Perceptions of Clinical Experience and Scientific Evidence in Medical Decision Making: A Survey of a Stratified Random Sample of Swedish Health Care Professionals.

BACKGROUND: Evidence-based medicine recognizes that clinical expertise gained through experience is essential to good medical practice. However, it is not known what beliefs clinicians hold about how personal clinical experience and scientific knowledge contribute to their clinical decision making and how those beliefs vary between professions, which themselves vary along relevant characteristics, such as their evidence base. DESIGN: We investigate how years in the profession influence health care professionals' beliefs about science and their clinical experience through surveys administered to random samples of Swedish physicians, nurses, occupational therapists, dentists, and dental hygienists. The sampling frame was each profession's most recent occupational registry. RESULTS: Participants (N = 1,627, 46% response rate) viewed science as more important for decision making, more certain, and more systematic than experience. Differences among the professions were greatest for systematicity, where physicians saw the largest gap between the 2 types of knowledge across all levels of professional experience. The effect of years in the profession varied; it had little effect on assessments of importance across all professions but otherwise tended to decrease the difference between assessments of science and experience. Physicians placed the greatest emphasis on science over clinical experience among the 5 professions surveyed. CONCLUSIONS: Health care professions appear to share some attitudes toward professional knowledge, despite the variation in the age of the professions and the scientific knowledge base available to practitioners. Training and policy making about clinical decision making might improve by accounting for the ways in which knowledge is understood across the professions. HIGHLIGHTS: Study participants, representing 5 health care professions-medicine, nursing, occupational therapy, dentistry, and dental hygiene-viewed science as more important for decision making, more certain, and more systematic than their personal clinical experience.Of all the professions represented in the study, physicians saw the greatest differences between the 2 types of knowledge.The effect of years of professional experience varied but tended to be small, attenuating the differences seen between science and clinical experience.

Certainty and systematicity of practice-derived evidence matter for its relative importance in professional decision-making: Survey results on the role of proven experience in Swedish medicine, nursing, OT, dentistry, and dental hygiene.

Background: High-quality healthcare decisions need to balance input from science and clinical practice. When two sources of evidence - such as scientific and practice-derived evidence - are compared, integrated, or need to stand-in for one another, they need to be comparable on similar dimensions. Since 1891, Swedish physicians have been operating under a legal requirement to base their healthcare decisions on science and "proven experience" (approximately clinical expertise), and today all healthcare personnel in Sweden fall under this legal requirement. Objectives: We investigated the dynamics between these two kinds of evidence with respect to importance, systematicity, and certainty by studying Swedish healthcare professionals. Design: Survey to professionals; document studies of political discourse. Method: In this study, a survey was sent to simple random samples of Swedish professionals in medicine, nursing, occupational therapy, dentistry, and dental hygiene, asking about the roles of science and proven experience in medical decision making. Outcome measures were how important, certain, and systematic science and proven experience are for successful medical decision making. Participants: The sampling frame was each profession's most recent occupational registry accessed by the Swedish federal statistical agency. 3500 surveys were distributed. 1626 surveys were returned. 26 participants were removed prior to analysis (exclusion criteria: more than one profession indicated, missing certificate, and mistake in stratum). The final sample consisted of 295 physicians, 300 nurses, 365 occupational therapists, 339 dentists, and 301 hygienists. 162 responses in questions used as variables in the analyses were either uninterpretable or empty; those were replaced with the modal response for a given participant's profession on a given question. Results: In the study, proven experience's perceived importance for clinical decision making is positively correlated with its certainty and systematicity, and an increased certainty and systematicity is positively correlated with a diminished difference in importance between science and proven experience for almost all professions surveyed in this study. Conclusions: Proven experience has an evidentiary role in clinical decision making, and this role depends in part on its certainty and systematicity. Notably, this makes the EBM-based perspective that practice-derived knowledge is primarily of implementation value less plausible.

The epistemic roles of clinical expertise: An empirical study of how Swedish healthcare professionals understand proven experience.

Clinical expertise has since 1891 a Swedish counterpart in proven experience. This study aims to increase our understanding of clinicians' views of their professional expertise, both as a source or body of knowledge and as a skill or quality. We examine how Swedish healthcare personnel view their expertise as captured by the (legally and culturally relevant) Swedish concept of "proven experience," through a survey administered to a simple random sample of Swedish physicians and nurses (2018, n = 560). This study is the first empirical attempt to analyse the notion of proven experience as it is understood by Swedish physicians and nurses. Using statistical techniques for data dimensionality reduction (confirmatory factor analysis and multidimensional scaling), the study provides evidence that the proven experience concept is multidimensional and that a model consisting of three dimensions-for brevity referred to as "test/evidence", "practice", and "being an experienced/competent person"-describes the survey responses well. In addition, our results cannot corroborate the widely held assumption in evidence-based medicine that an important component of clinical expertise consists of experience of patients' preferences.

The Missing Link Between Memory and Reinforcement Learning.

Reinforcement learning systems usually assume that a value function is defined over all states (or state-action pairs) that can immediately give the value of a particular state or action. These values are used by a selection mechanism to decide which action to take. In contrast, when humans and animals make decisions, they collect evidence for different alternatives over time and take action only when sufficient evidence has been accumulated. We have previously developed a model of memory processing that includes semantic, episodic and working memory in a comprehensive architecture. Here, we describe how this memory mechanism can support decision making when the alternatives cannot be evaluated based on immediate sensory information alone. Instead we first imagine, and then evaluate a possible future that will result from choosing one of the alternatives. Here we present an extended model that can be used as a model for decision making that depends on accumulating evidence over time, whether that information comes from the sequential attention to different sensory properties or from internal simulation of the consequences of making a particular choice. We show how the new model explains both simple immediate choices, choices that depend on multiple sensory factors and complicated selections between alternatives that require forward looking simulations based on episodic and semantic memory structures. In this framework, vicarious trial and error is explained as an internal simulation that accumulates evidence for a particular choice. We argue that a system like this forms the "missing link" between more traditional ideas of semantic and episodic memory, and the associative nature of reinforcement learning.

"Science and proven experience": How should the epistemology of medicine inform the regulation of healthcare?

The Swedish medico-legal concept of "science and proven experience" is both legally important and ambiguous. The conceptual uncertainty associated with it can hamper effective assessment of medical evidence in legal proceedings and encourage medical professionals to distrust legal regulation. We examine normative criteria a functioning medico-legal notion should presumably meet, e.g. clarity, acceptability and consistency with existing laws. We also survey healthcare professionals to see how they understand science and proven experience and thus determine the extent to which their understanding meets the normative criteria. The survey suggests that medical professionals feel more certain about "science and proven experience" in the medical context than they do in a legal context. They still have substantial trust in the legal use of the notion, but they do not believe that legal professionals should be allowed to determine the meaning of "science and proven experience" in the legal context. With these results in mind, we argue that the best way to meet the normative criteria and resolve conceptual uncertainty is to specify sub-questions that clarify the notion. We recommend an analytical-deliberative approach that will close the gap between the medical and legal professions' perceptions of how law and medicine relate.

Effects of Anti- Versus Pro-Vaccine Narratives on Responses by Recipients Varying in Numeracy: A Cross-sectional Survey-Based Experiment.

BACKGROUND: To inform their health decisions, patients may seek narratives describing other patients' evaluations of their treatment experiences. Narratives can provide anti-treatment or pro-treatment evaluative meaning that low-numerate patients may especially struggle to derive from statistical information. Here, we examined whether anti-vaccine (v. pro-vaccine) narratives had relatively stronger effects on the perceived informativeness and judged vaccination probabilities reported among recipients with lower (v. higher) numeracy. METHODS: Participants ( n = 1,113) from a nationally representative US internet panel were randomly assigned to an anti-vaccine or pro-vaccine narrative, as presented by a patient discussing a personal experience, a physician discussing a patient's experience, or a physician discussing the experiences of 50 patients. Anti-vaccine narratives described flu experiences of patients who got the flu after getting vaccinated; pro-vaccine narratives described flu experiences of patients who got the flu after not getting vaccinated. Participants indicated their probability of getting vaccinated and rated the informativeness of the narratives. RESULTS: Participants with lower numeracy generally perceived narratives as more informative. By comparison, participants with higher numeracy rated especially anti-vaccine narratives as less informative. Anti-vaccine narratives reduced the judged vaccination probabilities as compared with pro-vaccine narratives, especially among participants with lower numeracy. Mediation analyses suggested that low-numerate individuals' vaccination probabilities were reduced by anti-vaccine narratives-and, to a lesser extent, boosted by pro-vaccine narratives-because they perceived narratives to be more informative. These findings were similar for narratives provided by patients and physicians. CONCLUSIONS: Patients with lower numeracy may rely more on narrative information when making their decisions. These findings have implications for the development of health communications and decision aids.

Looking is buying. How visual attention and choice are affected by consumer preferences and properties of the supermarket shelf.

There is a battle in the supermarket isle, a battle between what the consumer wants and what the retailer and others want her to see, and subsequently to buy. Product packages and displays contain a number of features and attributes tailored to catch consumers' attention. These are what we call external factors comprising the visual saliency, the number of facings, and the placement of each product. But a consumer also brings with her a number of goals and interests related to the products and their attributes. These are important internal factors, including brand preferences, price sensitivity, and dietary inclinations. We fit mobile eye trackers to consumers visiting real-life supermarkets in order to investigate to what extent external and internal factors affect consumers' visual attention and purchases. Both external and internal factors influenced what products consumers looked at, with a strong positive interaction between visual saliency and consumer preferences. Consumers appear to take advantage of visual saliency in their decision making, using their knowledge about products' appearance to guide their visual attention towards those that fit their preferences. When it comes to actual purchases, however, visual attention was by far the most important predictor, even after controlling for all other internal and external factors. In other words, the very act of looking longer or repeatedly at a package, for any reason, makes it more likely that this product will be bought. Visual attention is thus crucial for understanding consumer behaviour, even in the cluttered supermarket environment, but it cannot be captured by measurements of visual saliency alone.

Transient overexpression of DNA adenine methylase enables efficient and mobile genome engineering with reduced off-target effects.

Homologous recombination of single-stranded oligonucleotides is a highly efficient process for introducing precise mutations into the genome of E. coli and other organisms when mismatch repair (MMR) is disabled. This can result in the rapid accumulation of off-target mutations that can mask desired phenotypes, especially when selections need to be employed following the generation of combinatorial libraries. While the use of inducible mutator phenotypes or other MMR evasion tactics have proven useful, reported methods either require non-mobile genetic modifications or costly oligonucleotides that also result in reduced efficiencies of replacement. Therefore a new system was developed, Transient Mutator Multiplex Automated Genome Engineering (TM-MAGE), that solves problems encountered in other methods for oligonucleotide-mediated recombination. TM-MAGE enables nearly equivalent efficiencies of allelic replacement to the use of strains with fully disabled MMR and with an approximately 12- to 33-fold lower off-target mutation rate. Furthermore, growth temperatures are not restricted and a version of the plasmid can be readily removed by sucrose counterselection. TM-MAGE was used to combinatorially reconstruct mutations found in evolved salt-tolerant strains, enabling the identification of causative mutations and isolation of strains with up to 75% increases in growth rate and greatly reduced lag times in 0.6 M NaCl.

Prediction of resistance development against drug combinations by collateral responses to component drugs.

Resistance arises quickly during chemotherapeutic selection and is particularly problematic during long-term treatment regimens such as those for tuberculosis, HIV infections, or cancer. Although drug combination therapy reduces the evolution of drug resistance, drug pairs vary in their ability to do so. Thus, predictive models are needed to rationally design resistance-limiting therapeutic regimens. Using adaptive evolution, we studied the resistance response of the common pathogen Escherichia coli to 5 different single antibiotics and all 10 different antibiotic drug pairs. By analyzing the genomes of all evolved E. coli lineages, we identified the mutational events that drive the differences in drug resistance levels and found that the degree of resistance development against drug combinations can be understood in terms of collateral sensitivity and resistance that occurred during adaptation to the component drugs. Then, using engineered E. coli strains, we confirmed that drug resistance mutations that imposed collateral sensitivity were suppressed in a drug pair growth environment. These results provide a framework for rationally selecting drug combinations that limit resistance evolution.

MODEST: a web-based design tool for oligonucleotide-mediated genome engineering and recombineering.

Recombineering and multiplex automated genome engineering (MAGE) offer the possibility to rapidly modify multiple genomic or plasmid sites at high efficiencies. This enables efficient creation of genetic variants including both single mutants with specifically targeted modifications as well as combinatorial cell libraries. Manual design of oligonucleotides for these approaches can be tedious, time-consuming, and may not be practical for larger projects targeting many genomic sites. At present, the change from a desired phenotype (e.g. altered expression of a specific protein) to a designed MAGE oligo, which confers the corresponding genetic change, is performed manually. To address these challenges, we have developed the MAGE Oligo Design Tool (MODEST). This web-based tool allows designing of MAGE oligos for (i) tuning translation rates by modifying the ribosomal binding site, (ii) generating translational gene knockouts and (iii) introducing other coding or non-coding mutations, including amino acid substitutions, insertions, deletions and point mutations. The tool automatically designs oligos based on desired genotypic or phenotypic changes defined by the user, which can be used for high efficiency recombineering and MAGE. MODEST is available for free and is open to all users at http://modest.biosustain.dtu.dk.

Does causal knowledge help us be faster and more frugal in our decisions?

One challenge that has to be addressed by the fast and frugal heuristics program is how people manage to select, from the abundance of cues that exist in the environment, those to rely on when making decisions. We hypothesize that causal knowledge helps people target particular cues and estimate their validities. This hypothesis was tested in three experiments. Results show that when causal information about some cues was available (Experiment 1), participants preferred to search for these cues first and to base their decisions on them. When allowed to learn cue validities in addition to causal information (Experiment 2), participants also became more frugal (i.e., they searched fewer of the available cues), made more accurate decisions, and were more precise in estimating cue validities than was a control group that did not receive causal information. These results can be attributed to the causal relation between the cues and the criterion, rather than to greater saliency of the causal cues (Experiment 3). Overall, our results support the hypothesis that causal knowledge aids in the learning of cue validities and is treated as a meta-cue for identifying highly valid cues.

LPS-induced bronchoalveolar neutrophilia; effects of salmeterol treatment.

Salmeterol has earlier been reported to have immune modulating effects on Lipopolysaccharide (LPS)-induced neutrophilic inflammation in rodents. The aim of this study was to explore whether 3 weeks regular treatment with inhaled Salmeterol would have a protective effect against neutrophilia, following an LPS inhalation as assessed by bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) in healthy subjects. Fifteen volunteers all underwent bronchoscopies with bronchial wash and BAL on three occasions, each being 3 h after inhalation provocation. The initial inhalation was with saline (dilutant) as a reference and the two following with LPS 50 microg diluted in saline. After the saline inhalation the subjects were randomised to treatment with Salmeterol 50 microg twice daily and placebo in a double-blind double-dummy crossover design. Compared to saline inhalation, the LPS inhalations resulted in a two-fold increase in neutrophils both in BW and BAL, respectively (P < or = 0.01). The neutrophilia was present irrespective of the LPS inhalation was preceded by placebo or Salmeterol. This experimental study could not confirm any modulating effect of Salmeterol on LPS-induced airway neutrophilia.

Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma.

BACKGROUND: The clinical benefit of combining long-acting beta(2)-agonists with inhaled corticosteroids rather than doubling the dose of corticosteroid has been well-documented. However, there are concerns that this might result in a masking of underlying airway inflammation. OBJECTIVE: The aim of this study was to test the hypothesis that the addition of the long-acting beta(2)-agonist salmeterol (SALM) to a low dose of the inhaled corticosteroid fluticasone propionate (FP) has a steroid-sparing effect and does not result in a worsening of bronchial inflammation compared to doubling the dose of inhaled corticosteroid. METHODS: Fifty-six asthmatic subjects, previously not well-controlled on inhaled corticosteroids, were randomized to receive 3 months of treatment with inhaled FP 500 microg twice a day (FP 1000) or FP 200 microg twice a day plus SALM 50 microg twice a day (FP 400 + SALM). Fluticasone propionate 200 microg twice a day served as the control (FP400). Bronchial mucosal biopsy specimens, bronchial washings (BW), and bronchoalveolar lavage were obtained before and after treatment. The primary end points for the study were submucosal mast cell and eosinophil counts. RESULTS: There was a significant improvement in FEV(1) in the FP400 + SALM group compared to both the FP400 and FP1000 groups. This was accompanied by a significant improvement in peak expiratory flow in the FP400 + SALM group in both the morning and evening compared to the FP1000 group. There were no significant between treatment differences in the change in the number of submucosal mast cells or eosinophils. However, in the FP400 + SALM group there was a significant decrease in submucosal mast cells after 12 weeks of treatment. The addition of SALM to FP was not associated with any increases in airway inflammation in the biopsy specimens, bronchoalveolar lavage, or bronchial washings. CONCLUSION: These findings confirm that addition of SALM to FP has clinical benefits but does not mask or exacerbate airway inflammation and suggest that long-acting beta(2)-adrenoceptor agonists might influence mast cell numbers.