Search

Additional file 1. Details of search strategy. This file provides a detailed description of the search strategy used for finding studies.

Additional file 1.

Additional file 2. Characteristic of included studies. This file provides the characteristics of the included studies in a table form, including first author, year of publication, country, study design, study subject, sample size, sampling method, mean age/age range, setting, tools for measurements, outcome, result and quality rate.

Additional file 2. GP interview guide

Additional file 3. Patient interview guide (in Danish)

The present study investigated effects of various commercial diets, of protein and of fat 1evels in semisynthetic diets, and of fiber content and type on hepatic O-deethylation of p-nitrophenetole in mice. A high fat content increased and a high fiber content decreased the hepatic p-nitrophenetole O-deethylation activity. The activity in mice kept on different commercial feedings differed significantly. The level of hepatic microsomal cytochrome P-450 activity affects the toxicity of many compounds. Thus, standardization of commercial feeds for experimental animals used in toxicological and pharmacological studies is needed to avoid the potential risk of misleading conclusions., Scandinavian Journal of Laboratory Animal Sciences, Vol. 15 No. 2 (1988)

Low health literacy is a growing concern affecting up to 20% of the Danish population. Low health literacy is defined by difficulties related to understanding health information and ability to engage with healthcare providers. Research has explored a variety of interventions to address the issue of low literacy. This study describes that educational curricula including lessons and practicing in didactics and health literacy may improve doctors' knowledge and approach towards this group of patients and indicates that healthcare providers generally can benefit from education in health literacy.

In Section 4.3 "Factors Associated with Statin Use in the Oldest Old".

Introduction: In the human capital paradigm, subject to external constraints, a person’s health capital is self-produced. In this producing role they spend time, effort, and financial resources acquiring inputs that either enhance or deplete their health through consuming goods and services relevant[for full text, please go to the a.m. URL], 63. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS)

The evaluation of decision aids and support interventions requires a multi-attribute index which can be calculated for both aid and comparator/s. The Decision Conflict Scale (DCS) is such an index and has been widely used in this context, the recent Cochrane review Decision aids for people facing health treatment or screening decisions reporting its use in 63 of the 105 studies included. However, while the DCS may be a valid measure for the eponymous construct - decision conflict - it lacks both content and construct validity for the evaluation of decision aids. It lacks content validity for this task because of the 3 items which make up its Uncertainty subscale, which penalize an aid that correctly reports the situation is one of decisional equipoise or near equipoise. A 'false clarity' bias in aid presentation is encouraged by being rewarded. In this paper we confirm that the inclusion of the Uncertainty subscale in the DCS has inappropriate empirical consequences for decision aid evaluation. Excluding the Uncertainty items would address this content invalidity, but the DCS would still lack construct validity, since the construct being measured is being treated, and inappropriately psychometrically validated, as a reflective rather than formative one. The component scales (items) of an index for a formative construct need to be preference-weighted, in ethical person-centred care by the individual at the point of decision. We argue that the most appropriate formative construct for use in decision aid evaluation is decision quality, and suggest MyDecisionQuality (MDQ) as the first formative index that can claim to both possess content and construct validity for the measurement of decision quality. However, like all multi-criterial formative metrics, the construct that MDQ measures is constructed by the measure and has no existence independent of it.

Systemic autoimmune rheumatic disorders (SARD) represent important causes of morbidity and mortality in humans. The mechanisms triggering autoimmune responses are complex and involve a network of genetic factors. Mercury-induced autoimmunity (HgIA) in mice is an established model to study the mechanisms of the development of antinuclear antibodies (ANA), which is a hallmark in the diagnosis of SARD. A.SW mice with HgIA show a significantly higher titer of antinucleolar antibodies (ANoA) than the B10.S mice, although both share the same MHC class II (H-2). We applied a genome-wide association study (GWAS) to their Hg-exposed F2 offspring to investigate the non-MHC genes involved in the development of ANoA. Quantitative trait locus (QTL) analysis showed a peak logarithm of odds ratio (LOD) score of 3.05 on chromosome 3. Microsatellites were used for haplotyping, and fine mapping was conducted with next generation sequencing. The candidate genes Bank1 (B-cell scaffold protein with ankyrin repeats 1) and Nfkbl (nuclear factor kappa B subunit 1) were identified by additional QTL analysis. Expression of the Bank1 and Nfkb1 genes and their downstream target genes involved in the intracellular pathway (Tlr9,II6, Tnf) was investigated in mercury-exposed A.SW and B10.S mice by real-time PCR. Bank1 showed significantly lower gene expression in the A.SW strain after Hg-exposure, whereas the B10.S strain showed no significant difference. Nfkb1, Tlr9, II6 and Tnf had significantly higher gene expression in the A.SW strain after Hg-exposure, while the B10.S strain showed no difference. This study supports the roles of Bank1 (produced mainly in B-cells) and Nfkbl (produced in most immune cells) as key regulators of ANoA development in HgIA. Funding Agencies|Swedish Research Council Branch of Medicine; County Council of Ostergotland; Linkoping University

Classification of a continuous risk score into risk levels is common. However, while the absolute risk score is essential, it is arguably unethical to label anyone at 'high, moderate or low risk' of a serious event, simply because management based on a single criterion (e.g. avoiding the target condition) has been determined to be effective or cost-effective at a population level. Legally, mono-criterial risk labeling can inhibit the obtaining of a fully-informed, preference-based consent, since multiple considerations (various benefits and harms) matter to most individuals, not only the single criterion that is the basis of the provided risk category. These ethical and legal challenges can be met by preference-sensitive multi-criteria decision support tools. In this future vision paper, we demonstrate, at a conceptual proof-of-method level, how such decision support can and should be developed without reference to risk-level classifications. The statin decision is used as illustration, without any empirical claims.

In this vision paper we envisage paradigmatic change transforming the health professional from the empowered agent of a dependent patient into the final decision supporter of an empowered person; a person who comes equipped with the preliminary opinion of an apomediative personalised decision support tool and the enhanced health decision literacy it produces. The anomalies in the current paradigm that will produce this change arise from unworkable attempts to combine multicriterial personal preferences and the best available evidence in a medical reasoning model. Multi-Criteria Decision Analysis (MCDA)-based decision support tools provide one mechanism for achieving this synthesis in a transparent way in a specific case whilst, simultaneously, increasing the generic health decision literacy and competencies of both person and clinician. The educational task for both is less than might be expected because of their familiarity, as consumers, with the many comparison websites and magazines for products and services using an informal version of MCDA. The educational task, particularly for the clinician, is primarily one of acknowledging that MCDA is a decision competence that has the potential, not only to enhance decision quality, but also facilitate communication between person and professional, who will now be talking the same decisional language. Experience from developing the MyBoneHealth tool confirms both the feasibility and challenges of delivering a MCDA-based decision support and educational tool.

In this vision paper we envisage paradigmatic change transforming the health professional from the empowered agent of a dependent patient into the final decision supporter of an empowered person; a person who comes equipped with the preliminary opinion of an apomediative personalised decision support tool and the enhanced health decision literacy it produces. The anomalies in the current paradigm that will produce this change arise from unworkable attempts to combine multicriterial personal preferences and the best available evidence in a medical reasoning model. Multi-Criteria Decision Analysis (MCDA)-based decision support tools provide one mechanism for achieving this synthesis in a transparent way in a specific case whilst, simultaneously, increasing the generic health decision literacy and competencies of both person and clinician. The educational task for both is less than might be expected because of their familiarity, as consumers, with the many comparison websites and magazines for products and services using an informal version of MCDA. The educational task, particularly for the clinician, is primarily one of acknowledging that MCDA is a decision competence that has the potential, not only to enhance decision quality, but also facilitate communication between person and professional, who will now be talking the same decisional language. Experience from developing the MyBoneHealth tool confirms both the feasibility and challenges of delivering a MCDA-based decision support and educational tool.

In the health capital model, the main function of health services is not to produce health, but to support the person in their self-production investments. In the health context there are three types of decision support tools, depending on the role of the provider (e.g. clinician) and person. Non-mediative tools are designed to help the clinician decide what is best for the patient. Intermediative Patient Decision Aids are designed to help the clinician and patient decide together, in an encounter, what is best for the patient. Apomediative Personalised Decision Support Tools are designed to help the person decide what is best for themselves, including whether to seek a professional consultation and/or to prepare for, and engage in, an intermediative consultation. Only preference-sensitive apomediative support tools ensure that the key requirements of self-produced health are met, along with legally informed and preference-based consent to any subsequent provider action. The desirable form of apomediative support is a publicly accessible, direct-to-citizen, provider-independent, multi-criteria analysis-based decision support of the sort available in many other areas of self-production. Which (UK), Tænk (Denmark), Choice (Australia) and numerous other comparison magazines and websites provide independent multi-criterial support for decisions on, for example, which food and transport to buy to self-produce nutrition and movement. A personalised decision support tool for the statin decision is provided as illustration: Should I go to my general practitioner and ask for a statin prescription or go to discuss taking statins, in the light of the preliminary opinion of the tool?

The evaluation of decision aids and support interventions requires a multi-attribute index which can be calculated for both aid and comparator/s. The Decision Conflict Scale (DCS) is such an index and has been widely used in this context, the recent Cochrane review Decision aids for people facing health treatment or screening decisions reporting its use in 63 of the 105 studies included. However, while the DCS may be a valid measure for the eponymous construct - decision conflict - it lacks both content and construct validity for the evaluation of decision aids. It lacks content validity for this task because of the 3 items which make up its Uncertainty subscale, which penalize an aid that correctly reports the situation is one of decisional equipoise or near equipoise. A 'false clarity' bias in aid presentation is encouraged by being rewarded. In this paper we confirm that the inclusion of the Uncertainty subscale in the DCS has inappropriate empirical consequences for decision aid evaluation. Excluding the Uncertainty items would address this content invalidity, but the DCS would still lack construct validity, since the construct being measured is being treated, and inappropriately psychometrically validated, as a reflective rather than formative one. The component scales (items) of an index for a formative construct need to be preference-weighted, in ethical person-centred care by the individual at the point of decision. We argue that the most appropriate formative construct for use in decision aid evaluation is decision quality, and suggest MyDecisionQuality (MDQ) as the first formative index that can claim to both possess content and construct validity for the measurement of decision quality. However, like all multi-criterial formative metrics, the construct that MDQ measures is constructed by the measure and has no existence independent of it.

In the health capital model, the main function of health services is not to produce health, but to support the person in their self-production investments. In the health context there are three types of decision support tools, depending on the role of the provider (e.g. clinician) and person. Non-mediative tools are designed to help the clinician decide what is best for the patient. Intermediative Patient Decision Aids are designed to help the clinician and patient decide together, in an encounter, what is best for the patient. Apomediative Personalised Decision Support Tools are designed to help the person decide what is best for themselves, including whether to seek a professional consultation and/or to prepare for, and engage in, an intermediative consultation. Only preference-sensitive apomediative support tools ensure that the key requirements of self-produced health are met, along with legally informed and preference-based consent to any subsequent provider action. The desirable form of apomediative support is a publicly accessible, direct-to-citizen, provider-independent, multi-criteria analysis-based decision support of the sort available in many other areas of self-production. Which (UK), Tænk (Denmark), Choice (Australia) and numerous other comparison magazines and websites provide independent multi-criterial support for decisions on, for example, which food and transport to buy to self-produce nutrition and movement. A personalised decision support tool for the statin decision is provided as illustration: Should I go to my general practitioner and ask for a statin prescription or go to discuss taking statins, in the light of the preliminary opinion of the tool?

Accelerating progress in screening technologies, e.g. genetic testing, means more individuals are facing the stressful decision of whether to request the test. Fully-informed and preference-based consent, as well as ethical practice, requires the full range of benefits and harms from any test or treatment to be identified and assessed from the individual's point of view. For both ethical and legal reasons, we see the decision on whether to undertake a genetic screening test being increasingly seen, in future, as calling for a personalised analysis of the full range of subsequent management options. The conventional dissociation of 'risk assessment' and 'risk management' phases is thereby ruled out. One way of addressing the resulting challenge is through personalised multi-criterial decision support tools. In this vision paper we provide conceptual proof of method of how such an interactive online tool could function. The polygenetic genetic screening decision is used, solely as illustration.

An interactive decision support tool based on Multi-Criteria Decision Analysis (MCDA) can help health professionals integrate the principlist (principle-based) and casuist (case-based) approaches to ethical decision making in both their training and practice. MCDA can incorporate generic ethical principles as criteria; then draw on case-based reasoning as the basis for specifying, in the individual case, the available options, the ratings of each option on each criterion, and the relative weighting of the criteria. This produces a personalised, transparent and decomposable opinion on the merits of each option, as a contribution to enhanced deliberation. As proof of concept and method an exemplar aid adds veracity and confidentiality to beneficence, non-maleficence, autonomy and justice, as the criteria, with case-based reasoning supplying the necessary inputs for the decision of whether a nurse should disclose the poor prognosis of a patient to a close relative of the patient, when asked, on their first encounter.

An interactive decision support tool based on Multi-Criteria Decision Analysis (MCDA) can help health professionals integrate the principlist (principle-based) and casuist (case-based) approaches to ethical decision making in both their training and practice. MCDA can incorporate generic ethical principles as criteria; then draw on case-based reasoning as the basis for specifying, in the individual case, the available options, the ratings of each option on each criterion, and the relative weighting of the criteria. This produces a personalised, transparent and decomposable opinion on the merits of each option, as a contribution to enhanced deliberation. As proof of concept and method an exemplar aid adds veracity and confidentiality to beneficence, non-maleficence, autonomy and justice, as the criteria, with case-based reasoning supplying the necessary inputs for the decision of whether a nurse should disclose the poor prognosis of a patient to a close relative of the patient, when asked, on their first encounter.

Besides diet, house dust has been recognized as an important exposure media for polybrominated diphenyl ethers (PBDEs) [1]. Our previous work showed significant associations between levels in dust and in human plasma, for the congeners BDE-28, BDE-47 and BDE-100 as well as for ΣPBDEtri hexa [2]. Recent results from Sweden indicated that dust was a significant source of exposure for the octa- to decabrominated congeners in particular [3]. Moreover, several novel flame retardants (NFRs) have been detected in dust some of which might be replacement products of PBDEs [4]. Building on these findings, the objectives were to study whether i) the associations observed for plasma also existed for human milk, ii) the PBDE profiles in dust and milk could provide insights into the bioavailability and bioaccumulation of individual congeners, iii) NFRs were measurable in human milk, and iv) infants were exposed to significant amounts of NFRs via breast feeding. PBDEs were detected in all of the 40 milk samples analysed in this study. ΣPBDEtri-hepta ranged from 0.98-45.8 ng/g lw, with a median of 2.26 ng/g lw. The main congener in milk was BDE-153, accounting for 35% of ΣPBDEtri-hepta. This is much higher than in dust collected in the same residences, but comparable to plasma and placenta [2,5]. BDE-99 on the other hand, had clearly lower percentages in human milk than in dust. BDE-209 had a median concentration of 0.64 ng/g lw, which was similar to that of BDE-47 and confirmed that BDE-209 was taken up by humans and, despite its shorter half-life, accumulates to the extent that exposure of infants can occur.As for plasma, PBDE-levels in milk samples were significantly correlated with dust levels (Spearman rank), this was most pronounced for the lower brominated congeners like BDE-28 (p=0.03) and 47 (p=0.006). Large intercorrelation was also observed, e.g. BDE-47 in milk was significantly correlated with most other congeners, though not with BDE-209. In contrast to the plasma results, significant correlation of BDE-99 in milk and dust was also observed (p=0.003). One explanation for this may be the higher detection frequency of BDE-99 in milk compared with plasma (100% vs. 37%).Hexabromocyclododecane and the NFRs bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), 1,2-bis(2,4,6-tribromophenoxy)-ethane (BTBPE), decabromodiphenyl ethane (DBDPE), 2,3-dibromopropyl-2,4,6-tribromophenyl ether (TBP-DBPE) and dechlorane plus (DDC-CO) have been detected in the same dust samples previously analysed for PBDEs and are currently being analysed in the corresponding human milk samples.[1] Stapleon H.M., Eagle S., Sjödin A., Webster T.F. (2012). Serum PBDEs in a North Carolina Toddler Cohort: Associations with handwipes, house dust, and socioeconomic variables. Environ. Health Perspect. 120, 1049-1054. [2] Frederiksen M., Thomsen C., Frøshaug M., Vorkamp K., Thomsen M., Becher G., Knudsen L.E. (2010). Polybrominated diphenyl ethers in paired samples of maternal and umbilical cord blood plasma and associations with house dust in a Danish cohort. Int. J. Hyg. Environ. Health 213, 233-242.[3] Sahlström L.M.O., Sellström U., de Wit C.A., Lignell S., Darnerud P.O. (2015). Estimated intakes of brominated flame retardants via diet and dust compared to internal concentrations in a Swedish mother-toddler cohort. Int. J. Hyg. Environ. Health 218, 422-432.[4] Ali N., Harrad S., Goosey E., Neels H., Covaci A. (2011). “Novel” brominated flame retardants in Belgian and UK indoor dust: Implications for human exposure. Chemosphere 83, 1360-1365.[5] Vorkamp K., Thomsen M., Frederiksen M., Pedersen M., Knudsen L.E. (2011). Polybrominated diphenyl ethers (PBDEs) in the indoor environment and associations with prenatal exposure. Environ. Int. 37, 1-10.

For logistic and practical reasons it is difficult to perform in vitro studies on percutaneous penetration on fresh human skin obtained directly from surgery. Skin samples are therefore often kept frozen until use. The present chapter present the available literature on the topic. Storage of human skin at -20oC causes structural changes in the upper Stratum Corneum observable with image techniques such as multiphoton excitation fluorescence microscopy. The presently available literature does, however, not support that the observed structural damage to the integrity is sufficient to cause a general and significantly increased in vitro percutaneous penetration across human skin stored at -20oC. Use of skin stored at -20oC for in vitro studies on percutaneous penetration therefore seems acceptable as long as the barrier integrity is documented. Storage of human skin at -80oC causes significant structural changes in upper as well as deeper parts of Stratum Corneum. These more severe changes corresponds to significantly increased percutaneous penetration of chemicals applied to skin specimens stored at very low temperatures. Storage of human skin for later use in in vitro studies on percutaneous penetration is therefore not recommended at these low temperatures.

'Symbolic violence' is committed, however well-intentionally, by the imposition of particular conceptualizations of what information, in what form and quality, is needed in order to make an 'informed choice' and hence - by questionable segue - a high quality decision. The social and cultural forms of relevant cognitive capital possessed by those who fail, because of their low general literacy, professionally-set knowledge tests of functional health literacy, are being ignored. Failing to recognise and exploit a particular form of functional decision literacy, in fact leads to symbolic violence being experienced by individuals at any and all levels of general literacy. It leads many to adopt the same range of avoidant and other undesirable strategies within healthcare situations observed in those of low basic literacy. The alternative response we propose exploits the alternative generic decision literacy which comes in the form of the ability to access and use the decision-relevant resources provided for many consumer services and products on comparison websites and magazines. The methodology is the simple form of multi-criteria analysis in which the products' ratings on multiple criteria are combined with criterion weights (supplied by the site) to produce scores and 'best buys' and 'good value for money' verdicts. Our alternative approach extends this approach to healthcare options and permits the incorporation of personal criterion weights in furtherance of person-centred care. Health informaticians, especially those in the decision support field, should build on this widespread generic competence. The fact that it is generic, far from implying context insensitivity, can be seen as a necessary basis for achieving context-sensitivity and sensitivisation at the level of the individual person as they experience a lifelong sequence of healthcare decisions.

Background: Patients' perception of risk and their lifestyle choices are of major importance in the treatment of common chronic diseases. This study reveals determinants for and knowledge about why people accept or reject preventive medical interventions against heart disease. Methods: A representative sample of 40-60-year-old Danish inhabitants was invited to participate in a web-based survey. The respondents were presented with a hypothetical scenario and asked to imagine that they were at an increased risk of heart disease, and subsequently presented with an offer of a preventive medical intervention. The aim was to elicit preference structures when potential patients are presented with different treatment conditions. Results: About one third of the respondents were willing to accept preventive medical treatment. Respondents with personal experience with heart disease were more likely to accept treatment than respondents with family members with heart disease or no prior experience with heart disease. The willingness to accept treatment was similar for both genders, and when adjusting for experience with heart disease, age was not associated with willingness to accept treatment. Socioeconomic status in terms of lower education was positively associated with acceptance. The price of treatment reduced willingness to accept for the lower income groups, whereas it had no effect in the highest income group. Some 57% of respondents who were willing to accept treatment changed their decision following information on potential side effects. Conclusions: In accordance with our pre-study hypothesis, individuals with low income were more sensitive to price than individuals with high income. Thus, if the price of preventive medication increases above certain limits, a substantial proportion of the population may refrain from treatment. More than half of the respondents who were initially willing to accept treatment changed their decision when informed about the presence of potential side effects. This is an important observation in relation to risk communication, since most side effects occur very seldom, and a skewed assessment of treatment efficacy compared to risk of side effects may refrain some patients from treatment. Thus, more research is needed to better allow patients to compare treatment efficacy with risk of side effects in quantitative terms.

Most informatics activity is aimed at reducing unnecessary errors, mistakes and misjudgements at the point of decision, insofar as these arise from inappropriate accessing and processing of data and information. Healthcare professionals use the results of scientific research, when available, and ‘big data’, when rigorously analysed, as inputs into the probability judgements that need to be made in decision making under uncertainty. But these judgements are needed irrespective of the state of ‘the evidence’ and personalised evidence on person/patient-important criteria is very often poor or lacking. This final stage in ‘translation to the bedside’ has received relatively little attention in the medical, nursing, or health informatics literature, until the recent appearance of ‘cognitive informatics’. Positive experience and feed-back from several thousand students who have experienced exercises in assigning probabilities informs our future vision in which better decisions result from healthcare professionals – indeed all of us – having accepted that probability assignment is a skill, with the internal coherence and external correspondence of the probabilities assigned as twin evaluative criteria. As a route to improved correspondence – in the absence of the systematic recording and monitoring of real world judgments that would be the normal pathway to quality improvement – a ‘Prober’ is a set of statements to which the respondent supplies their personal probabilities that a statement is true. They receive the proper Brier score and its decomposition as analytical feedback, along with graphic representations of their discrimination and calibration, the two key components of good correspondence. Provided with estimates of their sensitivity (mean probability true for true statements) and specificity (1 minus mean probability true for false statements) they can visualise themselves as a ‘test’ when making diagnostic and prognostic judgements , thereby being given the cognitive foundation for such reflection in their clinical practice, including ‘reflection in action’. They acknowledge that an appropriate balance of intuition and analysis is required, as in Hammond's Cognitive Continuum, and are made aware of the cognitive and motivated biases that can prevent us knowing ‘how much we know about how much we know’, with its deleterious effect on decision quality. Probability exercises, such as ‘Probers’, are proposed as an enhancement of professional courses and virtual learning environments, such as the TIGER initiative in nursing, through which the competency portfolio of all those seeking to deliver high quality person/patient-centred care can be expanded.

Udgivelsesdato: 24 February

In human risk assessment, bioavailability needs to be considered when relying on in vitro toxicity results. For single chemicals, this quantitative challenge is often handled through a bioavailability factor. For mixtures, however, things are more complicated. Thus, individual constituents may not only interact toxicodynamically and toxicokinetically, but the composition of constituents reaching the target site may also differ from what was present at the site of exposure due to the differences in their bioavailabilities. A recent study concluded on the in vivo potential of Australian tea-tree oil (TTO) to act as an endocrine disruptor based on an in vitro protocol measuring the growth of MCF-7 cells following chemical exposure to TTO. TTO is primarily used topically in humans, and is not a single chemical but is a mixture with some constituents penetrating the skin which others do not. The present study evaluated in an identical in vitro model to what extent TTO and its skin penetrating constituents affected the growth of MCF-7 cells. The estrogenic potency of TTO was confirmed, but none of the bioavailable TTO constituents demonstrated estrogenicity. The present study, therefore, cautions in vitro to in vivo extrapolations from the mixtures of constituents with potentially varying bioavailabilities. Udgivelsesdato: June

ResuméI 2003 blev der gennemført en undersøgelse (miljøprojekt nr. 845) af effekten af de tiltag, der anbefales i Miljøstyrelsens vejledning nr. 7 2000 "Rådgivning af beboere i lettere forurenede områder". Projektet viste en reduktion af eksponeringen efter interventionen i de to let forurenede børnehaver. Dette projekt er en opfølgende undersøgelse i de samme børnehaver 1½ år senere. Projektet viser, at der efter 1½ år stadig er en reduktion i eksponeringen på samme niveau, som kunne konstateres umiddelbart efter interventionen.

Udgivelsesdato: Jun-11 INTRODUCTION: Statistics and a good understanding of numbers are important professional tools for doctors in order to understand and communicate risk estimates. MATERIALS AND METHODS: In this questionnaire survey carried out among 129 specialist trainees the ability to calculate and compare risk values (Relative Risk Reduction, Absolute Risk Reduction, Number Needed to Treat and a combination of these) was examined along with the general understanding of numbers in relation to probabilities. RESULTS: The survey showed that 69% of the participants were able to calculate a risk reduction accurately. Answers from the respondents did not depend on whether information was given as absolute or relative risk reductions. 13% of the participants were able to correctly estimate the risk of a false positive answer in connection with screening. CONCLUSION: The trainee doctors demonstrated a surprisingly poor ability to make basic probability calculations and a poor understanding of screening results. A thorough understanding of risk measures as well as basic probabilities is a prerequisite for good objective patient information. This survey indicates that there is considerable room for improvement in these areas.

Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods: Percutaneous penetration of caffeine (log P -0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded conditions was measured using flow through cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. Results: The maximum flux of caffeine was increased with decreasing skin thickness, although these differences were found to be non-significant. The presence of caffeine in the skin membrane was not altered by skin thickness. Maximum flux and cumulative dose absorbed of testosterone and butoxyethanol (in both finite and infinite doses) were markedly reduced with full thickness (about 1 mm thick) skin compared with split thickness skin (about 0.5 mm). Maximum flux of propoxur (dissolved in 60% ethanol) was clearly higher through skin of 0.71 mm than through skin of 1.36 mm, but no difference was found between 0.56 and 0.71 mm. The proportion of propoxur present in the membrane after 24 h increased significantly over the complete range of thicknesses tested (0.56-1.36 mm). Conclusions: A complex relationship exists between skin thickness, lipophilicity and percutaneous penetration and distribution. This has implications for risk assessment studies and for the validation of models with data from different sources.