L E Roux

L E Ven

Florent Cardiologie

Lippert Éric

Hématologie Thereaux

Christophe Jamin

Morel Immunologie

Frédéric

Cristina Hématologie Bagacean

Nathalie Kerfant

Chirurgie

Juliette Pédiatrie Ropars

Philippe Thuillier

diabète Endocrinologie

Jean-Philippe Metges

Cancérologie

Pierre Chiron Benoît

Derriennic Jérémy

Viala Jeanlin

L E Cornec

Anne-Hélène Psychologie

Lancien Frédéric

Physiologie Le Corre

Rozenn Biologie

Mignen Olivier

Physiologie Morin

BEAURUELLE Clémence Bactériologie virologie

Keywords: Electrocardiography, Arrhythmias, cardiac, Primary health care, Costs and cost analysis

Background:

The preparticipation screening before any sport is a frequent motive in general practice. The cardiovascular screening might rule out any cardiovascular pattern which can be worsened while doing sports, alongside with any potential cardiac arrhythmia at risk of sudden cardiac death (SCD). The research question for this study was: is there a cost-effectiveness analysis of performing an EKG to screen for lethal arrhythmia in primary care?

Materials and methods: The information sources were MEDLINE database via PubMed® and CENTRAL database via Cochrane Library. Keywords were defined and characterized with the preferred label of the database of Medical Subject Headings (MeSH). Research algorithms were built. Previous systematic reviews were searched. All the results found were included in the selection process. If a subpopulation from the general population was identified, the results were interpreted in the same way.

Results:

There is no study within the general population and with a high level of evidence that supports the cost-effectiveness of adding an EKG to history and physical examination to screen for lethal arrhythmia in primary care.

Discussion: Within the limits of this work and with the current lack of evidence, the recommendations from cardiology societies of realizing a large-scale EKG to screen for lethal arrhythmia, with the consequences in terms of individual input and public health costs, can be legitimately questioned.

présider le jury. J'ai découvert un espace de travail où l'on peut apprendre à faire de la recherche en médecine générale de façon simple et claire, voire drôle. Merci pour ta sympathie et ta considération envers nous pendant ces séances. Merci également pour ta disponibilité tout au long de ce travail. Sois assuré de tout mon respect.

À Madame le Docteur Marine ZAMBONINO, pour ton enthousiasme et ta passion de la médecine générale, merci infiniment d'avoir accepté d'être membre de ce jury de thèse. J'espère avoir la joie de te voir très vite à l'extérieur d'un écran.

À Monsieur le Docteur Clément COGNEAU, pour ta bienveillance et ta gentillesse pendant ces premiers jours de stage, merci à toi d'avoir accepté d'être membre de ce jury de thèse. Au plaisir de continuer à apprendre à tes côtés ce semestre.

À Monsieur Georges BEUZET, pour le temps que vous m'avez accordé.

Au Docteur Andrea MENAFOGLIO, pour la transmission si rapide de votre article et votre hâte de découvrir ce travail de thèse.

Aux Docteurs Thibault PUSZKAREK et Vincent BAUTA, pour la découverte de votre exercice qui a mis à l'épreuve ma réflexion pendant ce travail de thèse.

Aux Docteurs Thierry NEYER et Nicolas HIRTH, pour la méthode, le sens critique et les épopées gastronomiques.

Au Professeur Alice BLET, pour tes conseils qui m'ont poussée à me former le plus possible et tes prises de position pour la bleue que je suis toujours. Merci pour ta générosité en me faisant découvrir la recherche médicale dans ton domaine et en partageant ta thèse de sciences.

Au Docteur Ariane GROSS, pour ta sympathie et ta sensibilité envers tes patients et tes externes.

Au Docteur Alain SHUM CHÉONG SING, pour le partage spontané de tes connaissances et ton soutien chaleureux dès les premiers jours de cette aventure. Mention spéciale pour les wantan parties. For other sports, the content of this peculiar consultation is not legally codified. Several recommendations from different medical societies exist.

À mes co-internes

The cardiovascular screening is an important part of this consultation. The GP might rule out any cardiovascular pattern which can be worsened while doing sports, alongside with any potential cardiac arrhythmia at risk of sudden cardiac death (SCD). SCD occurs in patients supposedly free from any heart disease, during or shortly after sport. Authors define the time lapse up to 1 hour after the end of the practice, aside from any traumatic or iatrogenic etiology [START_REF] Harmon | Incidence of sudden cardiac death in athletes: A state-of-the-art review[END_REF]. Therefore, the indication of an electrocardiogram (EKG) for screening this wide population is discussed.

Among the potentially lethal cardiac arrhythmia, an EKG would be relevant for the following (4):

-long or short QT syndrome and Brugada syndrome; On the other side, the « Collège National des Généralistes Enseignants (CNGE) » took a stance in 2012 [START_REF] Cnge | Faut-il faire un ECG de repos lors de la visite de non contre-indication à la pratique du sport en compétition chez les sujets âgés de 12 à 35 ans ? Communiqué[END_REF] and 2014 [START_REF] Cnge | Visite de non contre-indication à la pratique du sport en compétition chez les sujets âgés de 12 à 35 ans : rien de nouveau depuis septembre[END_REF] to assess that a systematic EKG screening cannot be recommended due to a very high cost-effectiveness ratio. Regarding rare diseases without any consensus concerning their care and treatment once diagnosed, the specificity of the EKG was low and the scientific level of evidence of the existing studies was not high enough [START_REF] Corrado | Does Sports Activity Enhance the Risk of Sudden Death in Adolescents and Young Adults?[END_REF].

In general practice, several observational studies within the scope of french theses for the degree of doctor of medicine have looked into how GPs in different regions stick to these recommendations (9)(10)(11)(12)(13)(14)(15)(16)(17) [START_REF] Refahi | Pratique de l'électrocardiogramme lors des consultations d'aptitude sportive en compétition en médecine générale dans le sud de la Lorraine (Vosges et Meurthe-et-Moselle)[END_REF]. One thesis from 2016 wanted to determine a costeffectiveness ratio for the screening of cardiomyopathies at risk of sudden death in the young athlete in France [START_REF] Dupire | prix d'une vie : analyse médico-économique du dépistage de la mort subite chez le jeune sportif en France[END_REF].

How could it be possible to settle this question of an EKG screening on the scale of a wide population?

In terms of public health, which criteria could be taken into consideration?

Economic evaluations are a guidance in the process of making public decision. The « Haute Autorité de Santé (HAS) » published recent guidelines on this topic [START_REF] Midy | Choices in methods for economic evaluation[END_REF].

The HAS promoted 2 choices of economic evaluations which need to be supported by evidence based comparative clinical data:

-Cost-effectiveness analysis (CEA) is preferred when the health related quality of life is not a predominant concern and the outcome measured is the length of life expressed per year of life or life-years (LY) [START_REF] Houdard | L'analyse coût-efficacité[END_REF] with the all cause mortality rate as a denominator. The results are expressed with an incremental cost-effectiveness ratio (ICER) or a net monetary benefit (NMB) in monetary unit with their degree of confidence (DC);

-Cost-utility analysis (CUA) is preferred when the health related quality of life is a predominant concern and the outcome is presented with quality-adjusted life years (QALYs) [START_REF] Tessier | Fiche d'économie de la santé[END_REF].

Significant qualitative literature already exists regarding the input of an EKG for the diagnosis of potentially lethal cardiac arrhythmia in a sportive framework (23)(24)(25)(26) [START_REF] Perez | Adding an Electrocardiogram to the Pre-participation Examination in Competitive Athletes: A Systematic Review[END_REF]. The EKG is indeed sensitive to screen for any cardiac arrhythmia, but it lacks specificity to discriminate potentially lethal cardiac arrhythmia from physiological or sport induced electric changes. This lack of specificity is also correlated to the level of training of the physician reading the EKG.

The hypothesis was that quantitative data must exist to support the effectiveness of realizing an EKG to screen potentially lethal cardiac arrhythmia in primary care before sports.

The research question for this study was: is there a cost-effectiveness analysis of performing an EKG to screen for lethal arrhythmia in primary care?

MATERIALS AND METHODS

Search strategy

The protocol to realize a systematic review of literature has been standardized in guidelines called « Preferred Reporting Items for Systematic reviews and Meta-Analyses » (PRISMA). It has been written to help the construction of systematic reviews and meta-analyses by the Ottawa Hospital

Research Institute and the University of Oxford. The latest version was from 2015 [START_REF] Moher | Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement[END_REF]. A french translation [START_REF] Gedda | Traduction française des lignes directrices PRISMA pour l'écriture et la lecture des revues systématiques et des méta-analyses[END_REF] and an article from the « Société française de Santé Publique » (30) were written.

All of these guidelines and the PRISMA checklist have been the basis of this study.

The criteria used for eligibility were the presence of an ICER, NMB, a value in QALYs, or at least cost data in monetary units which could allow to calculate the economic indicators.

Because of the few studies found in the preliminary researches, no time frame was defined.

The information sources were:

-MEDLINE database via PubMed®; -CENTRAL database via Cochrane Library.

First of all, keywords were defined [START_REF] Bérard | Recherche sur PubMed[END_REF] with the help of a specialized librarian from the library of medicine of the University of Brest. The purpose was to find the appropriate terms for the research, without reducing the possibilities of results.

Each term was characterized with the preferred label of the database of Medical Subject Headings (MeSH) through the Health Terminology Ontology Portal (HeTOP) from the « Catalogue et Index des Sites Médicaux de langue Française (CiSMeF) ». Every MeSH descriptor was added individually to the search builder on PubMed®. The descriptors belonging to the same theme were linked between them and then connected to build an algorithm.

The purpose was to target the articles which related to the research question, without losing potential results depending on the words chosen by the authors. In order not to exclude the articles not indexed in MEDLINE with the MeSH terms, the same algorithm was used with the wildcard * included for title and abstract. The filter « Systematic Review » was applied with the previous algorithms on PubMed® and no result was found.

Table 2. Research algorithms on PubMed® and number of results

Research algorithms on

The Cochrane Library was researched with the same process than on PubMed®. The words from « Title Abstract Keyword » appeared with « :ti,ab,kw ». ("cost benefit analysis":ti,ab,kw OR "costs and cost analysis":ti,ab,kw) AND ("electrocardiography":ti,ab,kw OR "arrhythmia cardiac":ti,ab,kw) AND ("sports":ti,ab,kw OR "athletes":ti,ab,kw) 4 20

Selection process and data collection

All the results found were included in the selection process, that being 47 results.

The primary endpoint was the presence of an economic indicator expressed by an ICER, a NMB or a value in QALYs.

If data were available only in gross monetary units, a calculation was made to get either an ICER or NMB, either a value in QALYs depending on the type of study.

Studies were screened first by reading the title and abstract. If the primary endpoint was not matched, the conclusion was read then the entire article.

Studies within the general population were relevant for this systematic review. If there was no result within the general population but if a subpopulation from the general population was identified, the results were interpreted in the same way.

Table 4. Inclusion and exclusion criteria with their reasons

Inclusion criteria Exclusion criteria Reasons

Study

RESULTS

Figure 1 shows the selection process with a final number of 7 studies included. [START_REF] Moher | Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement[END_REF] Table 5 shows the characteristics of the included studies. The justification for their inclusion was their matching with the inclusion criteria. The level of evidence was determined following the HAS recommendations of 2013 [START_REF] Has | Niveau de preuve et gradation des recommandations de bonne pratique. État des lieux[END_REF]. The format Introduction, Methods, Results and Discussion (IMRAD) is the Gold Standard (GS) for original research articles. Within the 7 studies included, 2 studies assessed that adding a systematic EKG to history and physical examination may be cost-effective:

IDENTIFICATION

-Fuller et al. [START_REF] Fuller | Cost effectiveness analysis of screening of high school athletes for risk of sudden cardiac death[END_REF] estimated separately the cost of performing the American Heart Association (AHA) specific cardiovascular history and physical examination [START_REF] Maron | Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 Update: A scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation[END_REF] on one side and an EKG alone on the other side in high school athletes. Data from a prospective study were used for an economic modeling. Calculations were made following the HAS guidelines [START_REF] Midy | Choices in methods for economic evaluation[END_REF] to find a value of ICER and NMB. For the latter, the society's willingness to pay for a health gain of one unit in life-years or

QALYs was fixed at 50000 United States Dollar (USD) as assumed by Schoenbaum et al. [START_REF] Schoenbaum | Economic evaluation of strategies to reduce sudden cardiac death in young athletes[END_REF]. An ICER of 39980 USD per year and a NMB of 9,9 millions (M) USD were found (Appendix 2). They concluded that performance of an EKG is twice as cost effective as the AHA specific cardiovascular history and physical examination for preparticipation cardiovascular mass screening of high school athletes.

-Wheeler et al. [START_REF] Wheeler | Cost-effectiveness of preparticipation screening for prevention of sudden cardiac death in young athletes[END_REF] used a decision analysis cost-effectiveness model to project the cost and survival rates of high school athletes between 14 and 22 years old. Data from the literature were used. Comparisons of the estimated costs were made for adding an EKG to history and physical examination versus no screening at all, adding an EKG to history and physical examination versus history and physical examination alone, history and physical examination alone versus no screening at all. An ICER of 42900 USD and 61600 USD per QALY saved were found. Probabilistic sensitivity analyses were performed. They concluded that screening young athletes with EKG with 12 derivations plus cardiovascular-focused history and physical examination may be cost effective.

Two other studies assessed that adding a systematic EKG to history and physical examination may not be cost-effective:

-O'Connor et al. [START_REF] O'connor | Electrocardiogram testing during athletic preparticipation physical examinations[END_REF] estimated the total costs of performing an EKG in addition to history and physical examination and the follow-up costs for additional tests and consultations in high school athletes. Data from the literature were used for an epidemiological modeling. Data were collected depending on sex and ethnicity. An ICER of 2693 USD was found. They concluded that mass EKG screening during high school preparticipation examinations would be cost prohibitive because of a low positive predicted value of the EKG and high follow-up costs caused by lots of false-positive tests. They proposed that effectiveness of EKG screening could be improved by testing only the athletes at high risk of cardiac abnormalities known for a risk of SCD.

-Schoenbaum et al. [START_REF] Schoenbaum | Economic evaluation of strategies to reduce sudden cardiac death in young athletes[END_REF] estimated the cost for history and physical examination alone, EKG following the history and physical examination, and EKG alone, from 14 until 100 years old for potential treatment and outcomes. Data from the literature were used for a decision analysis modeling. An ICER of 37700 USD per QALY was found. Sensitivity analyses were performed.

They concluded that adding an EKG to preparticipation evaluations for athletes is not cost-effective, with costs driven by false-positive results, whereas screening based only on an EKG alone has more favorable cost-effectiveness.

One study used a different unit for their results:

-Halkin et al. [START_REF] Halkin | Preventing sudden death of athletes with electrocardiographic screening: What is the absolute benefit and how much will it cost?[END_REF] estimated the cost of a 20-year program of mandatory EKG screening for all registered competitive high school and college athletes in the USA. The estimated costs concerned the addition of an EKG to history and physical examination and the follow-up costs for additional tests and consultations. Data from the literature were used for a cost projection model. They based their calculations on the previous retrospective study from Corrado et al. (42) on which relied the ESC recommendation in 2005 ( 4). An ICER between 10,6M and 14,4M USD per life saved was found. The authors chose to express their results in USD per lives saved and not per life-year saved as they considered the cardiomyopathies progressive in nature and therefore not leading to a complete stop of exercising. This choice of a different unit makes it difficult to compare with other studies.

Two studies did not have the survival data to calculate the economic indicators needed to match the primary endpoint:

-

DISCUSSION

The main result of this systematic review is that there is no study within the general population and with a high level of evidence that supports the cost-effectiveness of adding an EKG to history and physical examination to screen for lethal arrhythmia in primary care.

The choice to focus on screening in primary care was made because the preparticipation screening before sport is a common reason for consultation in general practice. The expected results were to find experimental evidence which subtended such large-scale recommendations as the ones from the SFC (4) and the ESC (4) regarding presumed healthy persons from 12 to 35 years old.

Among the abundant literature dealing about cardiovascular screening before sport as a prevention to SCD, this systematic review shows that there are limited experimental data available. As pointed out by the CNGE in 2012 [START_REF] Cnge | Faut-il faire un ECG de repos lors de la visite de non contre-indication à la pratique du sport en compétition chez les sujets âgés de 12 à 35 ans ? Communiqué[END_REF] and 2014 [START_REF] Cnge | Visite de non contre-indication à la pratique du sport en compétition chez les sujets âgés de 12 à 35 ans : rien de nouveau depuis septembre[END_REF], the level of evidence from current clinical studies is insufficient to confirm the individual input of adding a systematic EKG to history and physical examination.

Limited resources are available to support the cost-effectiveness in terms of public health for expanding this measure to the general population. Qualitative reviews (43) (44) used mostly the results of Fuller et al. [START_REF] Fuller | Cost effectiveness analysis of screening of high school athletes for risk of sudden cardiac death[END_REF] and Wheeler et al. [START_REF] Wheeler | Cost-effectiveness of preparticipation screening for prevention of sudden cardiac death in young athletes[END_REF] which are not representative because they focused on a subgroup from the general population. Further economic evaluations seem difficult to build without solid clinical data as recommended by the HAS [START_REF] Midy | Choices in methods for economic evaluation[END_REF].

An information bias is to be considered as one limit of this systematic review was that only one person reviewed the literature and most results were in English. Some data might have been missed or misunderstood.

population might have represented a more feasible scheme for studies as athletes had mandatory medical exams. It might have been an easier subgroup to follow up in a prospective way too.

The inclusion criteria of this systematic review might be discussed, as well as the choice of the databases which were limited to the two main ones.

Some perspectives could be taken into consideration. In terms of medical research, experimental data could be collected with high power prospective randomized controlled trials within the general population. GPs and other primary care actors could be involved in the data collection and evaluation. The GS procedure could be assessed. The addition of an EKG could be evaluated in comparison with the GS in a reproducible way. As an example, the scheme could compare 2 randomized subgroups, one with the addition of an EKG to history and physical examination and the other without an EKG. The prospective follow-up could assess the occurrence of mortality due to SCD. One single effectiveness criterion could be assessed to allow economic evaluations to be conducted jointly.

Concretely, such a procedure would be difficult to achieve regarding the low rate of occurrence of SCD and the long time lapse needed before the occurrence of one event, within the general population. Current reviews estimate the incidence of documented or suspected SCD among young athletes between 1/50000 and 1/80000 athletes (3) [START_REF] Maron | Incidence and causes of sudden death in U.S. college athletes[END_REF], with different definitions of SCD and athletes depending on the studies.

Ethical considerations could also be raised regarding the realization of an EKG on a random basis for a prospective study.

The AHA took a clear stance in 2014 [START_REF] Maron | Assessment of the 12-lead electrocardiogram as a screening test for detection of cardiovascular disease in healthy general populations of young people (12-25 years of age): A scientific statement from the American Heart Association and the American College of Cardiology[END_REF] to point out that realizing a systematic EKG to a large and healthy population is not recommended because of no evidence of a significant public health benefit, despite the « tragic nature » of such an event. The AHA details the use of 14 standardized recommendations regarding personal history, family history and physical examination as a first screening tool for congenital or cardiovascular abnormalities before any further investigation.

French legislation seems to lean in this direction as a statement from May, 7 th 2021 introduces a questionnaire for athletes under 18 years old as a preparticipation screening before sport [START_REF]mai 2021 fixant le contenu du questionnaire relatif à l'état de santé du sportif mineur[END_REF]. A medical consultation is required only if the athlete and the legal representatives answered « yes » to at least one question.

In terms of clinical practice, a thesis in general practice from 2015 at the University of Brest listed the opinions of GPs in french Brittany concerning the realization of an EKG during the preparticipation consultation before sport [START_REF] Hodent | Enquête d'opinion et de pratique auprès des médecins généralistes de Bretagne sur la réalisation de l'électrocardiogramme pour la visite de non contre-indication à la pratique du sport en compétition[END_REF]. One of the result was that 31,8% of the GPs who answered the study were realizing a systematic EKG during the preparticipation consultation before sport. With this result, the author highlights the impact of recommendations issued from cardiology societies on the practice of GPs.

This systematic review demonstrated that no data proved that a systematic EKG within the general population before sport is cost-effective. Within the limits of this work, the accuracy of such recommendations with their consequences in terms of individual input and public health costs can be legitimately questioned.

CONCLUSION

This systematic review found no study within the general population and with a high level of evidence that substantiates the cost-effectiveness of adding a EKG to history and physical examination to screen for lethal arrhythmia in primary care.

There is no strong evidence that there is a benefit in performing a systematic EKG for all patients consulting in general practice for preparticipation screening before sport.

Economic evaluations are a tool to help the distribution of public health resources within a health care system. They cannot be conducted without solid clinical data [START_REF] Midy | Choices in methods for economic evaluation[END_REF].

Recommendations of the SFC (4) and the ESC (5) do apply to all patients from 12 to 35 years old.

Within the limits of this systematic review, no evidence nor effectiveness data were found in primary care. It is therefore surprising that such general recommendations were issued with this lack of evidence.

Regarding the matter of cardiovascular preparticipation screening before sport, some perspectives can be considered. With the current knowledge, targeted screening with a resting EKG with 12 derivations after a standardized history and physical examination seems to be the most beneficial strategy in terms of individual input.

Further studies are needed before recommending a universal EKG screening for lethal arrhythmia in primary care.

This work is a thesis for the degree of doctor of medicine: no funding was provided.

FIGURES AND TABLES

  Anouk, Lise, Mégane, Anaïs, Édouard, Victor, Maëva, Michael, Pauline, Timothée, Morgane et Pandora, la nouvelle famille. À Nicolas, Vanessa, Astiana, Soraya, Aurélie, Azizah et Pierre-Emmanuel, pour la mutualisation des ressources, les sous-colles, les débriefings énergiques, les pauses-café, les appels salvateurs et la RCP relecture de thèse. Malgré les distances vous êtes toujours au rendez-vous. Merci pour votre amitié formidable. À Laëtitia, la coach et la meilleure critique, pour ta présence quelles que soient les circonstances, je ne te remercierai jamais assez. À David, merci mon dalon. À Jacqueline, Marie et Michel, « L'équipe CHANE, elle gagne ! ». À Simone, « Qui veut, peut ».

-

  ventricular tachycardia; -Wolff-Parkinson-White syndrome; -dilated or hypertrophic cardiomyopathy and right ventricular arrhythmogenic cardiomyopathy. Two main medical societies recommend an EKG in the cardiovascular screening: -the « Société Française de Cardiologie (SFC) » in 2009 recommended a resting EKG with 12 derivations in addition to the medical history and the physical examination for every patient practicing a sport in competition, every 3 years from 12 years old, then every 5 years from 20 years old until 35 years old (4); -the European Society of Cardiology (ESC) in 2005 also recommended a resting EKG with 12 derivations in addition to the medical history and the physical examination from 12 to 35 years old (5).

1 ( 42 (

 142 PubMed® Number of results ("Cost-Benefit Analysis"[MeSH Terms] OR "Costs and Cost Analysis"[MeSH Terms]) AND ("Electrocardiography"[MeSH Terms] OR "arrhythmia, cardiac"[MeSH Terms]) AND ("Sports"[MeSH Terms] OR "Athletes"[MeSH Terms]) AND ("General Practice"[MeSH Terms] OR "Primary Health Care"[MeSH Terms]) "Cost-Benefit Analysis"[MeSH Terms] OR "Costs and Cost Analysis"[MeSH Terms]) AND ("Electrocardiography"[MeSH Terms] OR "arrhythmia, cardiac"[MeSH Terms]) AND ("Sports"[MeSH Terms] OR "Athletes"[MeSH Terms]) "cost benefit analysis*"[Title/Abstract] OR "costs and cost analysis*"[Title/Abstract]) AND ("electrocardiography*"[Title/Abstract] OR "arrhythmia cardiac*"[Title/Abstract]) AND ("sports*"[Title/Abstract] OR "athletes*"[Title/Abstract]) 0 A last step was to search for previous systematic reviews.

Figure 1 .

 1 Figure 1. Flow chart[START_REF] Moher | Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement[END_REF]

  Menafoglio et al. (39) estimated the cost of performing the ESC screening protocol of 2005 (5) in a population of 1070 Swiss athletes from 14 to 35 years old over 15 months between February 2011 and April 2012. In this prospective observational study, 75% of the athletes were men. Estimations only concerned the screening examinations and tests, not the follow-up costs. Original monetary units in Swiss francs (CHF) were converted in USD. -Dhutia et al. (39) estimated the total costs of interpreting an EKG in addition to history and physical examination and the follow-up costs for additional tests and consultations. In this prospective study, comparison was made between different EKG interpretation criteria. Original monetary units in Great Britain pounds (GBP) were converted in USD. Sensitivity analyses were performed.

Table 1 .

 1 Keywords

	Keywords in french	MeSH descriptor in english
	Coût-efficacité ; Coût-utilité	Cost-Benefit analysis
	Coûts et analyse des coûts	Costs and cost analysis
	Électrocardiogramme	Electrocardiography
	Troubles du rythme cardiaque	Arrhythmias, cardiac
	Médecine Générale	General practice
	Soins primaires	Primary health care
	Sports	Sports
	Athlètes	Athletes

Table 3 .

 3 Research algorithms on Cochrane Library and number of results

	Research algorithms on Cochrane Library	Number of results
	("Cost-Benefit Analysis"[MeSH Terms] OR "Costs and Cost
	Analysis"[MeSH Terms]) AND ("Electrocardiography"[MeSH Terms] OR
	"arrhythmia, cardiac"[MeSH Terms]) AND ("Sports"[MeSH Terms] OR
	"Athletes"[MeSH Terms]) AND ("General Practice"[MeSH Terms] OR
	"Primary Health Care"[MeSH Terms])

0 ("Cost-Benefit Analysis"[MeSH Terms] OR "Costs and Cost Analysis"[MeSH Terms]) AND ("Electrocardiography"[MeSH Terms] OR "arrhythmia, cardiac"[MeSH Terms]) AND ("Sports"[MeSH Terms] OR "Athletes"[MeSH Terms]) 0

Table 5 .

 5 Characteristics of the included studies

	Title			Author	Year Level of	Abstract Language Research	IMRAD
					evidence			question	format
								major
								topic
	Cost	effectiveness	Fuller et al. 2000 4	Yes	English	Yes	Yes
	analysis of screening
	of high school athletes
	for risk of sudden
	cardiac death (34)
	Electrocardiogram	O'Connor	2010 4	Yes	English	Yes	Yes
	testing during athletic	et al.
	preparticipation
	physical examinations
	(35)
	Cost-effectiveness of	Wheeler	2010 4	Yes	English	Yes	Yes
	preparticipation		et al.
	screening		for
	prevention of sudden
	cardiac death in young
	athletes (36)
	Preventing	sudden	Halkin et al. 2012 4	Yes	English	Yes	Yes
	death of athletes with
	electrocardiographic
	screening: what is the
	absolute benefit and
	how much will it cost?
	(37)
	Economic evaluation	Schoenbaum	2012 4	Yes	English	Yes	Yes
	of strategies to reduce	et al.
	sudden cardiac death
	in young athletes (38)
	Costs and yield of a	Menafoglio	2014 2	Yes	English	Yes	Yes
	15-month			et al.
	preparticipation
	cardiovascular
	examination with ECG
	in 1070 young athletes
	in	Switzerland:
	implications	for
	routine ECG screening
	(39)
	Cost Implications of	Dhutia et al. 2016 2	Yes	English	Yes	Yes
	Using	Different
	ECG Criteria	for
	Screening
	Young Athletes in the
	United Kingdom (40)

Table 1 . Keywords Table 2 .

 1Keywords2 . Flow chart Research algorithms on PubMed® and number of results

Table 3 .

 3 Research algorithms on Cochrane Library and number of results

Table 4 .

 4 Inclusion and exclusion criteria with their reasons

Table 5 .

 5 Characteristics of the included studies

	Title						Author	Year Scoring	Abstract Language Research	IMRAD	Justification
								Revue			question	format
											major
											topic
	Hjertescreening	av	unge	Stokstad	2013 4	Yes	Norwegian Yes	No	Review
	idrettsutøvere [Cardiac screening of	et al.
	young athletes]. (51)
	Recognition and significance of	Schnell	2015 2	Yes	English	Yes	Yes	Not matching
	pathological T-wave inversions in	et al.					the research
	athletes. (52)										question
	The medical value and cost-	Chevalier	2017 2	Yes	English	Yes	Yes	Not matching
	effectiveness of an exercise test for	et al.					the research
	sport preparticipation evaluation in						question
	asymptomatic middle-aged white
	male and female athletes. (53)
	Cardiovascular	evaluation	of	Menafoglio	2015 2	Yes	English	Yes	Yes	Not matching
	middle-aged individuals engaged in	et al.					the research
	high-intensity	sport	activities:						question
	implications for workload, yield
	and economic costs. (54)
	Die			kardiovaskuläre	Heinrich	2006 4	Yes	German	No	No	Review
	Voruntersuchung			im	et al.
	Wettkampfsport	[Cardiovascular
	preparticipation	screening	of
	competitive athletes]. (56)
	From	bench	to	bicycle.	Schulz	2003 4	Yes	German	No	No	Not matching
	Risikoevaluation bei Sport und	et al.					the research
	Bewegungstherapie	in	der						question
	kardiovaskulären	Primär-	und
	Sekundärprävention [From bench to
	bicycle. Risk assessment in
	connection with sports activities
	and exercise programs in the
	primary and secondary prevention
	of cardiovascular diseases]. (57)
	Systematic echocardiography is not	Riding	2015 2	Yes	English	Yes	Yes	Not matching
	efficacious when screening an	et al.					the research
	ethnically diverse cohort of athletes						question
	in West Asia. (58)
	Screening bij sporters kan acute	Panhuyzen-	2012 NC	Yes	Dutch	No	No	Part	of	a
	hartdood voorkomen [Screening of	Goedkoop					debate
	athletes prevents sudden cardiac	et al.
	death]. (59)
	Lay rescuer automated external	Berger	2004 4	Yes	English	No	No	Review
	defibrillator programs for children	et al.
	and adolescents. (60)
	The	Cost-Effectiveness	of	Janssen	2014 2	Yes	English	Yes	Yes	Not matching
	Measures to Prevent Recurrent	et al.					the research
	Ankle Sprains: Results of a 3-Arm						question
	Randomized Controlled Trial. (61)
	Sun-dried raisins are a cost-	Rietschier	2011 2	Yes	English	Yes	Yes	Not matching
	effective alternative to Sports Jelly	et al.					the research
	Beans in prolonged cycling. (62)						question
	Potential savings of a program to	Hupperets	2010 2	Yes	English	Yes	Yes	Not matching
	prevent ankle sprain recurrence:	et al.					the research
	economic	evaluation	of	a						question
	randomized controlled trial. (63)
	Preparticipation screening and	Morse	2012 4	Yes	English	No	No	Review
	prevention of sudden cardiac death	et al.
	in athletes: implications for primary
	care. (26)

« SERMENT D'HIPPOCRATE »

« Au moment d'être admise à exercer la médecine, je promets et je jure d'être fidèle aux lois de l'honneur et de la probité.

Mon premier souci sera de rétablir, de préserver ou de promouvoir la santé dans tous ses éléments, physiques et mentaux, individuels et sociaux.

Je respecterai toutes les personnes, leur autonomie et leur volonté, sans aucune discrimination selon leur état ou leurs convictions. J'interviendrai pour les protéger si elles sont affaiblies, vulnérables ou menacées dans leur intégrité ou leur dignité. Même sous la contrainte, je ne ferai pas usage de mes connaissances contre les lois de l'humanité. J'informerai les patients des décisions envisagées, de leurs raisons et de leurs conséquences. Je ne tromperai jamais leur confiance et n'exploiterai pas le pouvoir hérité des circonstances pour forcer les consciences.

Je donnerai mes soins à l'indigent et à quiconque me le demandera. Je ne me laisserai pas influencer par la soif du gain ou la recherche de la gloire.

Admise dans l'intimité des personnes, je tairai les secrets qui me seront confiés. Reçue à l'intérieur des maisons, je respecterai les secrets des foyers et ma conduite ne servira pas à corrompre les moeurs.

Je ferai tout pour soulager les souffrances. Je ne prolongerai pas abusivement les agonies. Je ne provoquerai jamais la mort délibérément.

Je préserverai l'indépendance nécessaire à l'accomplissement de ma mission. Je n'entreprendrai rien qui dépasse mes compétences. Je les entretiendrai et les perfectionnerai pour assurer au mieux les services qui me seront demandés. J'apporterai mon aide à mes confrères ainsi qu'à leurs familles dans l'adversité.

Que les hommes et mes confrères m'accordent leur estime si je suis fidèle à mes promesses ; que je sois déshonorée et méprisée si j'y manque. »

Confusion bias are also to be considered. Within the studies reviewed, the first step of the EKG interpretation was mostly considered alone. The economic impact of a positive EKG and the consequences in terms of secondary cardiovascular exams and consultations were taken into consideration only by Dhutia et al. [START_REF] Dhutia | Cost Implications of Using Different ECG Criteria for Screening Young Athletes in the United Kingdom[END_REF] in a very complete way. However, no survival data were available.

The economic indicators founded must also be weighted with some potential confounding factors.

The interpretation of an EKG was made with diagnostic criteria from cardiology societies. This interpretation was dependent on the level of experience of the physician reading the EKG. An EKG considered abnormal did not automatically lead to a diagnosis of potentially lethal arrhythmia. This good sensitivity but lack of specificity of the EKG was already described in the literature and was taken into consideration by Fuller et al. [START_REF] Fuller | Cost effectiveness analysis of screening of high school athletes for risk of sudden cardiac death[END_REF] and O'Connor et al. [START_REF] O'connor | Electrocardiogram testing during athletic preparticipation physical examinations[END_REF]. Considering the special selected population made of young athletes, it is not to be excluded that the EKG interpretation might have been influenced by the current knowledge of myocardial changes in regular athletes.

The multiplicity of units for economic indicators, as justified by Halkin et al. [START_REF] Halkin | Preventing sudden death of athletes with electrocardiographic screening: What is the absolute benefit and how much will it cost?[END_REF] made it difficult to compare with other results. The different methods chosen by the authors made it difficult also to compare the studies between them. As an example, Fuller et al. [START_REF] Fuller | Cost effectiveness analysis of screening of high school athletes for risk of sudden cardiac death[END_REF] concluded on the costeffectiveness of the EKG alone, no comparison was made between the EKG alone and the EKG in addition to history and physical examination.

Selection bias are to be considered as well. The main one was that authors focused on athletes and specifically high school athletes. The external validity of the included studies was challenged as they were not representative of the general population with different age, sex, ethnicity and level of practice who consult for cardiovascular preparticipation screening. This subgroup from the general Introduction: The preparticipation screening before any sport is a frequent motive in general practice. The cardiovascular screening might rule out any cardiovascular pattern which can be worsened while doing sports, alongside with any potential cardiac arrhythmia at risk of sudden cardiac death (SCD). The research question for this study was: is there a cost-effectiveness analysis of performing an EKG to screen for lethal arrhythmia in primary care? Materials and methods: The information sources were MEDLINE database via PubMed® and CENTRAL database via Cochrane Library. Keywords were defined and characterized with the preferred label of the database of Medical Subject Headings (MeSH). Research algorithms were built. Previous systematic reviews were searched. All the results found were included in the selection process. If a subpopulation from the general population was identified, the results were interpreted in the same way.

APPENDICES Appendix 1. Non included studies with their reasons

Results: There is no study within the general population and with a high level of evidence that supports the cost-effectiveness of adding an EKG to history and physical examination to screen for lethal arrhythmia in primary care. Discussion: Within the limits of this work and with the current lack of evidence, the recommendations from cardiology societies of realizing a large-scale EKG to screen for lethal arrhythmia, with the consequences in terms of individual input and public health costs, can be legitimately questioned.

MOTS-CLEFS