[Do general practitioners in Geneva (Switzerland) and Poitou-Charentes (France) have different approach to the management of addictions?]. / Comparaison des représentations et comportements des médecins généralistes du Canton de Genève et du Poitou-Charentes.

BACKGROUND: Addiction care is mostly provided by general practitioners (GPs) but the extent of their involvement is variable. Is this related to different training or practice contexts or to awareness campaigns? OBJECTIVE: To study GPs' views and behaviours in relation to addiction patients in different practice and training contexts and different levels of exposure to awareness campaigns. METHODS: Cross-sectional postal survey involving 526 GPs from the canton of Geneva, Switzerland, sensitized by specific addiction care campaigns, compared to 628 GPs from two rural Departments of Poitou-Charentes, France, not exposed to this type of awareness campaign. RESULTS: The response rate was 46% in Switzerland and 41% in France. The 243 responding GPs in Geneva saw as many patients with tobacco, alcohol, cannabis or opiate addiction as the 256 GPs in Poitou-Charentes. They shared similar views concerning their roles in relation to these addictions. Compared to Swiss GPs, a significantly higher number of French GPs provided first-line care for tobacco addiction. In both countries, care for addiction to other substances was mostly provided in collaboration with a specialist (>75% of cases). GPs in Geneva attributed greater importance to screening and recording of substance use. They were also more involved in training and in providing brief advice and expressed interest in the network. CONCLUSION: Awareness campaigns in Geneva could explain these differences. Sensitization of GPs to these issues may contribute to modifying certain professional attitudes, regardless of the context.

School, behavior and health-related difficulties in early adolescents with contraceptive consultation: a population-based study in eastern France.

BACKGROUND: Early adolescence (10-16 years) is a crucial period for physical, mental and cognitive development where a wide range of school, behavior and health-related difficulties may occur. These issues may be aggravated in adolescents with early affective/sexual live and contraceptive consultation. This study assessed the risk of school, behavior and health-related problems among younger boys and girls having a contraceptive consultation. Such knowledge would inform care providers about their main role in monitoring and caring adolescent problems. METHODS: This cross-sectional study included 1559 middle-school adolescents from north-eastern France (mean age 13.5±1.3). They completed a questionnaire gathering socioeconomic features, obesity, school difficulties, substances use, physical health, psychological health, social relationship, violence, sexual abuse, and suicide behaviors. Data were analyzed for each gender separately using logistic regression models. RESULTS: The contraceptive consultation concerned 6.7% of girls and 3.2% of boys (P=0.002). Based on Odds Ratio (adjusted for age, school-class level and socioeconomic factors), both boys and girls with contraceptive consultation had 2-to-7-time higher risk of consumption of alcohol, tobacco, cannabis and other drogues, poor physical health, relational problems, and perpetrated violence. Additionally, the girls had a 4-time higher risk of low academic-performance and obesity while the boys had 6-to-37-time higher risk of sexual abuse, school dropout ideation, suicide ideation and suicide attempts. CONCLUSIONS: Although based on self-reported data, we found that primary care providers play a prominent role in detecting and monitoring school, behavior and health-related problems during adolescent contraceptive consultations.

Duration of the effectiveness of nicotine electronic cigarettes on smoking cessation and reduction: Systematic review and meta-analysis.

Background: The success of pharmacotherapies for smoking cessation in real-life remains limited, with a significant number of long-term relapses. Despite first promising results, the duration of the effectiveness of electronic cigarettes is still unknown. Our objective was to assess the duration of the effectiveness of electronic cigarettes on smoking cessation and reduction in daily smokers. Methods: The databases EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and PUBMED were consulted until March 23, 2022. We selected only randomized controlled trials with daily adult smokers. The intervention was the nicotinic electronic cigarette vs. non-nicotine electronic cigarette or other validated pharmacotherapies (varenicline, bupropion and nicotine replacement therapy). The minimum duration of the intervention was 3 months, with a follow-up of at least 6 months. Two independent reviewers used the PRISMA guidelines. The primary endpoint was smoking cessation at the end of the intervention and follow-up periods confirmed by a reduction in expired CO < 10 ppm. The reduction was defined as at least 50% of the initial consumption or by a decrease of daily mean cigarette consumption at the end of the intervention and follow-up periods. Results: Abstinence at the end of the intervention and follow-up periods was significantly higher in the nicotine electronic cigarette group, compared to nicotine replacement therapy (NRT) [respectively: RR: 1.37 (CI 95%: 1.32-2.93) and RR: 1.49 (CI 95%: 1.14-1.95)] and to the non-nicotine electronic cigarette condition [respectively: RR: 1.97 (CI 95%: 1.18-2.68) and RR: 1.66 (CI 95%: 1.01-2.73)]. With regard to smoking reduction, the electronic cigarette with nicotine is significantly more effective than NRT at the end of the intervention and follow-up periods [respectively RR: 1.48 (CI 95%: 1.04-2.10) and RR: 1.47 (CI 95%: 1.18-1.82)] and non-nicotine electronic cigarette in the long term [RR: 1.31 (CI 95%: 1.02-1.68)]. Conclusions: This meta-analysis shows the duration of the effectiveness of the nicotine electronic cigarette vs. non-nicotine electronic cigarette and NRT on smoking cessation and reduction. There are still uncertainties about the risks of its long-term use and its potential role as a gateway into smoking, particularly among young people.

Perceptions, professional responsibility and management experiences of patients with alcohol, tobacco and opioid use disorder by residents in general practice and teaching general practitioners.

BACKGROUND: Substance use disorders (SUDs) are based on pathophysiological mechanisms common to all psychoactive substances. However, general practitioners (GPs) hold different views depending on the substance in question. OBJECTIVES: To determine whether the perceptions that teaching GPs and final-year residents in general practice have of patients with a SUD vary according to the substance involved and explore their professional responsibility and management experiences. METHODS: A cross-sectional observational study was carried out by asking residents and teaching GPs from eight faculties of medicine about their perceptions, professional responsibility and management experience of patients with tobacco, alcohol and opioid use disorders, using an online questionnaire between June and September 2017. RESULTS: The responses of 238 teaching GPs (mean age 50 years SD 3.5; 58% men) and 327 residents (mean age 28 years SD 9.9; 67% women) were analysed (response rates: 9 and 15% respectively). Tobacco smokers were considered to be more responsible for their acts than the other users. Teaching GPs and residents considered that it was their responsibility to discuss substance use. They did not feel able to manage alcohol and opioid use disorders. Tobacco cessation was mainly managed alone (78%). The results were quite similar among teaching GPs and residents. CONCLUSION: The majority of practitioners had no difficulty managing smoking cessation. During the management of alcohol and particularly opioid use disorders, practitioners did not feel competent. The gap between their perceived responsibility and competencies should be addressed by training and promoting collaborative care.

Adolescents consulting a GP accompanied by a third party: comparative analysis of representations and how they evolve through consultation.

BACKGROUND: Adolescents are frequently accompanied by a third party in consultation. Their stated reason for consulting is rarely psychological. However, many adolescents experience distress or impaired well-being that practitioners fail to detect. OBJECTIVES: To study the ability of adolescents to express personal concerns in general medicine consultations depending on if an accompanier is present and to explore perceptions of participants and how they evolved. METHODS: Six hundred and seventy-four adolescent consultations with 53 GPs were studied. The adolescents and any persons accompanying completed self-administered questionnaires before and after the consultation, the GPs only afterwards. Analyses compared responses before and after consultation and between participants. RESULTS: Six per cent of the adolescents were consulting for a psychological reason, but, among the others, 17% reported having personal concerns they would like to talk about. Among adolescents aged 14-17 years, those consulting alone more frequently reported personal worries but were more satisfied with the consultation than the others. A third party's presence did not appear to hinder expression for those that consulted accompanied. The representations of the third party and practitioner concerning the adolescent differed, although they tended to converge following the consultation: accompaniers overestimated the adolescents' well-being and freedom to talk, while GPs underestimated their well-being, readiness to confide and feelings of being understood. CONCLUSIONS: GPs could be more optimistic about adolescent consultations: their role is viewed more positively than they think, especially by adolescents consulting alone. The majority of adolescents wishing to say something do so, even when an accompanier is present.

Detection of adolescent suicidality in primary care: an international utility study of the bullying-insomnia-tobacco-stress test.

AIM: General practitioners (GPs) are ideally placed to identify suicidality in adolescents. However, adolescents are often reluctant to confide in their GPs about these problems, and GPs are not comfortable when questioning them about suicide. We previously proposed the BITS test, a set of four opening and four additional questions, to alert doctors about possible suicidality in an adolescent. We validated its use in the identification of suicidality ("frequent suicidal ideation or suicide attempts at one time or another)" in 15-year-old adolescents in a school setting. The objective of the present study was to assess the detection utility of this method in 13-to-18-year-olds in primary care. METHODS: We carried out a screening utility study in general practices in 17 French-speaking sites in four countries and three continents. Each GP was instructed to use the bullying, insomnia, tobacco, stress (BITS) test with five to ten 13-to-18-year-old adolescents, consulting consecutively, for any reason. They subsequently asked them questions about their suicidality. RESULTS: One hundred and two GPs tested a total of 693 adolescents; 13.0% of the adolescents (girls 15.4%, boys 9.9%) reported suicidality (1.6% known, 11.4% previously unknown). A score of at least 3 on the BITS scale was associated with suicidality (sensitivity: 65.9, specificity: 82.5%). CONCLUSIONS: The BITS test is a pragmatic instrument, alerting the GP to an adolescent's previously unknown suicidability, whatever the reason for consultation.

[Interactions between teenagers and general practitioners during consultations: progression of felt disquiet and impact of physicians' training. SOCRATE 1 study]. / Interactions adolescent-médecin généraliste en consultation. Evolution du mal-être ressenti et influence de la formation du médecin. Etude SOCRATE 1.

OBJECTIVE: This study aimed at assessing the frequency of adolescents'ill-being beyond their complaint during a general practitioner's (GP) consultation, analyzing the progression of their feeling during an ordinary consultation, comparing it to the physician's feeling and checking whether this feeling could correlate a short and specific training received by the physician. METHOD: 53 physicians were divided into 2 groups: 29 physicians experienced with adolescents and 24 control physicians from a non-adjacent department. 665 consultations involving adolescents aged 12-20 years were analyzed using 2 questionnaires filled in by adolescents before and after the consultation as well as a questionnaire filled in by physicians at the end of the consultation. RESULTS: Among adolescents consulting for "non-psychological" complaints, one out of six acknowledged having other problems. Sixty percent of them considered talking about these problems during the consultation. During a single GP's consultation, the adolescents'sensation of feeling good about themselves, being understood and listened to significantly improved. However, such an improvement did not depend on the physician's experience in adolescents. Nevertheless, experienced physicians are more circumspect than control physicians regarding the level of well-being felt or put forward by adolescents. CONCLUSION: The study reveals that a short awareness program is sufficient to sustainably draw general practitioners' attention on teenagers' disquiet, but insufficient to induce an improvement of teenagers' feeling, which is anyhow recorded during a consultation. Measuring an impact on teenagers requires a probably more thorough training for physicians and a longer-term analysis by teenagers.

Identifying teenage sexual abuse victims by questions on their daily lives.

Child sexual abuse (CSA) is an international public health problem. While general practitioners are perhaps ideally positioned to detect CSA, a lack of simple tools and their discomfort in bringing up such a sensitive subject reduce the likelihood of its being brought up and flagged in primary care. However, it may be possible to identify victims of CSA by observing its consequences on student well-being, overall well-being and risk behavior. This study investigate the predictive value of daily life events possibly associated with CSA: relationship difficulties with peers and teachers, autolytic attempts, self-mutilation, low self-esteem, addiction, poor body image, physical and psychological violence, low quality of sleep. We carried out a crosssectional survey involving a representative sample of 1719 15 year-old adolescents enrolled in 192 randomly drawn schools from two French regions. In their classrooms, they filled out a version of the Health Behavior in School-Aged Children international (HBSC) self-questionnaire. Compared to their coevals, these youth were more likely to regularly consume cannabis, OR 4.40 [1.85; 10.48] and to express fear of violence, OR 2.05 [1.28; 3,28]. They were less likely to feel satisfied about their weight, OR 2.24 [1.13; 4.40] and more likely to feel unaccepted by others, OR 1.65 [1.03; 2.65]. The C-index (concordance statistic) taking into account gender, regular cannabis consumption, fear of violence, not having the right weight and not being accepted by others, was 0.79. The C-index also including self mutilation and autolytic attempts was 0.83. Indirect thematic could likewise facilitate detection and identification of CSA.

Screening for adolescent suicidality in primary care: the bullying-insomnia-tobacco-stress test. A population-based pilot study.

AIM: Adolescents at risk for suicide often see their general practitioner solely for somatic or administrative reasons. A simple screening test given during a conversation would be of substantial help to send a signal and tackle the problem. We propose to update a screening test previously validated in France - the TSTS-Cafard - because of significant changes in the lives of adolescents with the growth of the cyber world since 2000. METHODS: The design and setting was a cross-sectional study involving 912 15-year-old adolescents in 90 French schools. They completed a questionnaire that included the TSTS-Cafard and risk factors extracted from the Health Behaviour in School-Aged Children survey. To improve the test, we selected questions drawn from the recent literature. Answers were analysed according to 'suicidality' = at least one suicide attempt in life or suicidal ideation often over the past 12 months. RESULTS: Suicidality rates were 9.6% for boys and 23.1% for girls. Although the TSTS-Cafard test was generally effective, one question was no longer discriminating. A new test, entitled 'BITS', included only four questions on bullying, insomnia, tobacco and stress, with three levels of response and scores ranging from 0 to 8. Improvement was achieved without loss of performance. Using a cut-off score of 3, we achieved 78% accuracy (area under the curve), 75% sensitivity and 70% specificity. CONCLUSION: The BITS test could allow the question of suicide risk to be addressed during a routine check-up in primary care but the results need to be validated with 13 to 18-year olds.

Are patients' pejorative representations of buprenorphine associated with their level of addiction and of misuse?

BACKGROUND: In France, buprenorphine is at once the most widely prescribed and the most commonly misused opioid maintenance treatment (OMT). Unlike other medicines, it is seldom prescribed as a generic drug. Several studies have underlined the influence of the patient's representations when choosing brand-name rather than generic forms. We aim to prove a link between these pejorative representations and misuse, a higher degree of addiction and a preference for brand-name products. METHODS: An observational study carried out at 11 sites in France using self-assessment questionnaires filled out in dispensing pharmacies by patients having come to them for buprenorphine delivery. RESULTS: Analysis was based on 806 usable questionnaires. There indeed exists a significant correlation between pejorative representations of OMT by means of buprenorphine, and a higher degree of addiction and misuse (p < .0001 for each). Preference for the brand-name product is correlated with the representation of OMT as a "trap" (p = .020). CONCLUSION: Our results underscore the existence of a link between patients' negative representations of their OMT and their drug-taking behavior. Prescribing physicians should consequently take these representations into account to more precisely identify the relevant behaviors and help their patients to evolve positively.

[To detect teenagers' suicide behaviour (I). Elaboration of a test and its validation]. / Dépister les conduites suicidaires des adolescents (I). Conception d'un test et validation de son usage.

CONTEXT: General practitioner is used to be consulted by teenagers who have already had suicide ideas or attempted suicide and who were not been taking care for. The most of the time the GP doesn't know their antecedents; but as they are at risk to do it again, it's important to detect them. OBJECTIVE: To elaborate and to validate a test to detect teenagers' suicide behaviour. METHOD: After participating to a survey (Lycoll) which included 3 872 teenagers, 17 GPs and 3 psychiatrists (ADOC) created a screening test to be used by GPs. It was a questionnaire, named TSTS, with 4 questions completed by 5 items to explore the troubles' severity. Then, this test has been experienced among 38 GPs who didn't know it before. This study has been done as a clinical audit. Each physician has been visited by a research clinical assistant who had been taught for it, to estimate the screening of suicide ideas or attempted suicide before and after taking knowledge of the test. RESULTS: Results indicate a very good acceptability of this screening tool which has been used for 60% of teenagers' office visits. It allowed to guide a large number of visits towards preoccupations which were different from the initial one and to detect suicide antecedents among 13% teenagers "tested" among whom 2/3 had already seen a GP. CONCLUSION: This test is recommended to GPs in usual practice to detect teenagers at suicide risk.

[To detect teenagers' suicide behaviour (II). Clinical audit among 40 general practitioners]. / Dépister les conduites suicidaires des adolescents (II). Audit clinique auprès de 40 généralistes.

CONTEXT: [corrected] General practitioner is used to be consulted by teenagers who have already had suicide ideas or attempted suicide and who were not been taking care for. The most of the time the GP doesn't know their antecedents; but as they are at risk to do it again, it's important to detect them. OBJECTIVE: To elaborate and to validate a test to detect teenagers' suicide behaviour. METHOD: After participating to a survey (Lycoll) which included 3 872 teen-agers, 17 GPs and 3 psychiatrists (ADOC) created a screening test to be used by GPs. It was a questionnaire, named TSTS, with 4 questions completed by 5 items to explore the troubles' severity. Then, this test has been experienced among 38 GPs who didn't know it before. This study has been done as a clinical audit. Each physician has been visited by a research clinical assistant who had been taught for it, to estimate the screening of suicide ideas or attempted suicide before and after taking knowledge of the test. RESULTS: Results indicate a very good acceptability of this screening tool which has been used for 60% of teenagers' office visits. It allowed to guide a large number of visits towards preoccupations which were different from the initial one and to detect suicide antecedents among 13% teenagers "tested" among whom 2/3 had already seen a GP. CONCLUSION: This test is recommended to GPs in usual practice to detect teen-agers at suicide risk.

Even if they are not aware of it, general practitioners improve well-being in their adolescent patients.

BACKGROUND: Most adolescents consult their general practitioner (GP) for common reasons, somatic or administrative but many of them have hidden feelings of distress. OBJECTIVES: To assess the immediate impact of 'ordinary' consultations on feelings of distress among adolescents and to compare adolescents experiencing difficulties (D) to those with no difficulties (N). To analyse how accurately GPs assess the impact of their consultation on adolescents' feelings. METHODS: GPs were randomly selected from two non-contiguous French administrative areas between April and June 2006. Fifty-three GPs gave two questionnaires to the first 10 to 15 adolescents aged 12 to 20 seen in consultation. One questionnaire was issued before the consultation and the other one afterwards. Adolescents had to position themselves about different aspects of well-being and say where they would seek help if they had problems. A GP questionnaire assessed how well they estimated their impact on the adolescent's feeling of well-being. RESULTS: Six hundred and sixty-five adolescents were assessed. They reported feeling better about their health, being able to talk, having someone to talk to or to confide in and on feeling understood. The D group (n = 147) felt significantly better compared to the N group (n = 518). GPs tended to underestimate this improvement, especially regarding adolescents in the D group feeling better about their health. CONCLUSIONS: Consulting a GP generates increased well-being among adolescents, especially for those experiencing difficulties. GPs tend to underestimate the positive impact they may have. Further studies are needed to explore if this benefit is permanent over time.

What do troubled adolescents expect from their GPs?

BACKGROUND: Adolescents often have emotional and behavioural problems that general practitioners are likely to miss. While nearly 80% of them consult their GP every year, it is usually for physical, not psychological reasons. Trust in their GPs in necessary for screening. OBJECTIVES: To identify the key quality desired by adolescents for them to feel free to confide in GPs. To determine whether this quality differed according to gender, level of at-risk behaviours or interlocutor: friend, parent or GP. METHODS: A descriptive cross-sectional study was conducted in 182 French educational institutions chosen by lot. Fifteen-year-olds completed a self-administered questionnaire under examination conditions. While the questions on behaviour were drawn from the cross-national survey entitled 'Health behaviour in school-aged children (HBSC),' the questions on conditions conducive to trust were drawn from previous studies. RESULTS: A total of 1817 (911 boys, 906 girls) questionnaires were analysed. Adolescents said they seldom confided. The main quality they expected from a GP to whom they could confide in was 'honesty', which meant ensuring secrecy, refraining from judgment, and putting forward the right questions. This priority was modified by neither gender nor experience with health-risk behaviour. The quality of 'reliability' was more closely associated with their parents or friends, while 'emotionality' was cited less often. CONCLUSION: To gain the trust of adolescents, GPs have to be sincere and non-manipulative and have the ability to ensure confidentiality and to put forward the right questions without passing judgment. Can this be verified during consultations? Prospective studies could shed light on this point.[Box: see text].

Preference for brand-name buprenorphine is related to severity of addiction among outpatients in opioid maintenance treatment.

As a form of opioid maintenance treatment, high-dose buprenorphine is increasingly being used in the United States. On the French market since 1996, it is the most commonly prescribed and frequently employed opioid maintenance treatment. For unknown reasons, the brand-name form is used far more often than the generic form (76-24%). The objective was to show that the patients' levels of addiction were differentiated according to the form of buprenorphine currently being used and to their previous experience of a different form. An observational study in 9 sites throughout France used self-assessment questionnaires filled out in retail pharmacies by all patients to whom their prescribed buprenorphine treatment was being delivered. The 151 canvassed pharmacies solicited 879 patients, of whom 724 completed the questionnaires. Participants were statistically similar to non-participants. The patients using the brand-name form subsequent to experience with the generic form exhibited a more elevated addiction severity index and a higher dosage than brand-name form users with no experience of a different form. Compared to generic users, their doses were higher, their was addiction more severe, and their alcohol consumption was more excessive; they were also more likely to make daily use of psychotropic substances. However, the level of misuse or illicit consumption was similar between these groups. Preferring the brand-name buprenorphine form to the generic form is associated with a higher level of severe addiction, a more frequent need for daily psychotropics, and excessive drinking; but the study was unable to show a causal link.

[Efficacy and security of electronic cigarette for tobacco harm reduction: Systematic review and meta-analysis]. / Efficacité et sécurité de la cigarette électronique pour la réduction du tabagisme : revue systématique et méta-analyse.

CONTEXT: Smoking is the first cause of preventable death in France and in the world. Without help, it was shown that 80 % of smokers who try to quit smoking relapse after one month with a low long-term success rate. Smoking reduction can concern smokers who did not want to quit or failed in their attempt to weaning. The final aim is to increase attractiveness of drug therapies by developing new products, such as electronic cigarettes, that can compete cigarette without reproducing its harmful effects. OBJECTIVE: Assess the capacity of electronic cigarettes to reduce or stop tobacco use among regular smokers. DATA SOURCES: Consultations MEDLINE and COCHRANE databases. KEYWORDS: e-cigarette; electronic cigarettes; ENDD (electronic nicotine delivery system); ENDS (electronic nicotine delivery device); vaping were used. TRIAL SELECTION: Randomized controlled trials (RCTs) comparing the electronic cigarette with nicotine versus placebo device. RESULTS: Two randomized controlled trials were included in the quantitative analysis. The nicotine electronic cigarette users have tobacco consumption significantly decreased compared to the placebo group (RR: 1.30, 95 % CI [1.02 to 1.66]) at 6 months. Smoking cessation rate at 3 months was greater with the electronic cigarette contains nicotine (RR: 2.55, 95 % CI [1.31 to 4.98]). LIMITS: The small number of RCTs included does not allow definitive conclusions about the effectiveness of electronic cigarettes, especially in the medium to long term. CONCLUSION: The use of electronic cigarette with nicotine decreases tobacco consumption among regular smokers. Further studies are needed to specify electronic cigarettes safety profile and its ability to cause a reduction in consumption and a long-term cessation in smokers.

[How to deal with teenagers in general practice?]. / Comment aborder l'adolescent en m'edicine g'en'erale?

Meeting a teenager as a general practitioner is not straightforward. Such a consultation has its own specific characteristics, and what is at stake goes beyond the apparent reason for the consultation. In order to avoid missing something by adopting a "wait and see" attitude in front of the uninsured teenagers, the author suggests the simplest ways of sticking to the four major objectives: ensuring self-expression, easing the relationship, improving body image and self esteem and increasing the range of possible solutions. A first series aims to expand the contents of all the consultations starting from the alleged reasons, the presence of a third party, the clinical examination and the investigative questions. A second series aims to create the conditions that help to get over a hurdle when a malaise has been diagnosed: confronting points of view, setting an appointment, strengthening the links thanks to relational tools and possibly directing towards the relevant health system.

Antifragility and Tinkering in Biology (and in Business) Flexibility Provides an Efficient Epigenetic Way to Manage Risk.

The notion of antifragility, an attribute of systems that makes them thrive under variable conditions, has recently been proposed by Nassim Taleb in a business context. This idea requires the ability of such systems to 'tinker', i.e., to creatively respond to changes in their environment. A fairly obvious example of this is natural selection-driven evolution. In this ubiquitous process, an original entity, challenged by an ever-changing environment, creates variants that evolve into novel entities. Analyzing functions that are essential during stationary-state life yield examples of entities that may be antifragile. One such example is proteins with flexible regions that can undergo functional alteration of their side residues or backbone and thus implement the tinkering that leads to antifragility. This in-built property of the cell chassis must be taken into account when considering construction of cell factories driven by engineering principles.