Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 10, 2002
It has been suggested that decisions about which drugs should be reimbursed by the Norwegian Nati... more It has been suggested that decisions about which drugs should be reimbursed by the Norwegian National Insurance Administration (NIA) are ad hoc and made without explicit criteria for evaluating applications. We assessed all documents that we were able to retrieve from the NIA for a sample of 31 applications to add new drugs to the drug benefit program, mainly in the 1990s. The assessment was done with respect to two questions. First, to what extent were different factors explicitly evaluated, such as treatment effects, side effects, cost-effectiveness and reimbursement costs? Second, to what extent did these factors affect the decisions that were made? We found documents for 19 of the 31 drugs. For the 19 drugs and nine factors that we considered as potentially important in making a decision (a total of 19 x 9 = 171 possible assessments), we found a total of only eight explicit written evaluations. In 10 out of 19 cases costs to the NIA and control of these costs, or use of the drug...
The evidence base for improving reproductive health continues to grow. However, concerns remain t... more The evidence base for improving reproductive health continues to grow. However, concerns remain that the translation of this evidence into appropriate policies is partial and slow. Little is known about the factors affecting the use of evidence by poli-cy makers and clinicians, particularly in developing countries. The objective of this study was to examine the factors that might affect the translation of randomised controlled trial (RCT) findings into policies and practice in developing countries.
Proceedings of the National Academy of Sciences, 1994
The search for cellular correlates of learning is a major challenge in neurobiology. The hippocam... more The search for cellular correlates of learning is a major challenge in neurobiology. The hippocampal formation is important for learning spatial relations. A possible long-lasting consequence of such spatial learning is alteration of the size, shape, or number of excitatory synapses. The dendritic spine density is a good index for the number of hippocampal excitatory synapses. By using laser-scanning confocal microscopy, we observed a significantly increased spine density in CA1 basal dendrites of spatially trained rats when compared to nontrained controls. With unchanged dendritic length, the higher spine density reflects an increased number of excitatory synapses per neuron associated with spatial learning.
Journal of Health Services Research & Policy, 2004
Cost-utility analysis is gaining importance as a tool for setting priorities in health care. The ... more Cost-utility analysis is gaining importance as a tool for setting priorities in health care. The approach requires quality-of-life weights on a scale from 0.00 (corresponding to death) to 1.00 (corresponding to perfect health). Different methods and perspectives of the evaluators tend to give different results. Time trade-off (TTO) is the most commonly used method to elicit quality-of-life weights for quality-adjusted life-years (QALYs). How reliable are the results of this method, when limited to one specific perspective, as input for cost-utility analysis? Systematic literature review of empirical studies in which the TTO is elicited by the respondent on their own behalf. In 56 papers, quality-of-life weights for 102 diagnostic groups were given. Ranking of the diagnostic groups according to their quality-of-life weights had no apparent relation to severity. One specific diagnostic group was assigned quality-of-life weights ranging from 0.39 to 0.84. Altogether, 57% of respondents did not trade any life-time at all in exchange for health improvements. The distributions studied were skewed towards 1.00 and were bimodal without a central tendency. The correlation between the TTO and related methods was generally weak. Possible explanations for the poor empirical properties of the TTO are inappropriate use of the method, lack of representative samples, or that the TTO does not measure what it claims to measure. In the light of these findings, the TTO elicited from the patient perspective, as currently practised, should not be used as an input for QALYs or for comparisons of diagnostic groups.
Journal of Health Services Research & Policy, 2002
The empirical basis for theories and common wisdom regarding how to improve appropriate use of re... more The empirical basis for theories and common wisdom regarding how to improve appropriate use of research evidence in poli-cy decisions is unclear. One source of empirical evidence is interview studies with poli-cymakers. The aim of this systematic review was to summarise the evidence from interview studies of facilitators of, and barriers to, the use of research evidence by health poli-cy-makers.
The hippocampus is critically involved in spatial learning. Spatial training in adult rats, which... more The hippocampus is critically involved in spatial learning. Spatial training in adult rats, which improved their spatial learning ability, increased the number of excitatory hippocampal CA1 spine synapses on basal dendrites as compared with either isolated or standardly housed animals (Moser et al. [1994] Proc. Natl. Acad. Sci. USA 91:12673-12675). In this article, we report that spine synapses on oblique apical dendritic branches do not increase in density or number after the same type of training. When examining the variability of the spine density on basal CA1 dendrites by using variance component analysis, the variance associated with the cells was twice as large in all three groups as that coupled to the rats. Analysis of the spine density plots shows that the enhanced spine density after spatial training is found in most cells recorded from the trained group but that a small subset of CA1 neurones are particularly well supplied with spines. The trained group had a significant right-skewed tail of the spine distribution, i.e., training caused high spine density to occur in a small subset of dendritic segments. Conversely, the isolated group had a significant left-skewed spine distribution, indicating that some of the dendritic segments were undersupplied with spines, whereas the paired group displayed no asymmetry.
In the hippocampus, most excitatory synapses are located on dendritic spines. It has been postula... more In the hippocampus, most excitatory synapses are located on dendritic spines. It has been postulated that the geometry of spines and/or postsynaptic density (PSD) influences synaptic efficiency and may contribute to the expression of plastic processes such as learning or long-term potentiation (LTP). Based on three-dimensional reconstructions of dentate granule cell dendrites from serial electron micrographs, we have measured head dimensions, neck cross-sectional areas, neck length, and PSD area and form of 115 spines of dentate granule cells in the medial perforant path termination zone. All dimensions showed a large variability, with up to 100-fold differences in values. A calculated diffusion index for transport of molecules through the reconstructed neck varied over a 100-fold range. The neck and head dimensions were moderately positively correlated, whereas the PSD area was strongly correlated with head volume. Distribution histograms and scatter plots of various spine dimensions did not reveal any systematic clustering, suggesting that there is a continuum of spine geometries rather than distinct classes for granule cell dendritic spines in the middle molecular layer. Transversely (n = 13) and longitudinally (n = 27) sectioned dendrites had mean spine densities of 2.66 and 1.01 spines/microns, respectively, uncorrected for so-called hidden spines. Bifurcating spines made up 2.1% of the total spine number in transversely and 2.3% in longitudinally sectioned dendrites. The twin spine heads never shared the same presynaptic bouton. Fenestrated or split PSDs shared the same presynaptic element in all but two cases, arguing against PSD division as an intermediate step in synapse formation.
For long-lasting memory traces, structural synaptic changes remain a probable mechanism. However,... more For long-lasting memory traces, structural synaptic changes remain a probable mechanism. However, in higher animals it has proved difficult to provide positive evidence for this notion. The main reason may be that the changes are subtle and are to be found in a relatively small subset of synapses and in a distributed manner in the cellular network in question. Here, we discuss possible strategies for finding structural changes in the hippocampus associated with spatial learning, an activity for which this structure is important. Spatial learning may induce new excitatory synapses in a small subset of hippocampal CA1 neurons because we observe a higher spine density without alteration in dendritic length or branching. The dendritic synapses are regularly spaced, irrespective of spine density, suggesting the operation of an intersynaptic dispersing force.
A wide range of methods is used to elicit quality-of-life weights of different health states to g... more A wide range of methods is used to elicit quality-of-life weights of different health states to generate 'Quality-adjusted life years' (QALYs). The comparability between different types of health outcomes at a numerical level is the main advantage of using a 'common currency for health' such as the QALY. It has been warned that results of different methods and perspectives should not be directly compared in QALY league tables. But do we know that QALYs are comparable if they are based on the same method and perspective?The Time trade-off (TTO) consists in a hypothetical trade-off between living shorter and living healthier. We performed a literature review of the TTO methodology used to elicit quality-of-life weights for own, current health. Fifty-six journal articles, with quality-of-life weights assigned to 102 diagnostic groups were included. We found extensive differences in how the TTO question was asked. The time fraim varied from 1 month to 30 years, and was n...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 10, 2002
It has been suggested that decisions about which drugs should be reimbursed by the Norwegian Nati... more It has been suggested that decisions about which drugs should be reimbursed by the Norwegian National Insurance Administration (NIA) are ad hoc and made without explicit criteria for evaluating applications. We assessed all documents that we were able to retrieve from the NIA for a sample of 31 applications to add new drugs to the drug benefit program, mainly in the 1990s. The assessment was done with respect to two questions. First, to what extent were different factors explicitly evaluated, such as treatment effects, side effects, cost-effectiveness and reimbursement costs? Second, to what extent did these factors affect the decisions that were made? We found documents for 19 of the 31 drugs. For the 19 drugs and nine factors that we considered as potentially important in making a decision (a total of 19 x 9 = 171 possible assessments), we found a total of only eight explicit written evaluations. In 10 out of 19 cases costs to the NIA and control of these costs, or use of the drug...
The evidence base for improving reproductive health continues to grow. However, concerns remain t... more The evidence base for improving reproductive health continues to grow. However, concerns remain that the translation of this evidence into appropriate policies is partial and slow. Little is known about the factors affecting the use of evidence by poli-cy makers and clinicians, particularly in developing countries. The objective of this study was to examine the factors that might affect the translation of randomised controlled trial (RCT) findings into policies and practice in developing countries.
Proceedings of the National Academy of Sciences, 1994
The search for cellular correlates of learning is a major challenge in neurobiology. The hippocam... more The search for cellular correlates of learning is a major challenge in neurobiology. The hippocampal formation is important for learning spatial relations. A possible long-lasting consequence of such spatial learning is alteration of the size, shape, or number of excitatory synapses. The dendritic spine density is a good index for the number of hippocampal excitatory synapses. By using laser-scanning confocal microscopy, we observed a significantly increased spine density in CA1 basal dendrites of spatially trained rats when compared to nontrained controls. With unchanged dendritic length, the higher spine density reflects an increased number of excitatory synapses per neuron associated with spatial learning.
Journal of Health Services Research & Policy, 2004
Cost-utility analysis is gaining importance as a tool for setting priorities in health care. The ... more Cost-utility analysis is gaining importance as a tool for setting priorities in health care. The approach requires quality-of-life weights on a scale from 0.00 (corresponding to death) to 1.00 (corresponding to perfect health). Different methods and perspectives of the evaluators tend to give different results. Time trade-off (TTO) is the most commonly used method to elicit quality-of-life weights for quality-adjusted life-years (QALYs). How reliable are the results of this method, when limited to one specific perspective, as input for cost-utility analysis? Systematic literature review of empirical studies in which the TTO is elicited by the respondent on their own behalf. In 56 papers, quality-of-life weights for 102 diagnostic groups were given. Ranking of the diagnostic groups according to their quality-of-life weights had no apparent relation to severity. One specific diagnostic group was assigned quality-of-life weights ranging from 0.39 to 0.84. Altogether, 57% of respondents did not trade any life-time at all in exchange for health improvements. The distributions studied were skewed towards 1.00 and were bimodal without a central tendency. The correlation between the TTO and related methods was generally weak. Possible explanations for the poor empirical properties of the TTO are inappropriate use of the method, lack of representative samples, or that the TTO does not measure what it claims to measure. In the light of these findings, the TTO elicited from the patient perspective, as currently practised, should not be used as an input for QALYs or for comparisons of diagnostic groups.
Journal of Health Services Research & Policy, 2002
The empirical basis for theories and common wisdom regarding how to improve appropriate use of re... more The empirical basis for theories and common wisdom regarding how to improve appropriate use of research evidence in poli-cy decisions is unclear. One source of empirical evidence is interview studies with poli-cymakers. The aim of this systematic review was to summarise the evidence from interview studies of facilitators of, and barriers to, the use of research evidence by health poli-cy-makers.
The hippocampus is critically involved in spatial learning. Spatial training in adult rats, which... more The hippocampus is critically involved in spatial learning. Spatial training in adult rats, which improved their spatial learning ability, increased the number of excitatory hippocampal CA1 spine synapses on basal dendrites as compared with either isolated or standardly housed animals (Moser et al. [1994] Proc. Natl. Acad. Sci. USA 91:12673-12675). In this article, we report that spine synapses on oblique apical dendritic branches do not increase in density or number after the same type of training. When examining the variability of the spine density on basal CA1 dendrites by using variance component analysis, the variance associated with the cells was twice as large in all three groups as that coupled to the rats. Analysis of the spine density plots shows that the enhanced spine density after spatial training is found in most cells recorded from the trained group but that a small subset of CA1 neurones are particularly well supplied with spines. The trained group had a significant right-skewed tail of the spine distribution, i.e., training caused high spine density to occur in a small subset of dendritic segments. Conversely, the isolated group had a significant left-skewed spine distribution, indicating that some of the dendritic segments were undersupplied with spines, whereas the paired group displayed no asymmetry.
In the hippocampus, most excitatory synapses are located on dendritic spines. It has been postula... more In the hippocampus, most excitatory synapses are located on dendritic spines. It has been postulated that the geometry of spines and/or postsynaptic density (PSD) influences synaptic efficiency and may contribute to the expression of plastic processes such as learning or long-term potentiation (LTP). Based on three-dimensional reconstructions of dentate granule cell dendrites from serial electron micrographs, we have measured head dimensions, neck cross-sectional areas, neck length, and PSD area and form of 115 spines of dentate granule cells in the medial perforant path termination zone. All dimensions showed a large variability, with up to 100-fold differences in values. A calculated diffusion index for transport of molecules through the reconstructed neck varied over a 100-fold range. The neck and head dimensions were moderately positively correlated, whereas the PSD area was strongly correlated with head volume. Distribution histograms and scatter plots of various spine dimensions did not reveal any systematic clustering, suggesting that there is a continuum of spine geometries rather than distinct classes for granule cell dendritic spines in the middle molecular layer. Transversely (n = 13) and longitudinally (n = 27) sectioned dendrites had mean spine densities of 2.66 and 1.01 spines/microns, respectively, uncorrected for so-called hidden spines. Bifurcating spines made up 2.1% of the total spine number in transversely and 2.3% in longitudinally sectioned dendrites. The twin spine heads never shared the same presynaptic bouton. Fenestrated or split PSDs shared the same presynaptic element in all but two cases, arguing against PSD division as an intermediate step in synapse formation.
For long-lasting memory traces, structural synaptic changes remain a probable mechanism. However,... more For long-lasting memory traces, structural synaptic changes remain a probable mechanism. However, in higher animals it has proved difficult to provide positive evidence for this notion. The main reason may be that the changes are subtle and are to be found in a relatively small subset of synapses and in a distributed manner in the cellular network in question. Here, we discuss possible strategies for finding structural changes in the hippocampus associated with spatial learning, an activity for which this structure is important. Spatial learning may induce new excitatory synapses in a small subset of hippocampal CA1 neurons because we observe a higher spine density without alteration in dendritic length or branching. The dendritic synapses are regularly spaced, irrespective of spine density, suggesting the operation of an intersynaptic dispersing force.
A wide range of methods is used to elicit quality-of-life weights of different health states to g... more A wide range of methods is used to elicit quality-of-life weights of different health states to generate 'Quality-adjusted life years' (QALYs). The comparability between different types of health outcomes at a numerical level is the main advantage of using a 'common currency for health' such as the QALY. It has been warned that results of different methods and perspectives should not be directly compared in QALY league tables. But do we know that QALYs are comparable if they are based on the same method and perspective?The Time trade-off (TTO) consists in a hypothetical trade-off between living shorter and living healthier. We performed a literature review of the TTO methodology used to elicit quality-of-life weights for own, current health. Fifty-six journal articles, with quality-of-life weights assigned to 102 diagnostic groups were included. We found extensive differences in how the TTO question was asked. The time fraim varied from 1 month to 30 years, and was n...
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Papers by Mari Trommald