Biking and walking are active commuting, which is considered an opportunity to create healthy habits. Objective: The purpose of this study was to determine the main environmental and psychosocial barriers perceived by students, leading to less Active Commuting (AC) to university and to not reaching the Physical Activity (PA) recommendations. Material and Methods: In this cross-sectional study, 1349 university students (637 men and 712 women) were selected. A self-reported questionnaire was applied to assess the mode of commuting, PA level and barriers to the use of the AC. Results: Women presented higher barriers associated with passive commuting than men. The main barriers for women were “involves too much planning” , “It takes too much time”  and “It takes too much physical effort “ . In men, the main barriers were “It takes too much time” , “involves too much planning”  and “too much traffic along the route” . Psychosocial barriers were found in both sexes. Conclusions: Psychosocial and personal barriers were more positively associated with passive commuting than environmental barriers. Interventions at the university are necessary to improve the perception of AC and encourage personal organization to travel more actively. Sedentary lifestyle represents an important risk factor for health, since it participates in the development of chronic non-communicable diseases such as cardiovascular diseases, type 2 diabetes and some types of cancer ,2. SedenThis decrease in PA has not only been related to weight gain and worse psychological well-being , but alsActive commuting , is considered an opportunity to create healthy habits, which improve PA levels, decrease cardiovascular risk ,7 and heThe university stage is a period of transition from adolescence to adulthood, which is characterized by long days of study, a high sitting time , little Studies have shown that the main barriers to PA among university students are related to a lack of time, lack of social support, lack of motivation/enjoyment and economic reasons ,20,21. PIn the same way, the choice of AC, such as walking, can be influenced by several barriers, such as distance and socioeconomic status. It was observed in a study in Spanish university students that those who lived less than 2 km (km) away from the university and those who had a low socioeconomic status used to walk . A shortIn order to follow the World Health Organization (WHO) recommendation that urban planning in cities promote PA and AC through the design of urban spaces , it is iAccording to the evidence presented and the importance of increasing the level of PA in university students by active commuting, it is necessary to get an idea of the mode of commuting in Chilean university students. The objective of this study was to determine the main environmental and psychosocial barriers perceived by students and associated with less AC to university and not reaching the PA recommendations.This cross-sectional study had a non-probabilistic sample  and had a descriptive and correlational analysis in university students from three Chilean regions.n = 265), Health (n = 308), Engineering (n = 716) and Social Sciences (n = 60). More information and inclusion criteria are shown in A total of 1349 students (637 men and 712 women), with an average age of 22.7 ± 5.8 years, from three public  and one private university (Santiago) were selected. They all agreed to participate voluntarily in the study. They were regular students from the first to fifth academic year studying in fields such as Education , university , residence area , live with family and socioeconomic level. To determine socioeconomic level, the Family Affluence Scale (FAS) was used, with the following questions: (1) “Does your family own a car?” , (2) “How many computers does your family own?” , (3) “Do you have your own bedroom for yourself?”  and (4) “Do you have internet access?” . Each answer was summed to obtain the total points. A score was assigned, and participants were classified into three categories regarding the FAS: low (0–3 points), medium (4–5 points) and high (6–7 points) [The sociodemographic characteristics item was sex, age, field of study ( points) .(1) “How do you usually get to university?” and (2) “How do you usually get home from university?”, with a choice of answer options such as walking, bicycle, car, motorcycle, public bus, metro/train and other modes. Walking and bicycle were categorized as “active” modes and other motorized modes as “passive” commuting. The items pertaining to mode of commuting and barriers to the use of AC were used.The mode of commuting to university was defined with the questions: The barriers to AC were indicated, such as “There are no sidewalk or bikeways”; “Bikeways occupied by people who walk”; “There is too much traffic along the route”; “Are dangerous crossing along the way”; “Walking or biking is insecure due to crime”; “Are no places to leave the bicycle safely”; “Streets are dangerous because of the cars”; “I get hot and sweat when I’m walking or biking”; “I’m too loaded to go walking or cycling”, “It is easier to move with car or motorcycle”; “Walk or biking involves too much planning”; “It takes too much time”; “It takes too much physical effort”; “I need the car or the motorcycle to university”. These questions had a categorical like-type response with the alternatives: totally agree = 1; agree = 2; disagree = 3; and strongly disagree = 4 .The International Physical Activity Questionnaire  was used to determine PA levels ,37. The With the authorization of the academic direction of each university and the knowledge of the career directors, the questionnaire was applied in paper format.The application of the questionnaire was carried out from Monday to Friday in the day, evening and executive programs, in the same classroom. The application was carried out in 15–20 min and between the months of April and July 2017. Informed consent was obtained from each student before their participation, which requested the authorization to participate in the research project and explained the objectives and that the collected data were anonymous, private, confidential and for exclusive use in the study.All the participants voluntarily agreed to participate in the study, which was approved by the Ethics Committee of the corresponding university (Code: CCF02052017) and governed by the Declaration of Helsinki 2013 .p < 0.05 were considered. For the analyses, the statistical software IBM SPSS, version 26, was used.The results are presented in frequencies for categorical variables and for continuous variables, in means and standard deviations (M ± SD). To establish the associations between barriers and mode of commuting and barriers and compliance with MVPA, a binary logistic regression was applied to obtain the Odds Ratio (OR) and Confidence Interval (95% CI). Mode of commuting was included in the model as the dependent variable and barriers were included individually as independent variables. The score was also calculated for the barriers, which were grouped into the categories of Environment and Psychosocial. Significant values of “Walk or biking involves too much planning” , “It takes too much time” , “It takes too much physical effort” , were the main barriers. The perception of barriers “The bikeways are occupied by people who walk” , and “I’m too loaded to go walking or cycling” , is associated with the probability of passive commuting increasing by two times. In men, “It takes too much time”  increases the probability of choosing passive commuting four times, while “Walk or biking involves too much planning”  and “There is too much traffic along the route”  increases the probability of passive commuting two times. In general, women presented a greater association between barriers and passive commuting than men.p < 0.05) was positively associated with non-compliance with the recommendations for MVPA in women. In addition, women who reported being “I get hot and sweat when I’m walking or biking”  as a barrier, and men who referred to “It takes too much physical effort”  as a barrier, are less likely to comply with the recommendations for MVPA, since the perception of these barriers is negatively associated with compliance with the recommendations.The main objective was to determine the barriers perceived by students to active commuting to university and the association with physical activity. The main findings were that the passive commuting was the most-used commuting mode to university in Chilean students. The most common barriers associated with passive commuting were “walk or biking involves too much planning” and “it takes too much time” in both sexes.The mode of commuting to university in the current study was mainly non-active commuting (82.2%). Similar results were reported in Spain, where a study of 518 students from two universities revealed that 65.1% of participants engaged in non-active commuting . On the The perception of barriers was divided into “Environmental” and “Psychosocial”, and both variables had a significant association with the choice of commuting to university. In both sexes, the most often perceived barriers were “Walk or biking involves too much planning” and “It takes too much time”. In an Australian study of AC to and from university, travel time was the most important barrier to AC , which iIn our study, it was possible to appreciate that there were more barriers caused by the personal  compared to environmental barriers. A study carried out on university students from Spain showed that both the psychosocial and environmental variables had a significant correlation with AC to the university . AnotherOn the other hand, women showed a greater negative association between AC and the perception of environmental barriers compared to men. In a study on the influence of AC in college students, it was observed that men were more likely to use AC than women, and that, among women, there was a relationship between appearance  and AC . In addiIn our study, it was possible to appreciate that there is a perception of both psychosocial and environmental barriers that would affect the use of bicycles as an active means of transport, with the former being the ones that have the greatest influence. Although it has been described that bicycle use not only depends on the individual mobility behaviors of the user but is also associated with the environment, urban cycling interacts with other modes of travelling, such as public buses, cars, motorcycles and pedestrians . The useA study carried out in Argentina showed a lack of road safety when sharing the road with motorized vehicles as a main barrier to bicycle use . In ChilIn relation to the use of vehicles, an investigation showed that postgraduate students have a greater tendency to use passive modes of commuting (bus or car) due to their work or the possibility of acquiring a vehicle . In ChilThe barriers associated with non-compliance with MVPA are greater in women than in men. In women, in terms of environmental barriers, we find “There are no sidewalk or bikeways” and in the psychosocial barrier is “I get hot and sweat when I’m walking or biking”, compared to men who only have the psychosocial barrier “It takes too much physical effort”. It is important, at this point, to emphasize that the perceived barriers associated with MVPA coincide with AC, that is, a lot of effort and sweating are repeated reasons for women for not doing PA in this study.In the literature, it was found that the barriers to compliance with the MVPA were economic levels, interest in the use of sports facilities, residence, intrapersonal and interpersonal barriers , distancOn the other hand, Sevil et al.  analyzedDespite the numerous significant findings in our study, there were some limitations, including that the student questionnaire was self-reported, and therefore could be subject to bias. On the other hand, the data used were only related to travel between home and university, and cannot be extrapolated to other environments. Our study only recorded the main mode used for commuting, so we did not consider mixed modes. Finally, only four universities were consulted in the research and the geographical characteristics of the three cities where they are located are heterogeneous, and a representative sample per university was not calculated. Therefore, precaution must be taken when generalizing the current results. However, this study makes a significant contribution to the literature on the variety of influences that can affect active commuting. A change in the culture of mobility must begin from within communities and in this sense, university students can be an important target group, especially women, who show a greater negative association between the perception of environmental barriers and AC, as well as with non-compliance with MVPA. Therefore, these findings, in combination with existing research, provide a solid foundation for future studies in this area and the development of policies and programs to improve AC in the university, suggesting that a strong association between the government and university organizations can produce positive results.This study provided important information on perceived barriers to AC and MVPA compliance in Chilean university students. The results of the present study suggest that psychosocial or personal barriers were more positively associated with passive commuting to university than environmental barriers. In other words, aspects based on personal decision to commute actively intervene to a greater extent than the barriers imposed by the environment. Therefore, implementing policies that address the psychosocial factors more, but environmental factors as well, are necessary to increase AC rates, and thus achieve an impact in terms of both health and PA in university students. In addition, our study suggests that it is necessary to target women over men for AC and PA interventions, since women present more barriers and less active commuting. In this way, the measures should not only be applied by the government, but should mainly include universities as the lead actor for the development of educational strategies that promote and increase AC.


The present study examines motives for cycling in the alpine region and focuses on the relative importance of health promotion with respect to other motives. Furthermore, the influences of person-specific characteristics on the rank of the motives are examined, and possibilities for advertising bike tourism based on these motives and characteristics are derived. By applying a quantitative approach, a total of 175 cyclists were surveyed using questionnaires on person-specific characteristics, motives, and their relevance for alpine cycling. Data analysis revealed that health promotion is the most important motive for alpine cycling after fun and action as well as nature experience. Further health-related motives such as stress reduction are also perceived as important. The social component, on the other hand, was given the least priority. The results also showed that person-specific characteristics influence the relative importance of motives. For example, elderly persons and people with children perceive the motive of health promotion as the most important. The study shows that the health-promoting effect of alpine cycling is noticed and may be further encouraged. This study demonstrates that alpine cyclists are a heterogeneous group and that health benefits are perceived by various sub-groups therein. Therefore, any marketing for alpine cycling needs to reflect the diversity of cyclists, and approaches need to be adapted according to the respective target group. Increasing work pressure and performance requirements lead to increased stress, which has a significant role in the development and progression of fatigue as well as physical and mental illness ,2. The rCycling is an outdoor activity that is becoming increasingly diffused in the alpine region, an area with a great potential for health benefits due to its unique and rich nature ,18,19. TThis study covers all forms of cycling in the alpine region, its nature, and environment, which are included in alpine cycling. Due to the various possibilities advertised, it considers different target groups  as well as all forms of cycling such as mountain biking, e-biking, and even road cycling on alpine streets ,26,27,28The motivation to exercise or be physically active has been the subject of numerous investigations ,31,32,33Although studies have already been conducted on specific types of cycling, such as mountain biking, or in non-alpine regions, there are no studies known to the authors regarding cycling motives in the alpine region in particular (except for a master thesis ). TherefThis study applied the self-determination theory (SDT) as a theoretical basis. SDT is frequently used to understand motivation in the fields of sports and exercise ,39,40. IHypothesis 1 (H1).Fun and Action in cycling are the most important motives in alpine cycling.Further, experience of nature as an intrinsic motive is supposed to play a major role in opting for alpine cycling a sporting activity. The unique nature of the alpine region and its experience are an inseparable, essential, and inherent part of alpine cycling, as this activity takes place in the alpine environment and cannot, for example, occur indoors or on the home trainer. However, it could be achieved by means of other activities , which is why we expect it to be second to fun and action.Hypothesis 2 (H2).Nature experience is the second most important intrinsic motivation in alpine cycling.Intensive and fulfilling training is indicated as a possible extrinsic motivation because it is an instrumental reason or result of alpine cycling that can be reached without this specific activity . HoweverHypothesis 3 (H3).Intensive and fulfilling training is the most important extrinsic motive in alpine cycling but ranks after intrinsic aspects.Other extrinsic motives are health promotion as well as related motives , as they, too, can be separated from the activity itself and make it the means to reach a goal. A high degree of autonomy can also be assumed for these motives, as well as the requirement and strengthening of competence. However, we assume increased external determination  and thus less autonomy than for intensive and fulfilling training. We, therefore, derived the following hypothesis:Hypothesis 4 (H4).Health promotion is the second most important extrinsic motive in alpine cycling, also ranking after intrinsic aspects.Since alpine cycling is a sport that can be performed alone, we do not expect social reasons to play a major role but tested them as a control (see Methods section below).Being a popular sport, cycling attracts people with different characteristics. E-bike riders, for example, are particularly interested in social contact, environmental awareness, and the promotion of health . In manyHypothesis 5 (H5).Person-specific characteristics influence the relative importance of motives for alpine cycling.The great potential of cycling tourism is highlighted in many tourism and strategy papers . EspeciaFor this quantitative, correlational, and cross-sectional study , data weThe motives for alpine cycling were measured as single items in the questionnaire, a common strategy in studies on cycling ,35,59,63As personal characteristics, the following items were queried, inspired by previous studies ,34,60,61One hundred eighty-six questionnaires were returned, 11 were excluded due to missing data on motives ,75. TherThe data analysis was performed using frequency analysis, the location measures mean and median, standard deviation, and interquartile range. Furthermore, due to data scaling, correlation analysis was performed using Spearman’s rank-order correlation, and the non-parametric Mann–Whitney U and Kruskal–Wallis H test were used to investigate significant differences . Group cThe most important motive for alpine cycling was “action and fun while cycling”, followed by “nature experience” and “health promotion”. The least important iwa “activity with other people”. p = 0.00 (The motive “intensive and fulfilling training” was significantly less important for people who rode e-bikes (mean rank = 49.73) than for participants who rode non-motorized bikes (mean rank = 95.29), U = 986.5, p = 0.00 . Apart fp = 0.002  than men (mean rank = 96.71), U = 4519.00,  = 0.002 . No otheA higher age correlated significantly positively with the motives “health promotion” (rs = 0.170) and “experience of nature” (rs = 0.066).p = 0,029. The family situation also influenced other motives: the number of children correlated significantly negatively with the “Action and fun while cycling” (rs = −0.205), but showed a significant positive correlation with the motive “Health promotion” (rs = 0.254).The motive “Action and fun while cycling” appeared more important for singles (mean rank = 93.31) than for people in partnerships (mean rank = 91.22) or for married people (mean rank = 70.67), H = 7,051, The majority of people surveyed practiced at least one alternative sport in both summer and winter. In summer, hiking was the most frequently mentioned (119 mentions), before running (97 mentions), mountain tours (75), and climbing (56 mentions). In winter, skiing (108 mentions), ski touring (82 mentions), and snowboarding (37 mentions) were the favored alternative sports before tobogganing (32 mentions) and snowshoeing (19 mentions). The participants did not use the available free-text field in the questionnaire for entering other sports.In the course of the study, motives for alpine cycling were examined.Individuals may have multiple forms of motivation for a particular activity, exhibiting both intrinsic motivation  and extrinsic motivation  ,78. Due All motives studied were rated relatively high for alpine cycling . The highest rating was given to “Action and fun while cycling while cycling”. Hence, the collected data support hypothesis H1. According to the SDT, pleasure can be classified as an inherent satisfaction associated with the activity itself and hence as an intrinsic motivational factor ,79. “Act“Health promotion”, a particularly positive effect of cycling ,21 and e“Health promotion” is strongly connected to “Escaping from everyday life” (the fourth highest) and to “Stress reduction” (the fifth highest). This is in line with a study by Wolf and Seebauer , which s“Health promotion” is also related to “Intensive and fulfilling training”, in addition to “Stress reduction”. In turn, “Stress reduction” is related to “Experience of nature” and, very strongly, to “Escape from everyday life”. The potential of nature to create new experiences, switch off from everyday life, and reduce stress has already been demonstrated in previous work .Although “Activities with other people” was rated the least important, the mean value of the ratings was still above the middle of the seven-point Likert scale. According to the SDT, personal or social connection is an important driver for sustainable motivation ,79 and tRespondents who used an e-bike rated the motive “Intensive and fulfilling training” significantly less important. According to Wolf and Seebauer , the socThere were gender-specific differences in the reasons and motives for riding a bicycle . In the A further influencing factor of the value of the alpine cycling’s motives is the family situation: first, the results showed that for singles, “Action and fun while cycling” were significantly more important than for individuals in partnerships or for married persons. Second, there was a negative correlation with “Action and fun while cycling”. Third, the value of the motive “Health promotion” was positively related to the number of children. A possible explanation for this would be that having children might lead to increased health awareness and desire for health promotion.The data collected show that personal characteristics influence the relative importance of motives for alpine cycling. Therefore, hypothesis H5 was supported.The results showed that, in addition to cycling, other sports are practiced both in summer and in winter. The most frequent mentions regarded sports close to nature and mountain-oriented. From this, it can be deduced that the affinity for nature and alpine sports is also valid outside of cycling and that the preferences and motives collected could also be crucial for other activities and their promotion.This study has some limitations. Due to the cross-sectional design, no interpretations of causal mechanisms can be made based on the data. Since a quantitative approach was employed, deeper content-related insights into the effects and interactions of the various motives were only possible to a limited extent. Moreover, the sample was not randomly chosen to represent a certain population. By using contacts to cycling groups and also by employing an online questionnaire, a bias may have been introduced. While this strategy allows a higher likelihood of reaching people engaged in alpine cycling, former or potential future users might not have been covered, as well as more elderly cyclists without internet access. This was partly alleviated by the fact that alpine cycling is expected to rather attract the younger population.The present study examined the importance of the motive “Health promotion” with regard to other motives and personal characteristics, indicating that alpine cycling is attractive to various target groups for various reasons. This study offers insights into the motives and characteristics on which the promotion of bike tourism in the alpine region can be based. The study’s contribution is threefold: first, it contributes to the literature dealing with health promotion in the context of sports. Second, it expands the knowledge of motivational factors in sports with the application of the SDT. Third, for practitioners, the study provides ideas on how to promote alpine cycling activities based on motivational factors.Due to the health benefits of sports and alpine cycling, in particular, having more people engaging in it presents individual and public health benefits. Moreover, an active lifestyle should be maintained over the life course. Thus, promotional messages for alpine cycling should highlight the health benefits, like the maintenance of vitality and physical aesthetics for more senior users. For younger cyclists, health promotion must be adapted accordingly in service communication. Messages could convey that health is the basis for intensive training and key to reaching specific spots like peaks. The approach to reach young cyclists should also be probably more community-based and use various  media. More traditional channels such as catalog advertising or circulars may still be the most advantageous for older cyclists. However, social media should not be underestimated regarding older cyclists, but the right platforms have to be chosen.Due to the heterogeneity of the cyclists and their motives, the promotion of alpine cycling must be strongly aligned with the respective target groups. In general, action and fun while cycling and the experience of nature are important for every group and should be focused on, also for promoting other sports activities in the region. To attract men, training intensity and the effects of alpine cycling should be highlighted, whereas for families and the elderly, health promotion is more relevant. For the latter, it is important to know that a variety of cycles, including e-bikes, is offered or possible to use. Regarding younger people, mentioning the effects of stress reduction due to alpine cycling seems promising. The social component and the possibility of performing an activity with other people showed the least importance for all groups and should thus not play a prominent role in promoting the activity.Future research should further examine both from a medical and from a tourist point of view how alpine cycling possibilities can and must be designed in order to achieve the best possible effect on public health and the sustainable development of tourism destinations. Based on the presented data, the high affinity with nature and the pleasure derived from the activity could be used to alleviate seasonal differences. For example, summer cycling could be intensively promoted in ski resorts. The well-attended winter season could thereby act as an advertising platform for the summer, promote summer tourism, and contribute to a sustainable destination development.


Talk of mechanisms is ubiquitous in the natural sciences. Interdisciplinary fields such as biochemistry and pharmacy frequently discuss mechanisms with the assistance of diagrams. Such diagrams usually depict entities as structures or boxes and activities or interactions as arrows. While some of these arrows may indicate causal or componential relations, others may represent temporal or operational orders. Importantly, what kind of relation an arrow represents may not only vary with context but also be underdetermined by empirical data. In this manuscript, we investigate how an analysis of pharmacological mechanisms in terms of producing and underlying mechanisms—as discussed in the contemporary philosophy of science—may shed light on these issues. Specifically, we shall argue that while pharmacokinetic mechanisms usually describe causal chains of production, pharmacodynamics tends to focus on mechanisms of action underlying the in vivo effects of a drug. Considering the action of thyroid gland hormones in the human body as a case study, we further demonstrate that pharmacodynamic schemes tend to incorporate entities and interactions on multiple levels. Yet, traditional pharmacodynamic schemes are sketched “flat”, i.e., non-hierarchically. We suggest that transforming flat pharmacodynamic schemes into mechanistic multi-level representations may assist in disentangling the different kinds of mechanisms and relations depicted by arrows in flat schemes. The resulting Baumkuchen model provides a powerful and practical alternative to traditional flat schemes, as it explicates the relevant mechanisms and relations more clearly. On a more general note, our discussion demonstrates how pharmacology and related disciplines may benefit from applying concepts from the new mechanist philosophy to guide the interpretation of scientific diagrams. Natural sciences in general, and biochemistry and pharmacy in particular, tend to investigate complex actions and interactions of and between entities, such as small-molecule compounds, biopolymers, cells and organisms. Some of these interactions can be assigned to the “Molecular Level”, where atoms, molecules, light and other forces interact. Others subsequently transcend to “higher levels” or scales, such as entire organisms in biology and medicine. At the highest levels, we even find interactions between organisms or between organisms and their environment as studied by psychology and sociology.  complex diagrams in pharmacology, such as the one shown above, superimpose representations of different types of mechanisms onto one another, and that (ii) arrows in these diagrams represent a number of different relations ,6. IndeeRecent discussions about explanations in the philosophy of science capitalize on the potential of mechanisms to provide integrated multi-level explanations ,7,8. AccA mechanism for a phenomenon consists of entities (or parts) whose activities and interactions are organized such that they are responsible for the phenomenon to be explained.This unifying characterisation usefully communicates the central tenets of the new mechanist philosophy. Still, it leaves important issues underspecified. For instance, there is considerable discussion about what exactly “phenomena” are ,12,13. Fkinds of mechanisms. While some may be inclined to read this as a metaphysical thesis, we prefer to consider this as a triad of three kinds of mechanistic explanations. If this is correct, being “responsible for” can take at least three different forms in mechanistic explanations. Firstly, it can refer to a causal relation where the phenomenon is the effect of the preceding mechanism’s operation. Secondly, “being responsible for” can denote a constitutive relation where the phenomenon is the overall behaviour of the mechanism . Lastly, it can describe some set of regulatory relations which keep a certain state stable or continuous process going. Accordingly, the mechanisms which produce, underlie, or maintain their phenomena are suited to explain different kinds of phenomena, i.e., to explain how a product or an end-result is generated, scientists will usually search for a mechanism which produced it; to explain a process, they will typically search for the mechanism underlying it; and to explain how a system’s stable state or continuous behaviour is maintained, they search for the mechanism maintaining it [for a specific phenomenon.In their book on mechanism discovery, Craver and Darden suggest that there are three different kinds of mechanisms : mechaniining it . The ideining it ,17,18. BOur project in this manuscript is to examine how different kinds of mechanistic explanations act in concert in pharmacology. For the current purposes, we shall focus on producing and underlying mechanisms. An elaborate discussion of maintaining mechanisms demands for a project of its own.The distinction between producing and underlying mechanisms mirrors the familiar distinctions between etiological and constitutive explanations . Still, Firstly, a producing mechanism may be located within an underlying mechanism see . In studSecondly, each step in the causal sequence of a producing mechanism may be spelled out further by identifying the underlying mechanisms at each stage, the top circles shaded in green in The major difference between these scenarios is how the information is integrated into a coherent picture. The first scenario provides an analysis of some of the causally productive processes within a mechanism recognized to underlie a phenomenon . By contIn Combining insights about producing and underlying mechanisms enables researchers to construct nested multi-level mechanistic explanations, as illustrated in Baumkuchen models, inspired by the layered structure of the famous Austrian Baumkuchen, rather than multi-level mechanisms. As mentioned before, choosing a new term highlights that we do not commit to the idea that the interlevel relations in our diagrams will strictly conform to mechanist definitions of interlevel relations as local part-whole relations [This is the basic rationale we adopt in the discussion which follows. Our starting point is to recognize that pharmacokinetic mechanisms usually describe causal chains of production, while pharmacodynamics tend to focus on mechanisms of action underlying the in vivo effects of a drug. As such pharmacodynamic schemes cross different levels of investigation and, they should be represented by a multi-level diagram incorporating productive aspects at various levels, similar to the one in elations . We aim box and arrow” diagrams. Note that the pharmaceutical notion of MoAs differs from the one employed in other sciences. In systems biology, for instance, a mechanism typically describes the interactions between different parts and processes within a larger overall system. In chemistry, reaction mechanisms may refer to abstract models or hypothetical constructs proposed to explain or predict certain processes or products. Here, we notice that mechanisms may feature different kinds of explananda; still, the commitment to realism is stronger in the case of pharmacology MoAs than those in chemistry.Pharmacology is the science which focuses on studying the interactions between substances, notably drugs, and living systems . This scpharmacokinetics, MoAs describe how a drug enters the body and how it is subsequently distributed, metabolized and excreted, with a focus on the drug itself. Such mechanisms are usually analysed as causal chains of mechanisms and may also be represented by mathematical formulae. They describe the journey and transformation of the drug itself. Spironolactone, for instance, is a potassium sparing diuretic, hence has its indications in handling hypertension and chronic heart failure. Spironolactone reaches its peak plasma concentration after 2.6–4.3 h. It is circulated in the body, with 90% bound to plasma proteins, and undergoes extensive liver metabolism and is then excreted in urine and bile [In and bile ,21.Pharmacodynamics, by contrast, employs MoAs, which are predominantly underlying ones, . In its glossary for chemists, the International Union of Pure and Applied Chemistry (IUPAC) defines pharmacodynamics as the “study of pharmacological actions on living systems, including the reactions with and binding to cell constituents, and the biochemical and physiological consequences of these actions.” [ctions.”  In otherctions.” ,21,23. PIn summary, pharmacokinetic MoAs describe productive chains often employing mathematical formulae, e.g., about half-life, whereas pharmacodynamic MoAs describe processes which underlie higher, e.g., organism-level physiological effects of the drug in question. Such higher-level effects are based on “reactions with and binding to cell constituents”, i.e., processes on a lower level responsible for the MoA’s operation. As we shall demonstrate below , analysiThis brief exposition begins the discussion we shall elaborate on in the following sections: pharmacologists investigate mechanisms at various different levels. Additionally, despite the fact that the common-place representation for MoAs is non-hierarchical, we already had a glimpse at the multi-level picture hidden underneath. The key to transforming flat pharmacological diagrams to multi-level ones will be, as we shall see in the next section, to recognise that the arrows contained in traditional “box and arrow” diagrams represent different kinds of “being responsible for” relations. Once we disentangle these different arrows, a multi-level representation of pharmacological MoAs as consisting of a variety of inter-connected producing and underlying mechanisms results almost naturally.Common pharmacological schemes and diagrams condense high complexity in two-dimensional images containing lots of boxes and arrows. While boxes represent mechanistic components, and arrows are suggestive of causal relations, this simplified reading is often misleading. To illustrate this point, we now consider the biosynthesis and subsequent activity of the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in the healthy human thyroid gland. This scheme is depicted in The most common arrow found in pharmacological diagrams is the straight arrow. It occurs in lots of variations: unidirectional, bidirectional, as a solid line  or as a block arrow . Such arrows suggest some kind of causality and often carry additional information above, below, or inside. More precisely, the arrow implicitly tells us that products produced within the thyroid gland circulate to the muscles, where they influence or control muscle mass. As T3 and T4 are the messengers between these two organs, they should be correctly placed inside the arrow or next to it. Interestingly, the interpretation of this type of arrow is in line with the notion of “systems” in biology, as mentioned earlier in In chemistry, the straight black arrow differs as it connects educts of a chemical reaction with the respective products. This arrow describes a causal relation between chemical compounds, either unidirectional or in equilibrium, and connects chemical symbols which usually—although not always—stand for elements, ions, molecules, etc. In In addition to simple straight arrows, there are also arrows pointing at products which may be expected on a theoretical basis. For a number of reasons, though, the anticipated product(s) may only be obtained in the laboratory. The “crossed out” straight arrow highlights that the substance in question is not formed under the reaction conditions employed. Such a special case of a “crossed out” straight, producing arrow is tagged with 3 in It should also be noted that some of the straight arrows in Interestingly, the chemical reaction sequence in As we dig deeper, another kind of arrow appears in As we shall explain in the following section, the mechanism which underlies the underlying mechanism of the chemical reaction is considered to reside at the lowest level in the case at hand. It is important to note, though, that this reflects a pragmatic choice of the “bottoming-out” point for the discipline of pharmacy rather than a metaphysical commitment; we find it applied in many illustrations in the field chemical processes which actually cross different levels of investigation. In order to reveal—at least some of—the ambiguities which may result from such a collapse of a multi-level hierarchy into flat schemes, we need to (a) distinguish between different levels or layers of analysis , (b) distinguish between different kinds of mechanisms , and (c) disambiguate between different kinds of arrows and which kinds of “being responsible for” relations they depict. If this task is taken seriously, a multi-layer Baumkuchen model can be constructed out of non-hierarchical pharmacological diagrams. Such a representation can be achieved by drawing on our discussion above to provide a practical and powerful tool to represent MoAs in pharmacology.What does this look like for our case study? As we look closer at the different layers within the Baumkuchen model in These constructs, together with reaction intermediates, form the second level of the Baumkuchen, which is home to the underlying reaction mechanism explaining the chemical reaction itself, and including the intermediate MIT. This chemical reaction, in our case proceeding from tyrosine and iodine to T3 and T4, resides on the third level, which we have referred to as “Chemistry Level” before. Curiously, in physiology, the chemical reaction itself is often considered as “underlying” and tends to be referred to as the “mechanism of biological action” or “mode of action”. Interestingly, the choice of the bottom level may differ according to discipline. While a chemist considers a chemical reaction to be on top of the cone, towering above the reaction mechanism and resonance levels, the physiologist, in contrast, will build the cone on the chemical reaction itself. Subsequently, the pharmacological mechanistic analysis of how thyroid gland hormones act in the human body bottoms out at the transition from tyrosine and iodine to T3 and T4. This ignores the fact that the chemical conversion process in question can also be considered as a mechanism on its own. The subsequent layers of the cake are rich in biochemistry. Here, chemical interactions, for instance of T3 and T4 with their respective receptors, result in physiological changes, such as muscle growth. Higher up, this layer of physiological processes provides the underlying mechanism(s) for health and disease, in more general terms.The Baumkuchen model does have several advantages over traditional non-hierarchical models. Most importantly perhaps, it is richer in content and disambiguates different dependency relations based on careful analysis. It allows researchers to zoom into individual layers and to focus in on specific aspects of the overall state of affairs. Still, it is far from perfect: several “unidentified” arrows and relations remain, not all entities and activities can be clearly located at specific levels, it is not clear what adequate levels are in any given case, etc. Besides, we have not discussed how to incorporate regulatory maintaining mechanisms into our Baumkuchen picture. While a detailed discussion of this issue asks for a separate publication, we guess that—at least in principle—it should be possible to analyse maintaining mechanisms as continuously operating underlying or producing mechanisms or a combination thereof (see  for discWe have demonstrated that careful analysis of ambiguous “flat” pharmacological “box and arrow” schemes may benefit all parties involved. Importing the concepts of producing and underlying mechanisms from new mechanical philosophy of science to pharmacology has allowed us to propose a new type of diagram for pharmacologists to employ in practice. The Baumkuchen model provides a powerful alternative to traditional pharmacological diagrams. It has all the representational resources of traditional “flat” diagrams whilst adding information about interlevel relations and disambiguating between the different relations represented by arrows in traditional “box and arrow” schemes. Importantly, the Baumkuchen model is easy to construct with familiar tools and resources and subsequently may be expanded to interactive virtual electronic versions of such multi-layered schemes. This is indeed the case with conventional flat diagrams in the pharmacology textbooks utilized in this manuscript ,23. NowaThat said, let us remind our readers that we are not aiming to draw any strong metaphysical conclusions. Whilst we do share a certain realist commitment, we are certainly aware that empirical evidence may underdetermine which Baumkuchen model is actually correct or most realistic. Still, even hypothetical or inaccurate multi-level models can progress research. At the very least, they may offer hypotheses as to how pharmacological mechanisms work together to give rise to complex phenomena, such as the action of thyroid gland hormones in the human body. As such, they potentially offer deeper insights for pharmacology research than traditional “box and arrow” schemes can possibly offer. Therefore, we submit that constructing multi-level Baumkuchen models will help pharmacologists to gain deeper insights into how various MoAs are linked and also to guide future research.


To explore and describe how healthcare policymakers and healthcare practitioners from different levels of Swedish healthcare perceived the everyday practice of putting national policies to contain antibiotic resistance into effect.A strategic sample of four healthcare policymakers, three healthcare practitioners working in hospital care, and six working in primary care were recruited and interviewed in person. A manifest and latent content analysis was carried out on the transcribed interview data.Analysis revealed how the everyday practice of containing antibiotic resistance in different healthcare levels could be perceived as successful, difficult, or a dilemma. The informants’ perceptions are presented in three categories which describe first; informants’ perceptions of antibiotic use and antibiotic resistance in Sweden; secondly, informants’ perceptions of definable efforts in containing antibiotic resistance in Sweden, most notably responsible use of antibiotics, prevention of infection, improving public knowledge of antibiotic resistance, and international collaboration; and thirdly, informants’ perceptions of problem areas in containing antibiotic resistance in Sweden, such as behavior, attitudes and knowledge among healthcare practitioners and the public, work environment, and resources. Reflection on the underlying meaning of these perceptions led to identification of the latent theme, labelled “A sense of relative success, and many challenges yet to overcome”.This study has given in-depth insight into how a group of healthcare policymakers and practitioners perceived the everyday practice of containing antibiotic resistance, and revealed their perceptions of successful efforts to combat antibiotic resistance so far. It has identified problem areas in different healthcare levels, bringing to light challenges yet to overcome, and areas to focus on in future policies, most notably more emphasis on attitude and behavior change, and increasing awareness of antibiotic resistance among both healthcare practitioners and patients. Antibiotic resistance (AR) is recognized as a significant threat to global health in modern times . AlthougEfforts to combat antibiotic resistance are being driven by global organizations, such as the World Health Organization (WHO), World Organization for Animal Health (OIE), United Nations Food and Agriculture Organization (FAO), as well as health communities in Europe, North America, and Australia . In receIn Sweden, systematic initiatives to contain antibiotic resistance beginning in the mid-1990’s have contributed to the present favorable situation of having limited antibiotic resistance and low antibiotic consumption . One notStrategies to combat antibiotic resistance adopted by the Swedish government in 2016 included “continuous collection of data on the occurrence of resistant bacteria and use of antibiotics”, “continuous strong preventive measure to minimize the spread of multi-resistant bacteria”, “responsible use of antibiotics, ‘”improved awareness and understanding in society about antibiotic resistance”, “clear systems and structures for collaboration”  has become lot better if you compare to how it was in the 80’s and 90’s. We’ve seen that the use of antibiotics has been halved, at least for children, compared to the 90’s. And we haven’t seen any increase in complications…that patients suffer in any way. So antibiotic use in Sweden is pretty good, in any case compared to other countries” (PC Physician H2).All informants shared the opinion that the use of antibiotics in Sweden was much better now than 20, 30 years ago, and that Sweden is one of the furthest in restrictive antibiotic use compared to other countries. “We are generally careful with antibiotics ….we don’t prescribe them if they are not necessary… we start with simple measures for fever, colds, and so on, so not using antibiotics unnecessarily is always in the back of our minds.” (PC physician H10) This quotation is an example of how one informant understood the need for healthcare practitioners to be restrictive in prescribing antibiotics and the need for people to refrain from using antibiotics, if possible. “Every antibiotic cure upsets the bacterial balance in the stomach even more…and can result in resistant bacteria attaching themselves …so every antibiotic cure can disturb intestinal flora for almost a year…you can say…and then it is easier during that year to be infected by resistant bacteria…so that’s why you really have to evaluate every individual antibiotic cure…is it really necessary?” .Still, you can wonder if it really is correct that one of three patients are given a dose of antibiotics, at least once during their hospital stay. So…antibiotics are being overused, even in hospitals.” .Even so, there was an opinion that antibiotics were still being used unnecessarily in Sweden.”“I’ve worked in Ethiopia for example, where amoxicillin was doled out …to children. But there I thought the same way, play it safe, there you have all the more reason to do so …children are undernourished and sick…but yes, generally speaking I believe many received antibiotics without needing it” .Among healthcare practitioner informants there was a general perception that antibiotics were being misused in other countries. Their opinions in this matter were based on personal experience and observations when working abroad, or from scientific and specialized press, and media coverage. Informants’ awareness of the use of antibiotics in animal food production was limited, and also based on media coverage. Very few informants were aware of, or had much knowledge of environmental effects of antibiotics and other drugs.“I think a lot about all the plastic surgery operations being carried out abroad….where they are so much cheaper…so people travel abroad, have a lot of operations, and then come back with MRSA bacteria. And maybe they don’t say anything when they visit a hospital, which spreads infection even more” (PC nurse H8).Policymaking informants had the perception that people felt ‘relatively safe’ in Sweden regarding antibiotic resistance. There was a belief that food in Sweden was produced under good conditions, and therefore was there no need to worry about resistant bacteria or antibiotics in food. Instead, there was a belief that antibiotic resistance was imported into Sweden, via travel, picking up bacteria during hospital stays for cheaper medical care in other countries, eating contaminated food, abroad or at home. “An ordinary doctor comes upon it [antibiotic resistance] two, three, four times a year, or something like that…a urinary tract infection that doesn’t get better, and results in pyelonephritis.” (PC physician H2) Antibiotic resistance was also not a real issue in dental care. “It’s not as if….resistant bacteria cause oral infections, that’s not the way it is….no.” (Policymaker H12) However, according to policymaking informants, resistant bacteria have been involved in outbreaks of infection in hospitals. “Resistant bacteria, we have had outbreaks…we have had big ones involving many hospitals…Vancomycin resistant enterococci for example. And then infection spread in neonatal wards with serious consequences. So the topic is highly relevant in Sweden as well” (Policymaker H4).There was an impression among the informants that antibiotic resistance was still a small problem in primary care. If and when it was suspected, patients were treated according to specific routines, or referred to hospitals. “Imagine a mountain side with water running into a lake containing all the antibiotic resistance. We [Sweden] are a tiny stream, and then you have a giant rapid, a glacial rapid, coming from the rest of the world, Of course it doesn’t matter what we do.. it won’t be noticeable…our efforts almost make no difference in the overall context” (Policymaker H.7).All the informants were aware of the serious consequences of antibiotic resistance, that, in the end, it might not be possible to treat infections with antibiotics at all, and people could die. Policymaking informants had the most extensive knowledge of antibiotic resistance. They felt that people did not really understand the paralyzing breadth of antibiotic resistance, and the death and suffering it could lead to. One policymaker noted that mankind did not react to slow scenarios, where it was possible to adapt slowly, and compared the threat of antibiotic resistance to climate change, something not yet experienced as a direct threat. Antibiotic resistance was a ticking bomb, a threat today, and a potentially greater threat in the future. And the future, according to the following policymaker, was very uncertain. This category presents informants’ spontaneous examples of efforts where they felt they had been successful in their work to contain antibiotic resistance.“These [Strama] doctors have been very good at coming out and informing and putting pressure on our doctors….like…to reduce… and make the right diagnosis ….most importantly the right diagnosis….certain diagnoses do not need antibiotics” (PC nurse H11).One policymaking informant described how work to decrease the use of antibiotics had first focused on primary care, since antibiotics appeared to be overused in many PC clinics. And it was perceived that these efforts had been successful. All the informants were very aware of Strama’s role in facilitating responsible antibiotic use and increasing awareness of antibiotic resistance in primary care. Examples included how PC clinics were regularly visited by healthcare professionals working with Strama, who informed about antibiotics and infection treatment. “In spite of all the alarm reports, I believe, and if you ask my colleagues, that the use of antibiotics in Sweden is going in the right direction That is what I believe and how I feel, and my colleagues feel the same way. On the other hand I don’t know how that is affecting antibiotic resistance, but we are much more rational now than 15 years ago” (PC physician H1).Recommendations for correct antibiotic use in dentistry had been revised in 2014, in collaboration with Strama; telenurses used telephone advice guidelines to advise callers, which also followed Strama guidelines on antibiotic use; Strama regularly followed up antibiotic use in primary care and public health dental clinics; hospitals received data on their total antibiotic use from Strama every 3 months, but how they used this information varied. Patients seek acute dental treatment, for swelling, but most of all for pain…toothache. And antibiotics are not a way to treat toothache…so many times it is enough with local treatment combined with pain relief” (Policymaker H12).There was a general opinion about primary care, that it was easier to be more restrictive when prescribing antibiotics, since infections in primary care require a completely different spectrum of antibiotics compared to infections treated in hospitals. It was a question of choosing where to draw the line, prescribe less antibiotics, only when necessary, and less broad spectrum antibiotics. A policymaking informant had similar thoughts about dentists. ““The chances of being infected with resistant bacteria in the subway is almost zero….there is little risk of being infected in outpatient clinics, but it can be a reality in a hospital.” (PC physician H2) According to one hospital specialist informant, strategic efforts on part of hospital management had led to better hygiene routines in hospitals, which were followed a lot better now compared to 15 years ago.Then we have a hygiene nurse in charge of educating personnel…different personnel categories, from assistant nurses, ward aids, paramedics, nurses, to department heads are expected to register…. and who also is responsible for hygiene rounds, to check up on how we work with basicl hygiene routines (PC nurse H5).Primary care had strict routines regarding clothes and hand hygiene, to prevent the spread of infection, not just resistant bacteria. Hygiene routines in dental clinics followed national guidelines. In nursing care of the elderly a special hygiene nurse had hygiene rounds to control how staff followed basal hygiene routines. Newly hired and temporary staff was required to learn basal hygiene routines, and even sign a document where they agreed to work according to these rules.”All PC clinics had somebody responsible for infection control. One PC physician informant was part of a Strama network comprised of other doctors, disease control specialists, and nurses from other PC clinics in the region. Their network disease control meetings covered many areas, for example chlamydia, HIV, hygiene, as well as antibiotic resistance. One PC nurse informant working in municipal elderly care described her role in being responsible for keeping statistics on infections in elderly care, and how she was always informed if new patients coming from hospitals were carrying resistant bacteria.”You try to explain about resistance…I say [to the patient] ‘ imagine if you really get sick in the future…and need antibiotics…and they don’t help…how would you feel?’… and then I talk a lot about intestinal flora….I usually say you may win a few days….but think about how you are destroying your stomach and intestines…..it takes many months to build up your normal intestinal flora again” (PC nurse H11).One PC physician informant felt it was important to make patients understand why antibiotics were not always necessary. A PC nurse informant, on the other hand, thought that doctors were often stressed, and had little time to inform patients properly. According to this informant, patients received better information from nurses than doctors, who were often stressed, with little time to inform patients properly.“I think the media has played a very important role….describing the problem [antibiotic resistance] … reporting successes and statistics and such…it has been very engaged and ….has understood the importance. There are many medical journalists who have understood the importance through the years and this has resulted in general reporters joining in. That’s how it sunk in.…these newspapers are read by decision makers, doctors, veterinarians, and the general public.” (Policymaker H3) People were beginning to understand the negative effects for self and society, many even were trying to avoid taking antibiotics, if possible. People who insisted on antibiotic treatment still existed, but were fewer in number, and often badly informed.All the informants commented on the media’s role in changing the publics’ expectations regarding antibiotics. “They [EU countries] are very interested…it’s not as if they just sit there because they have to…but they are very engaged in what needs to be done and come with suggestions …so it is very promising.” (Policymaker H4) And, there was a perception that success of Swedish efforts in antibiotic resistance work so far had resulted in an interest in Sweden as a role model.Policymaking informants described their collaboration with animal and environment health sectors in Sweden, and their involvement in global efforts to contain antibiotic resistance. Examples included representing Sweden in projects together with other EU countries, such as monitoring antibiotic resistance and healthcare associated infections, and regular meetings to create national action plans for antibiotic resistance work. People want to keep their eyes closed to the problem of antibiotic resistance, there are too many economical consequences” (Policymaker H7).The policymaking informants also had a good understanding of the realities of global collaboration, how antibiotic resistance work was affected if countries had to deal with lack of water, climate change, natural disasters, and limited resources. For example, Bric countries  wanted the same healthcare outcomes as industrialized countries, but did not have economical or hygienic conditions, and compensated by using a lot of AB in healthcare and food production. It was very hard to stop the actions of these countries. “This category gives insight into informants’ perceptions of problems they faced in their work to contain antibiotic resistance.“Higher antibiotic prescribing in some primary care clinics does not always mean sicker patients, but maybe a different culture” (PC physician H10).In primary care, as noted by PC informants, there were differences in how physicians trained abroad looked upon antibiotics compared to physicians trained in Sweden. There was an impression that some foreign physicians in Sweden still seemed to work according to the antibiotic culture in their homeland, that of treating common infections with antibiotics. As a result, antibiotics appeared to be used a lot in areas with high concentration of immigrants, and in PC clinics with many foreign physicians. So the difficulty, I believe, is when you stand there at night…from my perspective….in the darkness of night and do not really know how sick a child is….so you choose maybe a broader antibiotic …or antibiotics when you don’t really need them.”  As noted by hospital specialist physician informants, antibiotics could be overused to some extent in orthopedic hospital care, as it could be hard to diagnose if or when an infection did not require antibiotics. Furthermore, they noted that regular follow-ups on antibiotic use were not always carried out in orthopedic, or pediatric hospital clinics.Decreasing the use of antibiotics in hospitals was not always straightforward. For example, some specialist physicians felt uncomfortable about treating seriously ill hospital patients with narrow spectrum antibiotics. In pediatrics, the practice was to start with broad spectrum antibiotics, before resistance testing, since pediatric specialists could fear the serious consequences of infection in small children.”Sometimes you can be forced to prescribe something only because your superior thinks you should and because there are many doctors involved in the process.” (Policymaker H7) The policymaking informants were also aware that some doctors were not interested in changing their ways.”Thinking Sweden is good when it comes to antibiotic resistance work can lead to arrogance among healthcare professionals, that we are done, and do not need to bother anymore” (Policymaker H3).Policymaking informants had the opinion that the mindset of ‘it never hurts to prescribe antibiotics’ needed to be changed, and questioning if antibiotics were necessary in treatment planning should be put into practice in hospitals. They realized how difficult this could be for some younger doctors.”Most of the informants had limited knowledge of antibiotic work internationally, in animal food production, and in the environment. Very few were aware of the One Health concept. One PC physician informant thought that One Health was not important to physicians in local PC clinics, and that One Health should work from a higher level, coordinating animal and human sectors, and exerting pressure internationally. This informant would also have liked to see real evidence that antibiotics in animal food-production contribute to antibiotic resistance in humans.“Many parents are very convinced and well read, but base their opinions on wrong sources” .One policymaking informant observed that vaccinations to prevent viral infections that have bacterial consequences could result in less antibiotic use, and, although rare, it was unfortunate that some children were not being vaccinated today, since these children could end up in emergency pediatric clinics. They say … doctors don’t have the time to listen to us, or they didn’t listen, or even inspect my throat, we just got a prescription” (PC nurse H8).PC physician informants were aware that some patients travelled abroad, stocked up on antibiotics to sell to friends when home in Sweden, or took only half their antibiotic cure, to save for the next times. They understood that many of these patients did not believe they would get better without antibiotics. Patients could also demand antibiotic prescriptions from their dentists before going abroad. One PC nurse informant working in telephone advice services described feelings of anger when patients called in and admitted they had bought antibiotics abroad. It was difficult to convince some people to begin with over-the-counter medicines, and try to endure, especially if they were parents of small children with fever. This informant had observed people’s concerns about antibiotics, which may be why they called Sweden’s national telephone advice services. “If you are going to have the opportunity to admit a patient, to wait and see what happens before setting in antibiotics, you need an understanding environment, colleagues, a bed,…and you need more time” .Informants in both hospital and primary care remarked on their stressful work environment, there was just not enough time to convince and inform patients about antibiotic use and antibiotic resistance. Physician informants in both primary care and hospitals said they ended up prescribing antibiotics when stressed and felt the need to act. Furthermore, stress, short hospital stays, lack of beds could result in choosing broad spectrum antibiotics instead of narrow spectrum antibiotics, and which also increased the risk of infection spread in hospitals. And, a very high turnover of hospital staff made antibiotic resistance work, and education of staff difficult. There was a shared opinion that hospital management should be more open and sensitive to the problem of antibiotic resistance, and should take larger responsibility for antibiotic use and antibiotic resistance issues. “It is quite fascinating that everybody says this [antibiotic resistance] is one of the biggest problems we have, a future problem from a global perspective. Still there is no money. The Swedish Research Council abstained from targeting money for antibiotic resistance research….it was targeted for infections, yes, and now we have stronger focus on virus research and such and I don’t think there is much left over for antibiotic resistance research.” (Policymaker H7) International cooperation, according to another policymaking informant, was one way that Sweden, as a role model, could spread knowledge about AR work, and limited resources made it hard to respond to international demands for this knowledge.Resources seemed to be an area of concern for most informants, including even some policymaking informants. It was hard to know if there were enough resources for antibiotic resistance work, funding of campaigns, research, etc.”In summary, insight into perspectives, and from different healthcare levels, has revealed how the daily practice of containing antibiotic resistance could be perceived as successful, difficult, and/or a dilemma. We follow with a discussion of our findings against this background.The informants’ perceptions of successful efforts in responsible use of antibiotics, prevention of infection, improving public knowledge of antibiotic resistance, and international collaboration are in accordance with Swedish official strategies presented in our introduction, suggesting that policy rules and guidelines were being adhered to in these areas. Relevant healthcare providers also appeared to have “knowledge about antibiotic resistance, the spread of infectious diseases, compliance with basic hygiene routines and other preventive measures, knowledge about the seriousness and complexity of the issue from a global perspective,” as expected by the Swedish government .The Swedish context of this study may have contributed to informants’ perceptions of success in these areas. The use of antibiotics differs across Europe, with the lowest level of antibiotic use in Northern countries, and highest in Mediterranean countries . Many faImplementation of health strategies and policies is also influenced by context . NationaDifferences in human behavior and attitudes is one example of how adhering to policy guidelines was not always straightforward. At the end of 2018, 19.1% of the Swedish population were foreign-born . PC clinAdhering to policy guidelines regarding the use of antibiotics was also not so straightforward, and could even be a dilemma for physicians in both primary and hospital specialist healthcare levels. This is in accordance with a Swedish study on general practitioners’ perceptions of infectious disease management in primary care, which revealed the conflict that could be experienced between wanting to preserve the effectiveness of antibiotics for the future, and helping suffering patients . PC physPolicymaking informants’ observations of how younger doctors dared not question older doctors’ attitudes to antibiotic use point to another challenge yet to overcome, the issue of power in the medical hierarchy in hospitals. Students, during their medical training, learn to accept this hierarchical structure, and their place in it . New in In view of the above, and, as stated by policymaking informants, there was a need for continual behavior change regarding antibiotic prescribing in hospitals. For decades, antimicrobial stewardship programs in hospitals have focused on ensuring proper use of antimicrobials to improve patient care, reduce hospital costs, lessen the risk of adverse effects, and reduce or stabilize resistance levels . More emStress was perceived to be a hinder to antibiotic resistance work in both hospitals and primary care. How physicians perceive the stressful work environment, high patient volumes, inadequate staffing, bed shortages, or fatigue in Swedish hospitals has been documented in recent studies , 29. As Most informants, including policymaking informants, appeared to be concerned about resources, the funding of work to contain antibiotic resistance. In our study, policymaking informants seemed to be well informed about problem areas in both primary and hospital care. Their extensive knowledge of antibiotic resistance, and of international collaborative efforts was based on actual experience. In this context, they were experts in their fields. Their concerns about not enough resources and financing of antibiotic resistance efforts was interesting, and may reflect their dedication to antibiotic resistance work. On the other hand, it is possible they indicate the limitation of their position, that of being looked upon solely as experts, and implementers of policies. If this is the case, one can wonder to what extent they are able to influence changes, for example, point to areas in need of improvement.Many of the informants were not aware of the ‘One Health’ concept. This appears to be one area where governmental expectations described in the introduction have not been met. However, this has been observed among healthcare workers in other countries as well, who did not find ‘One Health’ to be relevant in their daily practice of medicine . This isBased on the discussion above, we suggest that the sense of relative success of policies to contain antibiotic resistance in Sweden so far fits well into McConnell’s description of ‘resilient success’ , in thatTo the best of our knowledge, this is the first qualitative study that describes how healthcare providers in different levels of Swedish healthcare perceive their efforts to contain antibiotic resistance. As with all qualitative studies, informants’ realities can be interpreted in various ways, and can depend on the researcher’s subjective interpretation. An important issue in qualitative content analysis therefore is achievement of trustworthiness . Four wiFor practical and financial reasons, our informants were recruited from, and interviews were conducted in four cities in middle and southern Sweden. In striving for credibility, informants from different levels of healthcare were strategically chosen, so as to increase knowledge of efforts to contain antibiotic resistance from these perspectives. In striving for dependability, the research process was described in detail to make it possible, first, for the reader to understand the logic of the findings, and secondly, to enable a future researcher to repeat the process. To assure confirmability, citations were used to show that the results were grounded in the informants’ experiences and perceptions. Our findings are based on the perceptions of a small sample size of informants from each healthcare level, and cannot be generalized. While there is a possibility the findings can be transferred to other healthcare settings in Sweden, the Swedish context can be a hinder regarding the extent to which they can be transferred to settings or groups outside the country. The overall goal was to gain knowledge of and describe the everyday practice of policy implementation. Data saturation was not our primary focus. Interviews with our strategic sample of informants, although few in number, resulted in an abundance of data, which gave valuable real-life glimpses of how national policies can be translated into daily practice. And, as we note in our discussion, the findings are very much in keeping with previous research. The research team was comprised of researchers with different healthcare backgrounds, pharmacy, medicine, and dentistry. Discussions during the process of the study and drafting of the manuscript revealed these different perspectives and assumptions, which contributed to a deeper understanding of the data, and improving the rigor and quality of the study.This study has given in-depth insight into how a group of healthcare policymakers and practitioners perceived the everyday practice of containing antibiotic resistance in Sweden. It has revealed their perceptions of successful efforts to combat antibiotic resistance so far, and their perceptions of problem areas in different healthcare levels. Areas to focus on in future policies have been brought to light, most notably more emphasis on attitude and behavior change, and increasing awareness of antibiotic resistance among both healthcare practitioners and patients. Thus far, these areas have not undermined the core achievements of Swedish national policies. Even so, efforts must continue. Antibiotic resistance will most probably remain a challenge for a long time to come, in Sweden, and the rest of the world.S1 Checklist(PDF)Click here for additional data file.S1 Data(DOCX)Click here for additional data file.