Family medicine physicians’ perception and attitudes of herbal substances use in greater Lisbon region

Accepted Manuscript

Family medicine Physicians’ perception and attitudes of herbal substances use in greater Lisbon region A Pereira da Silva , Marta Geraldes , Ana M. D´ıaz-Lanza , Ilona Kovacs , M Ceu ´ Costa PII: DOI: Reference:

S0944-7113(18)30140-5 10.1016/j.phymed.2018.04.040 PHYMED 52479

To appear in:

Phytomedicine

Received date: Revised date: Accepted date:

17 June 2017 24 March 2018 16 April 2018

Please cite this article as: A Pereira da Silva , Marta Geraldes , Ana M. D´ıaz-Lanza , Ilona Kovacs , M Ceu ´ Costa , Family medicine Physicians’ perception and attitudes of herbal substances use in greater Lisbon region, Phytomedicine (2018), doi: 10.1016/j.phymed.2018.04.040

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ACCEPTED MANUSCRIPT Family medicine Physicians’ perception and attitudes of herbal substances use in greater Lisbon region

A Pereira da Silvaa,*, Marta Geraldesb, Ana M. Díaz-Lanzac, dIlona Kovacsd, M

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Céu Costab,e,f

a

Health Care Unit Alameda, Ministry of Health, Lisbon, Portugal.

b

CBIOS - Research Center for Biosciences & Health Technologies, Lisbon,

Portugal.

Biomedical Sciences Department, Faculty of Pharmacy, University Alcala,

Alcala de Henares, Madrid, Spain. d

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c

Research Center in Economic and Organizational Sociology, Lisbon School of

Economics & Management, University of Lisbon, Portugal. e

NICiTeS – Nucleus of Research in Health Sciences and Technologies, ERISA

- Escola Superior de Saúde Ribeiro Sanches, Lisbon, Portugal. f

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R&D unit, Mass Spectrometry Laboratory, Faculty of Sciences, University of

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Lisbon, Portugal.

*

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Corresponding author:

Alda Pereira da Silva Health Care Unit Alameda,

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Rua Carvalho Araújo, 1900-138 LISBOA, Portugal Phone: +351 218 105 000 Mobile: +351 966 649 533 E-mail address: [email protected]

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ACCEPTED MANUSCRIPT ABSTRACT Background: Previous works showed patients preference for herbal substances (HS) although they also highlighted a discrepancy with physicians’ adherence to HS and its recommendation. Hypothesis/Purpose: This study aimed to assess physician’s perception and attitudes concerning the use of HS for their patients in a Family Medicine

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approach.

Study Design: Observational cross-sectional exploratory study.

Methods: A questionnaire survey was applied to National Health System

physicians; 113 questionnaires were distributed in the Greater Lisbon region.

Results: 80 valid questionnaires were received. The age of participants ranges

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from 29 to 64 with mean age of M ± SD:51.9 ± 10.0y, mostly women (71.4%). Of these, 61.5% were unaware of traditional herbal medicinal products’ (THMP) legal recognition and 67.3% of the difference between THMP and wellestablished use medicines. Absence of accordance between use and knowledge of herbal medicines (HM) / herbal products (HP) (p = 0.025) can be

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related to lack of Phytotherapy knowledge perception based on the nonexistence of specific training reported by 94.0% of physicians.

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Through factor analysis, three dimensions were obtained: Factor1, "Use"; Factor2, "Autonomy"; Factor3 "Effort". The overall Cronbach's α was 0.77, and

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0.82 for Factor1. The evidence of use/prescription, has a correlation with "Use" (p < 0.0001), willingness to prescribe (p < 0.0001) and self-medication (p <

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0.0001). There is a correlation (r = 0.605, p < 0.0001) between HS recommendation and self-medication. There were differences in use, perception

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and attitudes among Personalized-Health-Care Units and Family-Health Units physicians in relation to Factor1: p = 0.007 and Factor2: p = 0.021, age (p = 0.001), years of Medical career (p = 0.002), HM use (p = 0.014) and information about alternatives (p = 0.03). Physicians who answered correctly to the question on silymarin had higher scores in factor1 than those who did not: 1.76 vs 1.25 (p = 0.019). Conclusion: Low adherence to HS and little use of HM/HP were confirmed, highlighting the need for specific knowledge in Phytotherapy and its regulatory framework. This knowledge will enable the evaluation of herb-drug interactions 2

ACCEPTED MANUSCRIPT and HM/HP adverse effects by the physicians thus justifying the integration of programmatic contents about HS in Medical Education. Keywords: Family medicine; Phytomedicine; Phytotherapy; Traditional herbal medicines; Medical education.

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Abbreviations

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AIDS: Acquired Immunodeficiency Syndrome, CAM: Complementary and Alternative Medicine, EAS: European Advisory Services, EC: European Commission, EMA: European Medicines Agency, ESCOP: European Scientific Cooperative on Phytotherapy, EU: European Union, THMP: Traditional Herbal Medicinal Products, FHU: Family Health Units, GMP: Good Manufacturing Practices, HM: Herbal Medicines, HP: Herbal Products, HS: Herbal Substances, MA: Market Authorization, OTC: Over-the-counter, PHCU: Personalized Health Care Units, SD: Standard deviation, SmPC: Summary of Product Characteristics, SPSS: Statistical Package for Social Sciences, WHO: World Health Organization

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ACCEPTED MANUSCRIPT Introduction Phytotherapy was used for the first time by physician Henri Leclerc to relate “phyto”/herbal substances with therapy through herbal products (HP) in clinical practice (Eugène-Humbert Guitard, 1955). Plant therapy or phytotherapy currently involves herbal medicines (HM) and traditional herbal medicinal products (THMP) (European Parliament and Council, 2004). Medicinal plants as

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a whole or in parts are constituents of herbal medicines, but they are also included in the composition of food and floral supplements, homeopathic

medicines and products that are called nutraceuticals and functional foods outside Europe. Many of these products, over-the-counter (OTC), non-

prescription, are increasingly available to patients for self-medication and can

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be used inappropriately. This possibility is exacerbated by the fact that, in

general, only 33% of users inform the physician they are consuming HP (Mehta, Gardiner, Phillips, & McCarthy, 2008).

Numerous plants are part of the constitution of food supplements for which

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therapeutic claims are not allowed. This segment of products represents about 15-20% of the European market for HP, depending on the country (Bilia, 2015).

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They may present health claims, based on physiologically based actions scientifically accepted in Europe (European Advisory Services (EAS), 2007). Directive 2002/46/EC, Regulation 2009/1170 and Regulation 432/2012 /EC

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establish the current legislation for food supplements from the perspective of

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consumers and health professionals. It is very relevant to know the benefit / risk relation of the use of medicinal plants since the quality of the food supplements is not under GMP (Good

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Manufacturing Practices) or equivalent requirements, and they are notified but not evaluated in most European countries. It is crucial that health professionals are aware of the different HP options available on the market and have adequate knowledge of medicinal plants and their use. The plants are also active constituent sources used in the manufacture of medicines or as origin for new chemical entities design. According to World Health Organization (WHO), use of isolated chemical constituents, however, even when pure, does not constitute what is denominated as Phytotherapy. 4

ACCEPTED MANUSCRIPT Previous works showed that patients prefer HP as a soft approach for positive treatment outcome under certain clinical conditions and simultaneously reveal that medical students’s and physician’s acceptation of this approach is not always in line with its clinical practice associated with formative deficiency (Ameade, Amalba, Helegbe, & Mohammed, 2015; Clement et al., 2005; Pereira da Silva, Geraldes, Díaz-Lanza, Kovacs, & Costa, 2017).

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Since 2004 the European Directive 2004/24/EC, transposed later as DecreeLaw 176/2006 in Portugal and Royal Decree-Law 1345/2007 in Spain, is

providing a simplified registration procedure for THMP, which allows therapeutic indications and ensures quality, including purity and reproducibility of

constituents (only plants), guarantying safety to patients and physicians. The

transposition of the 2001/83/EC.

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same legislation applies to HM which were previously introduced with the

Despite these legislative aspects, many physicians have a critical view on the therapeutic use of medicinal plants (Furst & Zundorf, 2015) although there are substantial pharmacological studies of their constituents and several

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randomized double-blind clinical trials, similar to the new chemical entities. Even more, there is a gap between physicians acceptance and knowledge of

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HS / HM so that educational intervention would promote better communication with patients on this modality (Abuduli & Aljunid, 2015; Clement et al., 2005).

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In this context, it is pertinent to evaluate perception and attitudes of Family Medicine Portuguese physicians concerning the use of HS since Phytotherapy

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has been regulated in Portugal as a non-conventional therapy within the National Health System. It is fixed the characterization and functional content of

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the profession of Phytotherapist (Portaria-207-E, 2014) and regulated the general requirements that must be satisfied by the cycle of studies leading to a degree in Phytotherapy(Portaria-172-B, 2015). This study aimed to characterize, in Family Medicine, the clinical practice with herbal substances focusing on: -

Prescribing habits of Phytotherapy and its determinants: adherence and knowledge.

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Perceived existence of knowledge about HS/HP/HM underlying this eventual practice/use and how this knowledge, if existing, was acquired.

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Perception and attitudes regarding the prescription / recommendation of herbal medicines / herbal food supplements.

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Material and methods

An exploratory, cross-sectional study was performed in a sample of physicians exerting functions in Health Centers / Family Health Units in the Greater Lisbon region. The study used as a tool to collect information a questionnaire survey

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(see Appendix 1), adapted from a previously tested questionnaire (Clement et al., 2005) to the Portuguese context, to anonymously characterize the clinical practice of using HS/HP/HM.

The questionnaire consisted of 25 questions including: 1. Prescribing habits and their determinants: adherence to Phytotherapy, knowledge, prescription mode

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(circumstances, type and reasons); 2. Perception of the existence of knowledge and how it was acquired; 3. Perception / attitudes regarding the prescription /

scale was used.

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recommendation and 4. Interest / training needs for doctors. A 5-value Likert

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One hundred and thirteen questionnaires in paper were distributed personally in 38 Health Centers in the Greater Lisbon region, with 28 Centers answering

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(87.5%), amounting to 80 valid questionnaires, which corresponds to physicians who showed willingness to collaborate in the study (71%). The study was launched at the end of 2011 with the elaboration and validation of the

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questionnaires, whose application and treatment were extended until 2014. Statistical analysis was performed using the SPSS (Statistical Package for Social Sciences), version 21. Statistical methods used were the Student-t test to compare the average levels of extracted factors (after factor analysis for the extraction of the main components) in regard to parametric variables or their non-parametric equivalent; ANOVA or its non-parametric equivalent, in regard to more than two variables. To investigate the association between categorical variables we used Chi-square test. To evaluate the correlation between 6

ACCEPTED MANUSCRIPT variables, we used the Pearson correlation coefficient (r) and, Spearman (rho) when variance homogeneity was not observed. For the purpose of statistical inference, a significance level of α = 5% was established, representing a pvalue less than alpha, a statistically significant result.

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Ethics and data protection The confidentiality of all individuals in the sample was guaranteed.

The present study had the approval of the Ethics Committee of the Lusófona University of Humanities and Technologies and was followed by the public

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institution of Central Administration of the Health System.

Results

The sample is constituted mainly by women (71.4%) ages from 29 to 64 (mean age ± SD: 51.9 ± 10.0). Most physicians belong to the age group 50-59

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(58.2%) and 52.6% had over 30 years in the Medical career. Among respondents, 55% have medical expertise (Specialist degree, of which

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36.3% from Family Medicine) and 12.5% had completed a Master's degree. It was found that 49.4% are Graduate Assistants and 16.5% are at the top of the

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Medical career (Graduate Assistant Seniors). The majority (75.7%) do not practice private medicine. As for the employment connection, 55.1% reported

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working in Family Health Units (FHU) and 44.9% in Personalized Health Care Units (PHCU). Physicians practicing Family Medicine in the FHU belong to

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younger age groups compared to doctors in PHCU (p = 0.001), and 32.6% are under the age of 40 (at FHU) while only 2.9% in PHCU. The opposite is true for ages over 60: 4.7% in the FHU compared to 23.5% in PHCU. Most practice medicine in urban areas. It was found that there is little familiarity with legislative aspects: 61.5% of respondents are unaware of the legal recognition of THMP and 67.3% are unaware of the difference between well-established use HM and THMP.

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ACCEPTED MANUSCRIPT Except for valerian (Fig. 1) and Ginkgo biloba, most physicians cannot identify the names of plants in the Portuguese pharmacies market, however, they perceive themselves as knowledgeable and prescribe/recommend HM/HP. Moreover, they cannot identify medicinal plants present in the HM/HP which they claim to know and prescribe/recommend. Thus, differences were found between the perception of knowledge and the attitude to prescribe versus real knowledge of the related HS or herbal preparation (p = 0.025) as for Legalon®

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(Fig. 1).

Additionally, respondents have the perception that there is a lack of

Phytotherapy knowledge, which was confirmed and is objectively justified by the absence of training reported in 94% of the physicians surveyed.

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Our findings reveal that 43% of the surveyed individuals state they seldom or never ask patients if they use herbal products (Fig. 2). Similarly, most do not

inform the patient of other therapeutic approaches and 64.7% state unfamiliarity with alternatives (Fig. 2).

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It was found there is a perception that colleagues which are professional role model references, as well as patients, would not appreciate an approach based

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on HM (Fig. 3).

There is still a perception of autonomy, as well as openness / predisposition to

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the use / prescription of HM (Fig. 4 and Fig. 5). Prescribing HM, however, would require the interviewed physicians some effort

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in achieving specific knowledge, for which they recognize the importance of specialized training (Fig. 6).

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Through factor analysis three dimensions or major components were obtained under the "Perception and Attitudes": Factor 1, "Using" Factor 2, "Autonomy" and Factor 3 "Effort". The overall Cronbach's α was 0.77, and 0.82 for Factor 1. The results show that objectification of the HS/HM medical prescription has a strong correlation with the perception of adherence and attitudes of physicians when interviewed about the prescription of HS/HM (p < 0.0001) and a will to prescribe HS/HM (p < 0.0001) as well as for HS/HM physician self-medication (p < 0.0001), showing consistency in responses and attitudes, and there is still 8

ACCEPTED MANUSCRIPT a positive correlation (r = 0.605, p < 0.0001) between the indication of HS/HM/HP on the patient and for their own use (Table 1). There were differences in physicians’ use habits, perception and attitude toward herbal products between those who work in FHU and in PHCU, particularly concerning Factor 1: p = 0.007 and Factor 2: p = 0.021; age (p = 0.001), years in Medical career (p = 0.002), use of herbal drugs (p = 0.014) and regarding

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information about alternatives (p = 0.03) (Table 2). Results indicate a gender difference in perceiving the effort required to obtain knowledge related to HM/HP (p = 0.026), with women perceiving the greatest effort (Table 2).

There were significant differences in the use of HM/HP in

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prescription/recommendation according to academic degree (p = 0.016), and differences between undergraduate and master's degrees (p = 0.003) also between specialists and master's degrees (p < 0.0001) (Table 2). Finally, comparing calculated scores of Factor 1 concerning the practice of

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using HM/HP, including prescribing HS as an alternative therapy, in complementary use or even attending to a patient request, to verify its

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coherence there is a significant relation with the prescription history. The score in the category "prescription as an alternative" is 1.73 compared to 0.69 in the

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category "does not prescribe" thus distinguishing individuals who prescribe as an alternative to those who do not prescribe at all (p = 0.001).

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On the other hand, regarding knowledge, doctors who provided a correct answer (True /False) on the silymarin question (“Silymarin is a group of natural

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compounds - silybin, silidianin and silicristin - with hepatoprotective properties”) had higher scores in Factor 1 Perception and Attitude - "Use" than those who did not (Score 1.76 vs. 1.25; p = 0.019). This is also consistent with the correlation between not informing the patient about alternatives due to lack of knowledge (Fig. 5). An association between Factor 1 and the type of recommendation on HM/HP (p = 0.016) was verified and there is also consistency between the negative perception and action (F1) and the non-recommendation of HM/HP (p = 0.006), 9

ACCEPTED MANUSCRIPT being verified as opposed to a positive correlation between perception and attitude/use of HM/HP (F1) with either prescription (P3) (r = 0.481, p < 0.001) or self-consumption (P8) (r = 0.418, p = 0.001) (Table 1). There was a strong correlation (rho = 0.599, p < 0.0001) between knowledge and willingness to use / prescribe HM/HP. Additionally, the perception and positive attitude towards using / prescribing, were positively correlated with the

very important (r = 0.518, p < 0.0001) (Table 1).

Discussion

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willingness to get training (r = 0.618, p < 0.0001), being training considered as

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The lack of knowledge on legislation among medical health professionals, in

particular the existence of legal recognition of THMP, may partly explain the low adherence to the prescription/recommendation of HM/HP (Pereira da Silva et al., 2017).

The lack of information about medicinal plants, which is recognized by the

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interviewed physicians, can also justify the poor adherence to the overall approach and low use of HM/HP. It is important to note that HP are being used

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by patients either by self-medication or under the guidance of alternative therapists, and the awareness of the physician about this use is not always

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observed (Fig. 2).

Physicians should, however, be aware of the physiological and therapeutic

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effects of medicinal plants as well as potential interactions with conventional medicinal products from a view point of pharmacovigilance and safe use by the

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patient (Krenn et al., 2013). Physicians are expected not only to counsel and recommend HS based on their knowledge and evidence, but also to increase patient confidence and compliance with the available therapeutic options by preventing the occurrence of possible interactions between HS and medicinal drugs (Izzo, Hoon-Kim, Radhakrishnan, & Williamson, 2016). The insufficient specific knowledge on herbal products was verified to be the origin for not informing or advising about them, leading to a lack of communication as observed in the study sample (Fig. 2). It may also lead to the lack of effective 10

ACCEPTED MANUSCRIPT communication between different health care providers, which contributes to an added risk of the patient consuming non-controlled products without the physicians’ awareness, which may threaten patient safety (Stub et al., 2016). When the physician neglects to question whether there is use of HS, and the patient does not report it, adopting a “don’t ask, don’t tell ” attitude (Giveon, Liberman, Klang, & Kahan, 2003), the use of these products is often relegated,

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with no supervision by health professionals. In fact, although there is a perception that HM are safe when used

concomitantly with other prescription medications, this is not always the case, whereby optimization of medical care, in which physicians are aware of the potential risks and therapeutic benefits of indicating medicinal plants, is an

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attainable goal in the name of good clinical practice.

The special case of poly-medicated patients, such as AIDS patients, shows that unawareness of health professionals on the use of HS by their patients (48 in 94, according to Nlooto) may be relevant in perceiving and understanding

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potential adverse effects that may arise with the concomitant use of therapies (Nlooto, 2015). The same applies to the use of herbal food supplements that

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may lead to adverse effects (Cellini et al., 2013). An enquiry to know all the products that a patient use, whether OTC, vitamins,

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minerals, dietary supplements, herbal medicines and, simply, herbal teas, are essential parameters to consider in a medical consultation and hospital

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admission of new patients. Holmes et al. (Holmes, Kaiser, Jackson, & McPherson, 2010) reported the risk of admission to palliative care clinics, where the drug profile was insufficiently recorded, putting patients at high risk for

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interactions and safety issues (Fasinu, Bouic, & Rosenkranz, 2012). On the other hand, physicians’ need to advice patients and for this purpose need to know alternative therapies when patients inquire about them, which is not always observed (Fig. 2). Coherence revealed by physicians questioned between adherence, selfmedication and prescription is relevant, as well as awareness about the importance of medical training in this area of knowledge (Table 1).

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ACCEPTED MANUSCRIPT Even if physicians understand that their reference peers would not appreciate it if they prescribed herbal medicines, this would not make them act according to their peers’ thought, which reveals autonomy in prescription (Fig. 3 and 4). Moreover, interviewed physicians would prescribe phytomedicines if they knew that it was their patients’ will (Fig. 2). This fact revealed empathy towards the patient and accessibility as well as openness to different therapeutic approaches but the scarce information may underlie doctor-patient

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communication concerns.

A better knowledge of medicinal plants was linked to a greater adherence and use of Phytotherapy, with more information provided to the patient, which proves the importance of training in this area (Table 2).

Having autonomy and openness to prescription but lack of training would

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require an additional effort from physicians, in particular for women, which can be explained by multiple family responsibilities (Table 2, Fig.s 4, 5 and 6). Herbal food supplements are products for which therapeutic claims are still not permitted but are being considered, in a fitness roadmap (European

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Commission, 2015), to be regulated by food European laws, are not part of the pharmaceutical legislation, thus out of the pharmacovigilance system. The

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pharmaceutical quality of many HP used in complementary medicine might be cause for concern, since most of these products are not licensed as medicines,

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and therefore the evidence of quality, efficacy and safety is not required before marketing (Cañigueral et al., 2008). A registration dossier is nowadays throughout the EU a requirement for the commercialization of any HP intended

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to be used as medicinal product, for which preclinical and clinical studies are available to ensure well-established use, as well as the efficacy based on

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knowledge in literature and evidence accumulated through several generations for the traditional use based on the products’ MA (Cañigueral et al., 2008). Additionally, integrating complementary and alternative medicine teaching in the education of health professionals, with accurate strategies to organize and instruct knowledge (Lee et al., 2007) is a necessary measure to allow overcoming communication difficulties and improving appropriate HS advice. The lack of Phytotherapy knowledge has also been verified among other health professionals such as community pharmacists (Volmer, Lilja, Hamilton, Bell, & 12

ACCEPTED MANUSCRIPT Veski, 2011). Nevertheless, most pharmacies in the EU as well as worldwide have a Phytotherapy section. Most likely based on the scarce registration of HP as well as limited discussion concerning HS and HP value, there are other reports on limited knowledge and teaching about medicinal plants in the formal education of health professionals (Abuduli & Aljunid, 2015; Canna & Rajesh, 2012; Xu & Levine, 2008) which is in line with our results (Fig. 1).

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This aspect was recognized by medical students, who have identified the importance of obtaining this knowledge (Ameade et al., 2015). Medical students indicated that they do not have the expertise to advise, prescribe or prevent

patients from taking medicinal plants, despite the interest and social demanding due to curiosity and acceptability of these therapies in the contemporary society

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(Karpa, 2012). Thus, it seems imperative that health professionals work

together in order to have a coherent approach that is built for the protection of patients. An integrated model of health care delivery would promote standards for best practices, leading to potential benefits in the clinical approach (Molassiotis et al., 2005).

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In addition, there are several myths about the use of HM, with health professionals holding different opinions on the recognition of their efficacy and

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acceptability, despite the understanding that traditional use, namely herbal tea formulations, has for centuries improved physiological functions, prevented

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diseases and promoted symptomatic relief of several disorders, as well as being perceived by users as a less aggressive treatment for mild disorders (Canna &

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Rajesh, 2012; Fakeye & Onyemadu, 2008). In this context, there are two main bottlenecks: one is the sceptic view that scientific methods, which are common

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in therapeutic practice, are not applied when registering THMP (Jütte et al., 2017) but from our point of view, the criteria of evidence-based medicine is only met by EMA (European Medicines Agency) after all available facts are assessed and evaluated in a public assessment report, which addresses systematic reviews and meta-analyses over and above the formally stipulated regulatory provisions (30 years, product reference). The other bottleneck is the lack of awareness from the general public on the safety limitations of HP, eventually because at least in some countries in the EU, few HP are marketed as licensed medicines and have SmPC (Summary of Product Characteristics) 13

ACCEPTED MANUSCRIPT recognized as authoritative, in opposition to a large number of food supplements (EU) and herbal dietary supplements (USA) circulating either in supermarkets and drugstores or in pharmacies, despite containing the same medicinal plants. Thus, although many physicians are unaware there is an option to use HPs on their patients, those that are aware of herb-drug interactions and HP adverse

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effects generally avoid considering them as a therapeutic approach and tend to oppose the rational Phytotherapy as impelled by European Scientific

Cooperative on Phytotherapy (ESCOP) and regulated by EMA. In any case, for pharmacovigilance purposes (Navarro et al., 2017), particularly for the elderly (Sultan et al., 2015) and in specific conditions, such as during pregnancy and

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for the pediatric population, it is important that these aspects of complementary knowledge are taught and disseminated within a medical context. For instance, at least 40% of medical schools in Europe include in their programs complementary and alternative medicine (CAM) courses (Varga, Márton, & Molnár, 2006). In the case of the United Kingdom, most Medical schools have

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familiarization courses on CAM (Owen & Lewith, 2004) and in Switzerland CAM are also very popular (Nicolao, Täuber, Marian, & Heusser, 2010). A review on

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the regulatory status of CAM for medical doctors in Europe revealed that in Germany, 15,000 doctors have been trained in naturopathic medicine, which is

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used in rehabilitation clinics, in acute care hospitals and even in regular hospitals (CAMDOC Alliance, 2010). Accordingly, 70 percent of the German General Practitioners prefer to prescribe herbal medicines, which is expected,

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considering that there is specialized education on universities, as it is

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mandatory since 2003 (Jobst & Niebling, 2005). The CAM contents taught in universities worldwide are highly variable and depend on the institutions they are taught in, despite efforts already made to encourage a more accurate education system for teaching these subjects, in order to respond to the increasing demand for HP and alternative therapies by patients (Templeman, Robinson, & McKenna, 2015a, 2015b). In most European countries, like in Portugal, however, the teaching of Phytotherapy is not yet included in the curricula for Medical courses.

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ACCEPTED MANUSCRIPT The sample for this study was limited to a group of Family Medicine practitioners in a region of the country. Further studies may include other Medical Specialties and cover other regions of the country.

Conclusions

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In conclusion, the research revealed low acceptance and adherence to phytomedicine by Family Medicine Physicians, which leads either to scarce knowledge on quality, safety and efficacy issues. It also highlights that

physicians not aiming to answer and satisfy the patients’ preference for HS,

ignore as well the potential misuse of herbal substances as active ingredients of

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HM over-the-counter, or as other substances in HP available as food

supplements, or even as a daily infusion for welfare. This attitude may have underlying a lack of knowledge on legislative aspects (61.5%/67.3% unawareness) as well as an absence of appropriate information about medicinal plants, in accordance to the perception that there is a lack of information and

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training in this matter. Predominately, the type of medical doctor who does not adhere to Phytotherapy also lacks the skill to promote benefit-risk-analysis of

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OTC products taken by patients in therapeutic practice. The lack of teaching/ learning in Phytotherapy in Medical Schools may

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underlying the pictured scenario on the use of herbal products, leading to an incomplete clinical interaction with patients concerning the use of HM/HP in the

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Greater Lisbon region.

Future longitudinal studies may follow the evolution of strategic alignments of

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perception and attitudes among clinicians, toxicologists and regulators, for best practices on herbal substances and herbal medicines use.

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ACCEPTED MANUSCRIPT Acknowledgments: To Prof. Doctor M Bicho for support throughout the professional and scientific path. To Prof. Doctor Luís Monteiro Rodrigues for their support and encouragement. To Cesar Oliveira for logistical collaboration. To Prof. Doctor Francisco A Ramos Leitão and to Prof. Doctor Osvaldo.

questionnaire.

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Rodrigues dos Santos for guidance in elaborating and validating the

To Jael Bernardes (MSc.) for the help in constructing the database. To Dr. Sofia Amador for bibliographic support.

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Conflict of interest

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The authors declare they have no conflict of interests.

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ACCEPTED MANUSCRIPT References

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Abuduli, M., & Aljunid, S. M. (2015). the Gap Between Knowledge and Perception on Education in Traditional and Complementary Medicine Among Medical Staff in. Malaysian Journal of Public Health Medicine, 15(1), 77–82. Ameade, E. P. K., Amalba, A., Helegbe, G. K., & Mohammed, B. S. (2015). Herbal medicine : a survey on the knowledge and attitude of medical students in Tamale , Ghana, 3(1), 1–8. Bilia, A. R. (2015). Herbal medicinal products versus botanical-food supplements in the European market: state of art and perspectives. Natural Product Communications, 10(1), 125–131. CAMDOC Alliance. (2010). The regulatory status of Complementary and Alternative Medicine for medical doctors in Europe. Cañigueral, S., Tschopp, R., Ambrosetti, L., Vignutelli, A., Scaglione, F., & Petrini, O. (2008). The Development of Herbal Medicinal Products. Pharmaceutical Medicine, 22(2), 107–118. https://doi.org/10.1007/BF03256690 Canna, J. G., & Rajesh, K. J. (2012). Influence of knowledge on attitude and practice of health care professionals regarding use of herbal medicines in a tertiary care teaching hospital : a cross-sectional survey. URPBS, 3(3), 1215–1219. Cellini, M., Attipoe, S., Seales, P., Gray, R., Ward, A., Stephens, M., & Deuster, P. A. (2013). Dietary supplements: Physician knowledge and adverse event reporting. Medicine and Science in Sports and Exercise, 45(1), 23–28. https://doi.org/10.1249/MSS.0b013e318269904f Clement, Y. N., Williams, A. F., Khan, K., Bernard, T., Bhola, S., Fortuné, M., … Seaforth, C. E. (2005). A gap between acceptance and knowledge of herbal remedies by physicians: the need for educational intervention. BMC Complementary and Alternative Medicine, 5, 20. https://doi.org/10.1186/1472-6882-5-20 Eugène-Humbert Guitard. (1955). Nos deuils : Le Dr Henri Leclerc [archive]. Revue D’histoire de La Pharmacie, 145, 74–75. European Advisory Services (EAS). (2007). The Use of Substances With Nutritional or Physiological Effect Other Than Vitamins and Minerals in Food Supplements. European Commission. (2015). Evaluation of Regulation (EC) No 1924/2006 with regard to nutrient profiles and health claims (Evaluation and fitness check roadmap), 1–8. European Parliament and Council. (2004). Directive 2004/24/EC of the European Parliament and of the Council. Official Journal of the European Union, (L 136), 85–90. Fakeye, T. O., & Onyemadu, O. (2008). Evaluation of knowledge base of hospital pharmacists and physicians on herbal medicines in Southwestern Nigeria. Pharmacy Practice (Internet), 6(2), 88–92. https://doi.org/10.4321/S1886-36552008000200005 Fasinu, P. S., Bouic, P. J., & Rosenkranz, B. (2012). An overview of the evidence and mechanisms of herb-drug interactions. Frontiers in Pharmacology, 3 APR(April), 1–19. https://doi.org/10.3389/fphar.2012.00069 17

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Furst, R., & Zundorf, I. (2015). Evidence-Based Phytotherapy in Europe: Where Do We Stand? Planta Medica, 962–967. https://doi.org/10.1055/s-00351545948 Giveon, S. ., Liberman, N., Klang, S., & Kahan, E. (2003). A survey of primary care physicians’ perceptions of their patients’ use of complementary medicine. Complementary Therapies in Medicine, 11(4), 254–260. https://doi.org/10.1016/S0965-2299(03)00114-6 Holmes, H. M., Kaiser, K., Jackson, S., & McPherson, M. L. (2010). Soliciting an herbal medicine and supplement use history at hospice admission. Journal of Palliative Medicine, 13(6), 685–694. https://doi.org/10.1089/jpm.2009.0378 Izzo, A. A., Hoon-Kim, S., Radhakrishnan, R., & Williamson, E. M. (2016). A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and Drug Interactions of Herbal Remedies. Phytotherapy Research : PTR, 30(5), 691–700. https://doi.org/10.1002/ptr.5591 Jobst, D., & Niebling, W. (2005). Naturheilverfahren als Teil der akademischen Lehre und die Rolle der Allgemeinmedizin. Forschende Komplementärmedizin / Research in Complementary Medicine, 12(5), 272– 276. https://doi.org/10.1159/000088316 Jütte, R., Heinrich, M., Helmstädter, A., Langhorst, J., Meng, G., Niebling, W., … Trampisch, H. J. (2017). Herbal medicinal products – Evidence and tradition from a historical perspective. Journal of Ethnopharmacology, 207(March), 220–225. https://doi.org/10.1016/j.jep.2017.06.047 Karpa, K. (2012). Development and implementation of an herbal and natural product elective in undergraduate medical education. BMC Complementary and Alternative Medicine, 12(57), 1–10. https://doi.org/10.1186/1472-688212-57 Krenn, L., Bilia, A. R., Costa, M. C., Hook, I., Steinhoff, B., & Wegener, T. (2013). Now Ginkgo - 10 years after Cimicifuga? Phytomedicine, 21(1), 98– 99. https://doi.org/10.1016/j.phymed.2013.10.001 Lee, M. Y., Benn, R., Wimsatt, L., Cornman, J., Hedgecock, J., Gerik, S., … Haramati, A. (2007). Integrating complementary and alternative medicine instruction into health professions education: organizational and instructional strategies. Academic Medicine : Journal of the Association of American Medical Colleges, 82(10), 939–945. https://doi.org/10.1097/ACM.0b013e318149ebf8 Mehta, D. H., Gardiner, P. M., Phillips, R. S., & McCarthy, E. P. (2008). Herbal and dietary supplement disclosure to health care providers by individuals with chronic conditions. Journal of Alternative and Complementary Medicine (New York, N.Y.), 14(10), 1263–1269. https://doi.org/10.1089/acm.2008.0290 Molassiotis, A., Fernadez-Ortega, P., Pud, D., Ozden, G., Scott, J., Panteli, V., … Patiraki, E. (2005). Use of complementary and alternative medicine in cancer patients: a European survey. Annals of Oncology, 16(February), 655–663. https://doi.org/10.1093/annonc/mdi110 Navarro, V., Khan, I., Björnsson, E., Seeff, L. B., Serrano, J., & Hoofnagle, J. H. (2017). Liver Injury from Herbal and Dietary Supplements HHS Public Access. Hepatology, 65(1), 363–373. https://doi.org/10.1002/hep.28813 Nicolao, M., Täuber, M., Marian, F., & Heusser, P. (2010). Complementary medicine courses in Swiss medical schools: actual status and students’ 18

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experiences. Swiss Medical Weekly, 140(May), 44–51. Retrieved from http://www.smw.ch/docs/PdfContent/smw12760.pdf%5Cnhttp://smw.ch/docs/PdfContent/smw-12760.pdf Nlooto, M. (2015). Views and experiences of healthcare professionals towards the use of African traditional, complementary and alternative medicines among patients with HIV infection: the case of eThekwini health district, South Africa. BMC Complementary and Alternative Medicine, 15(1), 170. https://doi.org/10.1186/s12906-015-0687-3 Owen, D., & Lewith, G. T. (2004). Teaching integrated care: CAM familiarisation courses. Medical Journal of Australia, 181(5), 276–278. https://doi.org/owe10062_fm [pii] Pereira da Silva, A., Geraldes, M., Díaz-Lanza, A., Kovacs, I., & Costa, M. C. (2017). Adherence of family medicine physicians to therapy based on medicinal plants in a Greater Lisbon sample: a first survey. Biomedical and Biopharmaceutical Research Journal, 1(14), 60–74. https://doi.org/10.19277/BBR.14.1.150 Portaria-172-B. Ministérios da Saúde e da Educação e Ciência, 1.a série Diário da República, 5 de junho de 2015 3636–(10)–3636–(12) (2015). Portaria-207-E. Ministérios da Saúde e do Ensino Superior (2014). Stub, T., Quandt, S. A., Arcury, T. A., Sandberg, J. C., Kristoffersen, A. E., Musial, F., & Salamonsen, A. (2016). Perception of risk and communication among conventional and complementary health care providers involving cancer patients’ use of complementary therapies: a literature review. BMC Complementary and Alternative Medicine, 16(1), 353. https://doi.org/10.1186/s12906-016-1326-3 Sultan, S., Rabaiya, M. V., Jamil, A. A., Jahangir, T. A., Viqar, M., Ali, R., … Jahangir, A. (2015). Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease. J Patient Cent Res Rev, 2(4), 174–191. https://doi.org/10.17294/2330-0698.1212 Templeman, K., Robinson, A., & McKenna, L. (2015a). Integrating complementary medicine literacy education into Australian medical curricula: Student-identified techniques and strategies for implementation. Complement Ther Clin Pract, 21(4), 238–246. https://doi.org/10.1016/j.ctcp.2015.09.001 Templeman, K., Robinson, A., & McKenna, L. (2015b). Student identification of the need for complementary medicine education in Australian medical curricula: A constructivist grounded theory approach. Complementary Therapies in Medicine, 23(2), 257–264. https://doi.org/10.1016/j.ctim.2015.02.002 Varga, O., Márton, S., & Molnár, P. (2006). Status of Complementary and Alternative Medicine in European Medical Schools. Forschende Komplementarmedizin, 13(1), 41–45. https://doi.org/10.1159/000090216 Volmer, D., Lilja, J., Hamilton, D., Bell, J. S., & Veski, P. (2011). Self-reported competence of Estonian community pharmacists in relation to herbal products: Findings from a health-system in transition. Phytotherapy Research, 25(3), 381–386. https://doi.org/10.1002/ptr.3266 Xu, S., & Levine, M. (2008). Medical residents’ and students’ attitudes towards herbal medicines: a pilot study, 15(1), 9–12.

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ACCEPTED MANUSCRIPT Appendix 1: Topics of the questionnaire, not including the boxes of the five-points Likert scale of the applicable version, by the extension of the text.

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1.1 - Have you heard about the legal recognition of traditional herbal medicinal products (Directive CE / 24/2004)? 1.2 - Know the difference between herbal medicine and traditional herbal medicine? 2 - To what extent do you consider that there is a potential benefit in using different categories of herbal products? a) Medicinal herbs b) Herbal dietary supplements c) herbal medicinal products d) traditional herbal medicinal products. 3 - Have you ever recommended / prescribed and 8 - Have you ever used on yourself, different categories of herbal products? a) Medicinal herbs b) Herbal dietary supplements c) herbal medicinal products d) traditional herbal medicinal products. 4 - From the following plants, indicate the ones that you have ever recommended / prescribed (list of medicinal plants presents in the Portuguese market) Hypericum perforatum Ruscus aculeatus Cardus marianus Harpagophytum procumbens Centella asiatica Vaccinium myrtillus Panax ginseng Ginkgo biloba Serenoa repens Echinacea purpurea Valeriana officinalis Erisimo officinalis Plantago ovata Ananas aivense Cassia angustifolia Cynara scolymus Vitex agnus castus. Others? Which ones?..........................

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5 and 6 - Do you prescribe herbal medicines (5) / recommend herbal teas or supplements (6) as a therapeutic alternative, in addition to or at the request of the patient or I do not recommend? (Tick one or more boxes) 7 - Have you ever recommended to your patients the use of non-conventional therapy (designation according to Law 45/2003) using herbal products? a) If so, which system? 8 – If self-consumption of herbal products, 9 - if yes, you have done so through (please tick one or more options) a) Prescription / recommendation from another physician b) Recommendation of pharmacist c) Recommendation of therapist of unconventional therapies d) Self-medication e) Other route. Which one? 10 - The recommendation of herbal supplements to patients is particularly indicated? 11 - Do you ask patients if they use herbal products? 12.1 - In the event of possible alternative therapy with herbal medicines, do you inform the patient? 12.2 - If you do not inform, what is the reason? (tick one or more boxes) a) Disagree the type of therapy b)Unknown alternatives c) Not having confidence in the type of medicines d) Consider that the doctor is the one who knows e) Consider that plant treatment is with naturopath f) Not to foster dialogue on a complex issue g) Other reason. Which one? 13 - Do you consider it is important to include therapy with herbal medicinal products in medical training? 14.1 - Have you ever had training in the area of plant therapy? What kind? a) Phytotherapy b) Homeopathy c) Naturopathy d)Ayurveda e)Traditional Chinese Medicine f) Other. Which one? 14.2 - If yes, where? 15 - Would you like to deepen your knowledge of clinical practice with herbal medicines? 16 - Of the following medicines / food supplements, please indicate the ones you know (one side) and prescribe (other side), please tick the boxes (list of 23 trade marks for herbal products available for sale in pharmacies in Portugal): Livetan, Madecassol, Valdispert, Agiolax, Cyclo 3, Premkor, Difrarel, Euphon, Prontolax, Ginsana, Ginkoftal, Biloban, Legalon, Alacre, Acutil, Permixon, Vitacê, Gincoben, Harpadol, Xonkor, Ananase, Promil, Cholagutt. 17 From the following five affirmations mark the one (s) you think is correct: a. Homeopathy as Phytotherapy, use only plants; b. Chamomile (Matricaria chamomilla), as well as Garlic and Ginkgo biloba, potentiate the anticoagulant effects of Varfine® (warfarin); c. Silymarin is a group of natural compounds (silybin, silidianin and silicristin) with hepatoprotective properties; d. Licorice is a cause of secondary hypertension; e. There is evidence to support the efficacy of herbal products in hyperlipidemia, with a reduction in total and LDL-C, mostly without significant adverse effects 18 - My patients would appreciate if I prescribe herbal medicines (HM) 19 - I think colleagues who are a professional reference to me would appreciate if I prescribed HM 20 - If I wanted to, I could prescribe herbal medicines because I feel with knowledge to do so. 21 - Would I be willing to recommend / prescribe herbal supplements / herbal medicines. 22 - Prescribing herbal medicines would require an additional effort from me 23 - I proceed as most colleagues that are a professional reference to me, regarding the prescription of HM 24 - I would prescribe herbal medicines if that was the patients’ preference. 25 - With regard to the prescription of herbal medicines I would act according to what colleagues that are a professional reference to me, thought I should perform

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ACCEPTED MANUSCRIPT Question 4 – “From the plants indicated below, check the ones you have ever recommended / prescribed:”

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Question 16 – “Of the following medicines, please indicate the ones you know and those you prescribe:”

Figure 1 - Answers to questions 4 and 16 related to knowledge of the plant and its corresponding medicinal product.

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Question 11 – “Do you ask patients if they use herbal products?”

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Question 12.1 – “In the event of possible alternative therapy with herbal medicines, do you inform the patient?”

Question 12.2 – “If you do not inform, what is the reason?” Figure 2 - Answers to questions 11, 12.1 and 12.2, referring to doctor-patient communication regarding herbal treatments.

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Figure 3 – Answers in a five-points Likert scale from totally disagree to totally agree, to the following: Question 18 (A) - "My patients would appreciate if I prescribe herbal medicines." Question 19 (B) - "I think colleagues who are a professional reference to me would appreciate if I prescribed herbal medicines." Question 24 (C) - "I would prescribe herbal medicines if that was the patients’ preference."

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Figure 4 - Answers in a 5 scale range from totally disagree to totally agree, to the following: Question 23 (A) - "I proceed as most colleagues that are a professional reference to me, regarding the prescription of herbal medicines." Question 25 (B) - "With regard to the prescription of herbal medicines I would act according to what colleagues that are a professional reference to me, thought I should perform.”

Figure 5 – Answers in a 5 scale range from totally disagree to totally agree, to the following: Question 20 (A) - "If I wanted to, I could prescribe herbal medicines because I feel with knowledge to do so." Question 21 (B) - "Would I be willing to recommend / prescribe herbal supplements / herbal medicines."

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Question 13 - “Do you consider it is important to include therapy with herbal medicinal products in medical training?”

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Question 22 - "Prescribing herbal medicines would require an additional effort from me."

Figure 6– Answers to questions 13 and 22 referring to the emphasis in what concerns training in Herbal medicine and the required effort. At the bottom, factorial analysis revealing the relationship between Use, Autonomy and Effort, namely the necessary learning effort as an important constraint underlying the use and autonomy to prescribe Herbal Medicines.

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ACCEPTED MANUSCRIPT Table 1. Main significant correlations observed. F2

Q3

Q8

Q 13

Q15

Q20

Corr

p

Corr

p

Corr

p

Corr

p

Corr

p

Corr

p

F1

0.294

0.019

0.481

<0.0001

0.418

0.001

0.518

<0.0001

0.618

<0.0001

0.700

<0.0001

F2

_

_

0.351

0.004

0.272

0.034

NS

NS

NS

0.351

Q13 Q20 Q21

_

NS

0.340*

0.022*

0.452

<0.0001

0.004

_

_

0.605

<0.0001

0.350

0.003

0.400

0.001

NS

_

_

0.388

0.001

_

_

0.697

<0.0001

_

_

_

0.251

0.047

_

_

0.378

0.001

_

_

NS

0.474

<0.0001

0.304

0.015

0.424

<0.0001

0.490

<0.0001

0.599

<0.0001

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Q3

NS

NS

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F3

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Meaning of abbreviations: Corr = correlation; p = p value; Q = Question; F1- Factor 1, Perception and Attitudes "Use" (Q12, 18, 19, 20, 21, 24);

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F2- Factor 2, Perception and Attitudes "Autonomy" (Q23 and Q25); F3- Factor 3, Perception and Attitudes "Effort" (Q22);

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Q3- Have you ever recommended / prescribed therapy with: Medicinal teas / Herbal dietary supplements / Herbal medicines / Traditional herbal medicines; Q8- Have you ever used for yourself: Medicinal herbs / Herbal dietary supplements / Herbal medicines / Traditional herbal medicines;

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Q13- Would you consider important in medical education to include therapy with herbal medicines? Q15- Would you like to go deeper in your knowledge of clinical practice with herbal medicines?

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Q20- If I wanted to, I could prescribe herbal medicines, because I feel I have the knowledge about it; Q21- I would be willing to recommend / prescribe supplements / herbal medicines * Verified only in female gender (rho correlation of Spearmen)

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ACCEPTED MANUSCRIPT Table 2. p-values obtained from mean scores comparison among some parameters. Q = question; F = Factor Female vs. Male

P values

Recommended teas

Q3

Q12

Q13

0-10 vs. 31-40

1.11 ± 0.64

1.56 ± 0.98

1.56 ± 0.67

1.33 ± 0.71

1.31 ± 0.83

1.89 ± 0.77

1.26 ± 0.76

1.07 ± 0.74

1.33 ± 0.45

p = 0.616

p = 0.004

p = 0.344

p = 0.007

p=1

1.38 ± 0.91

1.03 ± 0.92

1.56 ± 0.98

1.67 ± 0.88

1.54 ± 0.96

1.52 ± 0.99

1.78 ± 0.91

1.30 ± 0.89

1.13 ± 0.90

0.63 ± 0.48

p = 0.601

p = 0.04

p = 0.457

p = 0.021

p = 0.071

2.60 ± 1.25

2.18 ± 1.39

2.56 ± 1.01

2.38 ± 1.14

2.50 ± 1.16

1.86 ± 1.19

2.75 ± 1.04

2.32 ± 1.43

2.25 ± 1.48

1.00 ± 0.82

p = 0.026

p = 0.289

p = 0.651

p = 0.689

p = 0.016

1.05 ± 0.95

0.59 ± 0.84

0.60 ± 1.06

1.37 ± 1.00

1.31 ± 1.00

1.05 ± 1.02

2.11 ± 0.60

1.18 ± 0.94

0.76 ± 0.83

0.30 ± 0.48

p = 0,978

p < 0.0001

p = 0.056

p = 0.006

p < 0.0001

1.1 ± 0.82

0.78 ± 0.648

0.75 ± 0.77

1.32 ± 0.85

1.32 ± 0.83

1.04 ± 0.71

1.50 ± 0.72

1.28 ± 0.84

0.84 ± 0.65

0.36 ± 0.28

p = 0.007

p = 0.048

p = 0.014

p < 0.0001

0.11 ± 0.24

0.40 ± 0.38

0.70 ± 0.86

0.67 ± 0.88

0.66 ± 0.80

1.47 ± 0.79

0.74 ± 0.87

0.53 ± 0.63

0.31 ± 0.32

p = 0.835*

p < 0.0001

p = 0.185

p = 0.349

p = 0.272

1.83 ± 1.161

1.23 ± 1.032

1.46 ± 1.050

1.95 ± 1.147

1.88 ± 1.199

1.50 ± 0.889

2.50 ± 0.548

1.98 ± 1.121

1.53 ± 1.022

1.56 ± 0.882

p = 0.249

p = 0.007

p = 0.151

p = 0.098

p = 0.442

1.41 ± 0.880

1.04 ± 0.824

1.50 ± 1.160

1.65 ± 1.044

1.41 ± 1.085

1.52 ± 1.327

2.50 ± 1.517

1.33 ± 1.132

1.18 ± 1.029

1.67 ± 0.866

p = 0.659

p = 0.002

p = 0.641

p = 0.03*

p = 0.507

2.35 ± 0.974

1.96 ± 1.018

2.36 ± 1.151

2.51 ± 0.985

2.36 ± 1.036

2.19 ± 1.209

3.67 ± 0.816

2.35 ± 1.001

2.09 ± 1.083

2.33 ± 1.323

P = 0.550

p = 0.001

p = 0.982

p = 0.07

p = 0.940

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0.54 ± 0.59

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Q11

Academic degree: Specialist vs. Master

1.37 ± 0.67

p = 0.767 Q8

FHU vs. PHCU

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Never vs. Oftentimes

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F2

Years of Medical Career:

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F1

Took teas:

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Mean values comparison

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Q21

1.37 ± 0.926

2.07 ± 1.385

2.24 ± 1.206

2.00 ± 1.258

1.76 ± 1.261

3.33 ± 1.211

1.85 ± 1.159

1.66 ± 1.027

1.78 ± 1.202

p = 0.394

p = < 0.0001

p = 0.556

p = 0.027

p = 0.629

0.62 ± 0.99

0.52 ± 0.738

0.89 ± 1.05

0.77 ± 0.96

0.74 ± 0.89

0.90 ± 0.83

0.89 ± 1.269

0.63 ± 0.88

0.60 ± 0.93

1.00 ± 0.82

p = 0.250

p = 0.278

p = 0.452

p = 0.465

p = 0.573

1.53 ± 1.10

1.14 ± 1.06

1.78 ± 1.20

1.77 ± 0.93

1.55 ± 0.92

1.29 ± 0.96

2.22 ± 1.09

1.32 ± 0.99

1.03 ± 1.07

1.00 ± 0.82

p = 0.379

p = 0.012

p = 0.233

p = 0.003

p = 0.256

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Q20

2.02 ± 1.124

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Q15

Graphical Abstract

O

HO

O

O

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Carduus marianus

OCH3

3

OH

OH OH

O

Silybinin

CE

PT

Perceived need for specific knowledge in Phytotherapy by physicians

M

2

Low adherence and use of herbal medicine is confirmed in Family Medicine physicians practice

CH2OH

AC

Training in Phytotherapy is pivotal in Medical Education

Do you consider it is important to include therapy with herbal medicinal products in medical training?

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