using an ITC (10 assessments per publication year).
Results
Between 2015 and 2019 a total of 106 and 265 assessments were conducted by ZIN and NICE, respectively. Of these assessments 48 from ZIN and 150 from NICE included an ITC. The detailed analysis showed that pharmaceutical assessments including indirect comparative evidence led to the REA conclusion of similar therapeutic evidence in 57 percent of 48 assessments by ZIN and in 52 percent of 50 assessments by NICE. Reimbursement recommendations including indirect comparative evidence most often resulted in positive recommendations by ZIN (57% assessments), and in restricted recommendations by NICE (50% assessments). Different methods were employed to incorporate indirect comparative evidence, such as naïve ITCs and network meta-analysis.
Conclusions
Our results showed a significant variability in the use of ITCs between NICE and ZIN, which may contribute to differences in their recommendations. Further analysis will provide deeper insight in these differences and may provide suggestions for a clearer international guidance on the use of ITCs for HTA.
Antisociality across adolescence and young adulthood puts individuals at high risk of developing a variety of problems. Prior research has linked antisociality to autonomic nervous system and endocrinological functioning. However, there is large heterogeneity in antisocial behaviors, and these neurobiological measures are rarely studied conjointly, limited to small specific studies with narrow age ranges, and yield mixed findings due to the type of behavior examined.
Methods
We harmonized data from 1489 participants (9–27 years, 67% male), from six heterogeneous samples. In the resulting dataset, we tested relations between distinct dimensions of antisociality and heart rate, pre-ejection period (PEP), respiratory sinus arrhythmia, respiration rate, skin conductance levels, testosterone, basal cortisol, and the cortisol awakening response (CAR), and test the role of age throughout adolescence and young adulthood.
Results
Three dimensions of antisociality were uncovered: ‘callous-unemotional (CU)/manipulative traits’, ‘intentional aggression/conduct’, and ‘reactivity/impulsivity/irritability’. Shorter PEPs and higher testosterone were related to CU/manipulative traits, and a higher CAR is related to both CU/manipulative traits and intentional aggression/conduct. These effects were stable across age.
Conclusions
Across a heterogeneous sample and consistent across development, the CAR may be a valuable measure to link to CU/manipulative traits and intentional aggression, while sympathetic arousal and testosterone are additionally valuable to understand CU/manipulative traits. Together, these findings deepen our understanding of the fundamental mechanisms underlying different components of antisociality. Finally, we illustrate the potential of using current statistical techniques for combining multiple datasets to draw robust conclusions about biobehavioral associations.
A brief overview of the current radio source host galaxy state of affairs is given. All the evidence appears to point towards a scenario in which the young radio source expands through the host galaxy on timescales of 105–106 yr, before it ends its life as a large scale FR II radio galaxy. The place and role of the quasars in this evolutionary picture is unclear, however, and remains an issue of debate.
Nitrogen (N) budgets of agricultural systems give important information for assessing the impact of N inputs on the environment, and identify levers for action.
Approaches
N budgets of agro-ecosystems in the 27 EU countries are established for the year 2000, considering N inputs by fertiliser application, manure excretion, atmospheric deposition and crop fixation, and N outputs by plant uptake, gaseous emissions, mineralisation, leaching and runoff.
Country N budgets for agro-ecosystems are based on the models INTEGRATOR, IDEAg, MITERRA and IMAGE. Fine geographic distribution is depicted with the former two models, which have higher spatial resolution. INTEGRATOR is the only available model for calculating non-agricultural terrestrial N budgets systems.
Key findings/state of knowledge
For EU-27, the models estimate a comparable total N input in European agriculture, i.e. 23.3–25.7 Mton N yr−1, but N uptake varies largely from 11.3–15.4 Mton N yr−1, leading to total N surpluses varying from 10.4–13.2 Mton N yr−1. Despite this variation, the overall difference at EU-27 is small for the emissions of NH3 (2.8–3.1 Mton N yr−1) and N2O (0.33–0.43 Mton N yr−1) but estimates vary largely at a regional scale. The estimated sum of N leaching and runoff at EU-27 is roughly equal to the sum of NH3, N2O and NOx emissions to the atmosphere, but estimates vary by a factor two, from 2.7 to 6.3 Mton N yr−1.
Reactive nitrogen (Nr) is of fundamental importance in biological and chemical processes in the atmosphere–biosphere system, altering the Earth's climate balance in many ways. These include the direct and indirect emissions of nitrous oxide (N2O), atmospheric Nr deposition and tropospheric ozone formation (O3), both of which alter the biospheric CO2 sink, Nr supply effects on CH4 emissions, and the formation of secondary atmospheric aerosols resulting from the emissions of nitrogen oxides (NOx) and ammonia (NH3).
Human production and release of Nr into the environment is thus expected to have been an important driver of European greenhouse balance. Until now, no assessment has been made of how much of an effect European Nr emissions are having on net warming or cooling.
Approaches
This chapter summarizes current knowledge of the role of Nr for global warming. Particular attention is given to the consequences of atmospheric Nr emissions. The chapter draws on inventory data and review of the literature to assess the contribution of anthropogenic atmospheric Nr emissons to the overall change in radiative forcing (between 1750 and 2005) that can be attributed to activities in Europe.
The use of Nr fertilizers has major additional effects on climate balance by allowing increased crop and feed production and larger populations of livestock and humans, but these indirect effects are not assessed here.
The transfer of nitrogen by either farm management activities or natural processes (through the atmosphere and the hydrological network) can feed into the N cascade and lead to indirect and unexpected reactive nitrogen emissions.
This transfer can lead to large N deposition rates and impacts to sensitive ecosystems. It can also promote further N2O emission in areas where conditions are more favourable for denitrification.
In rural landscapes, the relevant scale is the scale where N is managed by farm activities and where environmental measures are applied.
Approaches
Mitigating nitrogen at landscape scale requires consideration of the interactions between natural and anthropogenic (i.e. farm management) processes.
Owing to the complex nature and spatial extent of rural landscapes, experimental assessments of reactive N flows at this scale are difficult and often incomplete. It should include measurement of N flows in the different compartments of the environment and comprehensive datasets on the environment (soils, hydrology, land use, etc.) and on farm management.
Modelling is the preferred tool to investigate the complex relationships between anthropogenic and natural processes at landscape scale although verification by measurements is required. Up to now, no model includes all the components of landscape scale N flows: farm functioning, short range atmospheric transfer, hydrology and ecosystem modelling.
Biodiversity is the variability among living organisms, from genes to the biosphere. The value of biodiversity is multifold, from preserving the integrity of the biosphere as a whole, to providing food and medicines, to spiritual and aesthetic well-being.
One of the major drivers of biodiversity loss in Europe is atmospheric deposition of reactive nitrogen (Nr).
Approaches
This chapter focuses on Nr impacts on European plant species diversity; in particular, the number and abundance of different species in a given area, and the presence of characteristic species of sensitive ecosystems.
We summarise both the scientific and the policy aspects of Nr impacts on diversity and identify, using a range of evidence, the most vulnerable ecosystems and regions in Europe.
Key findings/state of knowledge
Reactive nitrogen impacts vegetation diversity through direct foliar damage, eutrophication, acidification, and susceptibility to secondary stress.
Species and communities most sensitive to chronically elevated Nr deposition are those that are adapted to low nutrient levels, or are poorly buffered against acidification. Grassland, heathland, peatland, forest, and arctic/montane ecosystems are recognised as vulnerable habitats in Europe; other habitats may be vulnerable but are still poorly studied.
It is not yet clear if different wet-deposited forms of Nr (e.g. nitrate, NO3− versus ammonium, NH4+) have different effects on biodiversity. However, gaseous ammonia (NH3) can be particularly harmful to vegetation, especially lower plants, through direct foliar damage.
Environmental problems related to nitrogen concern all economic sectors and impact all media: atmosphere, pedosphere, hydrosphere and anthroposphere.
Therefore, the integration of fluxes allows an overall coverage of problems related to reactive nitrogen (Nr) in the environment, which is not accessible from sectoral approaches or by focusing on specific media.
Approaches
This chapter presents a set of high resolution maps showing key elements of the N flux budget across Europe, including N2 and Nr fluxes.
Comparative nitrogen budgets are also presented for a range of European countries, highlighting the most efficient strategies for mitigating Nr problems at a national scale. A new European Nitrogen Budget (EU-27) is presented on the basis of state-of-the-art Europe-wide models and databases focusing on different segments of Europe's society.
Key findings
From c. 18 Tg Nr yr−1 input to agriculture in the EU-27, only about 7 Tg Nr yr−1 find their way to the consumer or are further processed by industry.
Some 3.7 Tg Nr yr−1 is released by the burning of fossil fuels in the EU-27, whereby the contribution of the industry and energy sectors is equal to that of the transport sector. More than 8 Tg Nr yr−1 are disposed of to the hydrosphere, while the EU-27 is a net exporter of reactive nitrogen through atmospheric transport of c. 2.3 Tg Nr yr−1.
The largest single sink for Nr appears to be denitrification to N2 in European coastal shelf regions (potentially as large as the input of mineral fertilizer, about 11 Tg N yr–1 for the EU-27); however, this sink is also the most uncertain, because of the uncertainty of Nr import from the open ocean.
A large part of agricultural soils in Europe are exposed to high N inputs because of animal manure and chemical fertiliser use. Large parts of the European natural soils are exposed to high atmospheric N deposition.
High N inputs threaten soil quality, which may negatively affect food and biomass production and biodiversity and enhance emissions of harmful N compounds from soils to water and the atmosphere.
Approaches
An overview of the major soil functions and soil threats are presented, including a description of the objectives of the European Soil Strategy.
The major N threats on soil quality for both agricultural and natural soils are related to changes in soil organic content and quality, soil acidification, and loss of soil diversity. These threats are described using literature.
Key findings/state of knowledge
Generally, N has a positive effect on soil quality of agricultural soils, because it enhances soil fertility and conditions for crop growth. However, it generally has a negative effect on soil quality of natural soils, because it results in changes in plant diversity.
Soil acts as a filter and buffer for N, and protects water and atmosphere against N pollution. However, the filter and buffer capacity of soils is frequently exceeded by excess of N in both agricultural and natural soils, which results in emission of N to the environment.
The future effects of nitrogen in the environment will depend on the extent of nitrogen use and the practical application techniques of nitrogen in a similar way as in the past. Projections and scenarios are appropriate tools for extrapolating current knowledge into the future. However, these tools will not allow future system turnovers to be predicted.
Approaches
In principle, scenarios of nitrogen use follow the approaches currently used for air pollution, climate, or ecosystem projections. Short-term projections (to 2030) are developed using a ‘baseline’ path of development, which considers abatement options that are consistent with European policy. For medium-term projections (to 2050) and long-term projections, the European Nitrogen Assessment (ENA) applies a ‘storyline’ approach similar to that used in the IPCC SRES scenarios. Beyond 2050 in particular, such storylines also take into account technological and behavioral shifts.
Key findings/state of knowledge
The ENA distinguishes between driver-oriented and effect-oriented factors determining nitrogen use. Parameters that cause changes in nitrogen fixation or application are called drivers. In a driver-based approach, it is assumed that any variation of these parameters will also trigger a change in nitrogen pollution. In an effect-based approach, as the adverse effects of nitrogen become evident in the environment, introduction of nitrogen abatement legislation requiring the application of more efficient abatement measures is expected. This approach needs to rely on a target that is likely to be maintained in the future (e.g. human health). Nitrogen abatement legislation based on such targets will aim to counter any growth in adverse environmental effects that occur as a result of increased nitrogen application.
Air pollution is known to have a range of effects, including those on human health, crop production, soil acidification, visibility and corrosion of materials. This Chapter focuses on the two major impacts of air pollution that have most strongly influenced the development of policies to reduce emissions: those on the natural environment and on human health.
In broad terms, the major impacts of air pollution on the natural environment can be placed into three categories, representing different spatial scales:
Local impacts of major industrial or urban sources, for example, instances of damage to ecosystems and crop production close to emission sources. Historically, the biggest impacts have been through the direct effects of sulphur dioxide and particles – either around large point sources such as power stations and smelters, or in urban areas with domestic coal burning – and the accumulation of toxic metals in soils around smelters. However, a range of other pollutants from specific local sources can have direct impacts on vegetation.
Regional impacts of ozone, which is a significant global air pollutant in terms of impacts on vegetation, since high concentrations are found in rural areas.
Regional impacts of long-Range Transport and deposition of sulphur and nitrogen, which have effects on soil acidity, nutrient availability and water chemistry, and hence on ecosystem composition and function.
The Chapter first considers direct effects of air pollution on vegetation and the visible symptoms of damage that can result, illustrating the spatial variation in damage by reference to national and local studies in the Netherlands.
We discuss obbservations and numerical simulations which show that radiative shocks in jet-cloud collisions can trigger the collapse of intergalactic clouds and subsequent star formation in low luminosity, ‘FR-I’ type, radio galaxies.To search for other articles by the author(s) go to: http://adsabs.harvard.edu/abstract_service.html
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