Emmanuel Combe

Etienne Pfister

Rémy Barré

Bruno Deffains

Jenny Lanjouw

Josh Lerner

Bruno Van Pottelsberghe

Patents against imitators : an empirical investigation on French data #

Keywords: Appropriation survey, innovation, patent, imitation Enquête Appropriation, innovation, brevet, imitation. Classification

This paper is an empirical study of the effectiveness of patents against imitators based on French survey data. We use a multinomial ordered logit and regress patent effectiveness on qualitative and quantitative variables. We find that patent costs are not a significant limitation on patent effectiveness while patent disclosure is. We also find a positive threshold effect for size. Finally, we observe many differences between the determinants of the effectiveness of product and process patents; in particular, the former is more dependant on R&D intensity and first-mover advantage while the latter is more dependent on market share, advertisement intensity and on the presence of an internal department in charge of intellectual property rights.

I. INTRODUCTION

Patents are defined as institutional tools designed to enhance the appropriation of the returns to an innovation by the innovator. By granting the innovator a supposed monopoly over the right to use and/or to sell his innovation (in exchange for the disclosure of the innovation which should reduce the risk of costly duplicative R&D efforts as well promote cumulative innovations), the patent prevents other firms, be them competitors or not, from free-riding on the innovation. The profits from innovation are thus increased and so are the incentives to innovate.

The flaw with such theoretical exposition is that patent protection against imitators is rated as imperfect in many empirical studies. Indeed, apart from a few industries, such as pharmaceuticals, where patents are held to be crucial tools of innovation appropriation, patents are often ranked to be among the least effective of all available appropriation strategies [START_REF] Levin R | Appropriating the Returns from Industrial Research and Development[END_REF], [START_REF] Cohen | Appropriability Conditions and Why Firms Patent and Why They Do Not in the American Manufacturing Sector[END_REF], [START_REF] Combe | Intellectual Property Rights Effectiveness: New Evidence from French Survey Data[END_REF]). While theoretical models have many alternative explanations, why patents are deemed imperfect appropriation tools by firms has rarely been studied in an econometric setting.

In this paper we attempt to determine the effect of selected variables on product and process patent effectiveness in the French manufacturing industry. The data used in this study are from two sources: first, a survey made by the Statistical Department of the French Ministry of Industry (SESSI) is used to gather qualitative information on patents and other appropriation tools' effectiveness as well as on patent limitations; then these data are recouped with quantitative information about the responding firms. These latter data include turnover, R&D investment, advertisement intensity and market share and are also extracted from a SESSI database.

Using an appropriate ordered logit specification, our results tend to deny the importance for patent effectiveness of deposit, renewal and enforcement costs of patents.

Instead, the disclosure induced by patents is the only significant limitation to patent effectiveness. We also find evidence of a threshold effect for size. When small firms are included in the sample, size exerts a significant positive influence on patent effectiveness; this effect disappears when only large, patenting and R&D investing firms remain in the Cahiers de la MSE -2000.01 sample. Finally, we observe many differences between process and product patent effectiveness: in the former case, advertisement intensity, market share and legal competence are important factors; in the latter case, strategies based on frequent innovation or on first mover advantage are very complementary to patent effectiveness.

The rest of the paper is organised as follows. Section 2 presents a brief survey of the previous literature on that subject. Section 3 describes the sample and our variables.

Section 4 proceeds with our empirical finding while section 5 concludes.

II. PREVIOUS LITERATURE

Studies on the effectiveness of patents in deterring imitators start with the early work of [START_REF] Scherer | Patents and the Corporation[END_REF], which indicated that U.S. patent protection is important only in a few industries such as pharmaceuticals. [START_REF] Silberston | The Economic Impact of the Patent System : a Study of the British Experience[END_REF] draw a similar conclusion from their UK study. And consistently with these early works, Mansfield [1986] showed that the pharmaceutical industry was almost the sole sector where the absence of patent protection would clearly be an important blow to innovative efforts.

These studies are based on survey data upon R&D and firm managers. So do more recent works such as [START_REF] Levin R | Appropriating the Returns from Industrial Research and Development[END_REF], [START_REF] Cohen | Appropriability Conditions and Why Firms Patent and Why They Do Not in the American Manufacturing Sector[END_REF], Brouwer and Kleinknecht [1998] and [START_REF] Combe | Intellectual Property Rights Effectiveness: New Evidence from French Survey Data[END_REF], that however include many more information on patent imperfection.

In these later studies, the inclusion of alternative appropriation mechanisms in the surveys allows to measure the relative effectiveness of patents 1 . Patents are never considered the best of the proposed appropriation mechanisms: in particular, they often rank behind strategies based on first mover-advantages, secrecy or qualified people retention. They are also rated less effective for process than for product innovation.

Although never tested, the most common explanation to this result is that the disclosure 1 Levin and al. use "patents to secure royalty income" (as opposed to "patents to prevent duplication"), "secrecy", "lead-time", "moving quickly down the learning curve" and "sales and service efforts". Cohen and al. use "secrecy", "lead-time", "complementary sales efforts", "complementary manufacturing efforts" and "product/process complexity". In their study on Dutch firms, Brouwer and Kleinknecht use "secrecy", "time lead on competitors", "keeping qualified people in the firm", "process/product complexity", "copyright and related laws", "certification and normalisation". Finally, Combe and Pfister use secrecy, first mover advantage, product/process complexity, secrecy and frequent Cahiers de la MSE -2000.01 of the innovation implied by patents is more detrimental for process innovation (that can remain in the factory) than for product innovations that are commercialised and easily accessible. Finally, patent effectiveness varies greatly across industries; it reaches its maximum in the drug industry and is lowest in textiles and in the printing industry.

These results on the ineffectiveness of patent protection against imitations can be linked with the studies on patent propensities 2 (see Brouwer and Kleinknecht [1998], [START_REF] Duguet | Appropriation strategy and the use of the patent system : an econometric analysis at the firm level[END_REF] or [START_REF] Arundel | What Percentage of Innovations Are Patented ? Empirical Estimates for European Firms[END_REF] for recent examples). All of these agree with the important role of secrecy and other means of appropriation, since a fair share of patentable innovations do not get patented 3 . Patent propensity is generally higher for product innovations than for process innovations and varies highly across industries, with the drug industry systematically displaying a high rate. [START_REF] Arundel | What Percentage of Innovations Are Patented ? Empirical Estimates for European Firms[END_REF], [START_REF] Cohen | Appropriability Conditions and Why Firms Patent and Why They Do Not in the American Manufacturing Sector[END_REF] and [START_REF] Mansfield | Patents and Innovation : an Empirical Study[END_REF] show that the propensity to patent is positively related to the effectiveness of patents against imitations (as rated by the respondents).

Theoretical models have developed many alternative explanations for patent ineffectiveness against imitators. [START_REF] Scotchmer | Novelty and Disclosure in Patent Law[END_REF], [START_REF] Choi | Dynamic R&D Competition Under Hazard Rate Uncertainty[END_REF] and [START_REF] Harter | The Propensity to Patent with Differentiated Products[END_REF] insist on the disclosure effect of patents 4 . Alternatively, [START_REF] Lerner | Patenting in the Shadow of Competitors[END_REF] and Lanjouw andLerner [1996, 1997] give theoretical and empirical evidence of the role of enforcement costs in reducing patent effectiveness. In particular, small firms may find the patents too costly to enforce. This fits well with much survey data [START_REF] Koen | Survey of Small Business Use of Intellectual Property Protection : Report of a Survey Conducted by MO-SCI Corporation for the Small Business Administration[END_REF][START_REF] Berger Consultants | The Use of Patent Protection in Europe: a Representative Survey Committed by the European Patent Office[END_REF], [START_REF] Cohen | Appropriability Conditions and Why Firms Patent and Why They Do Not in the American Manufacturing Sector[END_REF], [START_REF] Combe | Intellectual Property Rights Effectiveness: New Evidence from French Survey Data[END_REF]) as well as with patent propensity studies that often find a positive link between size and patent propensity (Brouwer and Kleinknecht [1998], [START_REF] Arundel | What Percentage of Innovations Are Patented ? Empirical Estimates for European Firms[END_REF]). However, contradictory results are obtained by [START_REF] Duguet | Appropriation strategy and the use of the patent system : an econometric analysis at the firm level[END_REF] and [START_REF] Pfister | The enforcement of intellectual property rights: an empirical study on French trademarks[END_REF]: the first study concludes that patent propensity is correlated neither with sales nor deposit and enforcement costs; in the second work, it is shown that the enforcement of trademarks, innovations. 2 Patent propensity is defined here as the percentage of innovations of a firm that gets patented. See [START_REF] Arundel | What Percentage of Innovations Are Patented ? Empirical Estimates for European Firms[END_REF] for a development on the other definitions of patent propensities. 3 Arundel & Kabla find a patent propensity rate of 36 % for product innovations and of 25 % for process innovations. [START_REF] Lerner | The Importance of Trade Secrecy: Evidence from Civil Litigation[END_REF] finds that trade secrecy disputes represent 43 % of intellectual property litigation (on a sample of 530 firms and over four and half years). 4 Disclosure of the innovation in the patent is compulsory in most patent systems.

whose process is very similar to that of patents, is independent from size or from financial strength.

Survey data also insist on the breadth of patent protection. High scope of patent protection makes imitations illegal, and this may be a sufficient deterrent to imitation. However, more often than not, firms are unsatisfied (or so they say) with the scope of their patents and complain that their innovations can be imitated around too easily [START_REF] Levin R | Appropriating the Returns from Industrial Research and Development[END_REF], [START_REF] Cohen | Appropriability Conditions and Why Firms Patent and Why They Do Not in the American Manufacturing Sector[END_REF], [START_REF] Combe | Intellectual Property Rights Effectiveness: New Evidence from French Survey Data[END_REF]). Alternatively, theoretical models such as [START_REF] Van Dijk | Patent height and competition in product improvements[END_REF] demonstrate how high patent scope can adversely affect the innovator position in technological races. Finally, [START_REF] Horstman | Patent as Information Transfer Mechanisms: To Patent or (Maybe) Not to Patent[END_REF] and [START_REF] Crampes | Information Disclosure in the Renewal of Patents[END_REF] show that firms may decide not to patent their innovations in order not to reveal any information on the profits from imitation.

III. SAMPLE AND VARIABLES

Realised in 1993, the SESSI "appropriation survey" regroups qualitative information on 1797 French firms. It was sent to a representative sample of French manufacturing firms.

Leaving out non-innovative firms leads to a sample of 1000 innovative firms. Noninnovative firms were taken out from the sample both because the reliability of their answers was questionable and because we expect them to have only scant knowledge about the patent system and other appropriation strategies. The sample of 1000 firms will then be subsequently diminished because of non-responses to particular sets of questions.

Answers to the appropriation survey are analysed in [START_REF] Combe | Intellectual Property Rights Effectiveness: New Evidence from French Survey Data[END_REF].

We first merged our sample of innovative firms from the SESSI survey with the 1993 EAE database (SESSI) and got a sample of 950 firms. Annual 1993 sales in our sample vary from 6 882 000 FF to 183 585 598 000 FF with an average of 1 321 523 220 FF.

Employment varies from 20 employees to 118 575, with an average of 1011 5 . The EAE database also enables us to compute the advertisement intensity and the market share at a three digit level. Finally, we use the Research database from the Education and Technology Ministry to gather quantitative information on R&D investments.

Our sample includes innovative firms only , but it also comprises firms that never patented an innovation. We thought important to include this type of firm because, justified or not, a major concern for policy-makers since the emergence of the so-called knowledge-based economy has been to increase the effectiveness of patents and especially to entice more firms into using this particular device. It would be a pity to bypass the firms that find patents so ineffective that they never used them. Accordingly, we regress our model on two samples. Sample 1 (average 1993 turnover: 1 084 629 020 FF) includes all data but R&D related information and internal IPP departments for both patenting and non-patenting firms. Sample 2 (average 1993 turnover: 2 432 804 800 FF) only deals with patenting firms and adds R&D related information and internal IPP departments.

We use these data to measure to measure the determinants of process and product patent effectiveness. These are ordered polytomic variables, ranging from 0 (very low effectiveness) to 4 (high effectiveness) and taken from the SESSI Appropriation survey.

As such, they reflect subjective judgements and memory of the managers. However, using similar data, [START_REF] Duguet | Appropriation strategy and the use of the patent system : an econometric analysis at the firm level[END_REF] find a strong positive correlation between the measure of patent effectiveness and that of patent propensity, thus demonstrating the relative consistency of the survey answers. We try to alleviate this problem by recouping our qualitative variables with quantitative data and by grouping some of the modalities together in unreported regressions6 .

Nine explanatory variables and fifteen industry dummies are included in the model. These are listed in Table I with a brief description of each. In the text that follows, we summarise the reasons for including these variables as well as the rationale behind any expected effect. Binary variable that takes a value of unity if secrecy is a very effective strategy to deter imitators (rating=4) and 0 otherwise (SESSI Appropriation survey) Binary variable that takes a value of unity if product/process complexity is a very effective strategy to deter imitators (rating=4) and 0 otherwise (id.) Binary variable that takes a value of unity if strategies based on frequent innovations are very effective to deter imitators (rating=4) and 0 otherwise (id.) Binary variable that takes a value of unity if strategies based on first mover advantage are very effective to deter imitators (rating=4) and 0 otherwise (id.) Binary variable that takes a value of unity if patent deposit and renewal costs are an important obstacle to patent effectiveness (rating=4) and 0 otherwise (id.) Binary variable that takes a value of unity if patent enforcement costs are an important obstacle to patent effectiveness (rating=4) and 0 otherwise (id.) Binary variable that takes a value of unity if patent disclosure is an important obstacle to patent effectiveness (rating=4) and 0 otherwise (id.) Binary variable that takes the value of 1 if the firm owns a department in charge of intellectual property rights and 0 otherwise (id.) Log of mean sales (1990-1992) (SESSI EAE database) Average market share (1990)(1991)(1992) at the four digit level (id.) Mean advertisement expenditures/sales ratio (1990-1992) (id.) Mean R&D investment/sales ratio (1990-1992) (SESSI EAE database and Research survey) Industry-specific effects, controlled by dummy variables equal to 1 if the firm belongs to one of the 15 two-digit industries, and 0 otherwise.

Note: detailed statistic description in [START_REF] Combe | Intellectual Property Rights Effectiveness: New Evidence from French Survey Data[END_REF] or available from the authors. Data on intellectual property rights departments and on R&D was available only for the subsample of patenting firms. Except for DEP, binary variables are originally ordered qualitative variable described on 5 modalities (from zero to four). The classification we made is optional and we give in the text more details about the results with alternative specifications.

Cahiers de la MSE -2000.01

The effectiveness of alternative appropriation tool (SEC, COM, FRI, FMA) captures possible interactions between patent effectiveness and these appropriation strategies. [START_REF] Cohen | Appropriability Conditions and Why Firms Patent and Why They Do Not in the American Manufacturing Sector[END_REF] find evidence that firms use the different appropriation strategies complement each other. [START_REF] Arora | Patents, Licensing and Market Structure in the Chemical Industry[END_REF] notices that in the chemical industry, patents and secrecy are simultaneously used : some components of the patented innovation are published in the patent while others are kept secret. More generally, these alternative appropriation tools render imitation more difficult (COM) or less profitable (FRI, FMA), thus increasing patent efficiency.

Patent limitations are divided into three variables (DCO, ECO and DIS) to measure the empirical relevance of models based respectively on patent costs or on patent disclosure.

So far, empirical evidence has supported the former type of limitation [START_REF] Lanjouw | The Enforcement of Intellectual Property Rights: a Survey of the Empirical Literature[END_REF]. However, deposit and enforcement costs are often proxied by size -a rather rough proxy at best. Moreover, while most studies are based on the American case, [START_REF] Combe | Intellectual Property Rights Effectiveness: New Evidence from French Survey Data[END_REF] find survey evidence that the enforcement of intellectual property rights is particularly costly in the United States and [START_REF] Pfister | The enforcement of intellectual property rights: an empirical study on French trademarks[END_REF] finds no correlation between either size or financial strength and the enforcement of trademarks.

Finally, [START_REF] Duguet | Appropriation strategy and the use of the patent system : an econometric analysis at the firm level[END_REF] show that patent deposit and enforcement costs do not seem to play any role on the patent propensity of French firms.

The presence inside the firm of a department in charge with intellectual property rights (DEP) reflects many potential effects. On one hand, these type of firms are likely to have more legal experience than others; their litigation costs are likely to be lower [START_REF] Lerner | Patenting in the Shadow of Competitors[END_REF]. On the other hand, firms that have such a department are more likely to own a department in charge with detecting the imitations, which is crucial in explaining the enforcement of trademarks [START_REF] Pfister | The enforcement of intellectual property rights: an empirical study on French trademarks[END_REF]. Because of the structure of the survey, only patenting firms were asked to answer this question.

Coming to quantitative variables, we measure the size of the firm by its sales (SAL).

Following contradictory previous results on the link between sales and patent propensity (see [START_REF] Duguet | Appropriation strategy and the use of the patent system : an econometric analysis at the firm level[END_REF] or Brouwer & Kleinknecht [1998] or [START_REF] Lerner | The Importance of Trade Secrecy: Evidence from Civil Litigation[END_REF]), our aim here is to bring new evidence on the link between sales and patent effectiveness. Indeed, size can be an essential determinant of patent effectiveness: thanks to their financial capacities, large firms shall be better able to enforce their patents through trials.

Cahiers de la MSE -2000.01

In the case of trademark, [START_REF] Pfister | The enforcement of intellectual property rights: an empirical study on French trademarks[END_REF] presents evidence that size is major determinant of whether the imitations can be easily detected. Last, large firms may deter imitation more easily thanks to their higher competitiveness. Conversely, the innovations of large firms are disseminated more broadly than those of small firms and thus face a higher risk of imitation.

Similarly, firms with a high market share (MSH) may be better able to deter imitation since imitators may simply fear to compete with these firms; market share may also be a crucial determinant in the effectiveness of lead-time strategies; and last, firms with high market share have a higher incentive to sue their infringers since the profit loss that is incurred is higher than for small firms; however, as for size, firms with large market share run the risk of being imitated more often than others because their innovations are better disseminated across the industry and thus get more coverage.

Advertisement expenses (ADV) can serve as a barrier to entry, as demonstrated by [START_REF] Bunch | Who Deters Entry ? Evidence on the Use of Strategic Entry Deterrents[END_REF] and by [START_REF] Thomas | Incumbent Firms' Response to Entry : Price, Advertising and New Product Introduction[END_REF] for the ready-to-eat cereal industry. On the other hand, innovations that are strongly advertised may be more imitated because of the high demand these advertisement expenditures generate.

We introduce the average R&D investment /sales ratio (RDS). Firms with high R&D intensity may have higher mean score for patent effectiveness because they have experience in dealing with patent mechanisms or because they can credibly threaten to introduce further innovations ; they also have an incentive to create themselves a reputation of toughness in patent enforcement ; conversely, firms with high R&D intensity innovate more and thus may be more imitated than others. Unfortunately, the available data on R&D is limited, so that we could only use them for the sub-sample of patenting firms.

Finally, to capture sector-specific effects, we use fifteen industry dummies (INDi) at the two digit level. In particular, we wish to test whether the consistently higher patent effectiveness in the pharmaceutical industry is specifically linked to that industry or to the characteristics (high R&D intensity) of the pharmaceutical firms. For the overall sample, significant industry dummies are the pharmaceutical dummy (+) and the textile dummy (-). For the patenting firms' sample, the industry specific effects are stronger, but the drug industry remains a very specific case. The sea, air and train construction industry is used as the reference.

III. EMPIRICAL FINDINGS

Cahiers de la MSE -2000.01 For the overall sample, the significant industry dummies are the drug industry (+) and the soap, perfumes and cleaning industry (-). For the patenting firms' sample, significant industry dummies include the car industry dummy and the mineral products industry. The pharmaceutical industry dummy is no longer significant.

The equations a, b and c do not control for industry effects. Therefore, we use them as a comparison to infer the biases that are likely to arise when these effects are omitted.

The coefficient of size (SAL) is positive and significant for both product and process patents effectiveness when the sample comprises patenting and non-patenting firms. It is no longer significant when we omit non-patenting firms. It remains significant though when we include various measures of patent limitations and industry-specific effects. This result tend to prove the existence of a threshold effect in size for patent effectiveness: size exerts a positive influence on patent effectiveness, but only with relatively small firms.

The influence of advertisement intensity (ADV) is more ambiguous because it is more fragile and dependent on the type of innovation. For product patents, the influence is positive but it is nor robust to the inclusion of industry specific effects or to the inclusion of first mover advantage. It is positive and more robust for process patents; however, it is no longer significant when only patenting firms are included.

The dichotomy between product and process patents is even more striking for the influence of market share (MSH). The coefficients are robust and positive for process patents, but largely insignificant for product patents. This result is another explanation of the prevalence of large firms in process innovations: [START_REF] Cohen | Firm size and the nature of innovation within industries: the case of product and process R&D[END_REF] had identified process innovations with large firms because thanks to their large production volumes, these firms reap higher profits from a given process innovation than small firms.

Here, our findings show that market share is also a crucial component of the appropriation of process innovation.

Finally, the dichotomy between process and product innovations is visible through the effects of R&D intensity (RDS). The coefficient is positive and significant for product innovations, while non-significant for process innovation. These results are robust to alternative specifications of our model.

Coming to the coefficients of the qualitative variables, we shall note that they come in support of the above dichotomy between product and process patents.

Cahiers de la MSE -2000.01

patents, slightly more so for process patents (since process innovations can more easily be kept secret than product innovations)7 .

Product and process complexity (COM) are positively related to patent effectiveness for the overall sample, but not so when non-patenting firms are excluded from the sample. This is all the more surprising that even low ratings in product or process complexity seem to have a positive and significant effect on patent effectiveness.

Strategies based on frequent innovations are complementary (FRI) to patent effectiveness for product innovation not for process innovation. It is only significant for large firms, not for the overall sample -it can even be negative, showing that high pace of innovations may diminish patent effectiveness (probably because other firms can more easily invent around the patent). This complements our results for R&D intensity.

Strategies based on first mover advantage (FMA) are complementary to patent effectiveness, but the effect is more robust for product innovation than for process innovations: the coefficient is no longer significant when non-patenting firms are excluded.

Finally, we can observe that the existence of a department in charge with intellectual property rights (DEP) is complementary to patent effectiveness for process innovations, but it is insignificant for product innovations. The most reasonable explanation for this dichotomy is that imitations are less easily detected and prosecuted when they consist in process imitations.

Coming to patent limitations, our results are straightforward. First, patent costs, whether deposit and renewal costs or enforcement costs (DCO and ECO), are never significant in explaining patent effectiveness. This contrasts with the view taken by many empirical studies based on American data (see [START_REF] Lanjouw | The Enforcement of Intellectual Property Rights: a Survey of the Empirical Literature[END_REF]), but it is consistent with the patent propensity study conducted by [START_REF] Duguet | Appropriation strategy and the use of the patent system : an econometric analysis at the firm level[END_REF] on similar data or with the results of [START_REF] Pfister | The enforcement of intellectual property rights: an empirical study on French trademarks[END_REF] on French trademarks. We may explain these differences between French and American studies on the costs allocation rule (since

We also conducted our tests on a sample composed of only the high innovation opportunities industries. Following Pavitt's [1984] classification, we omit the so-called 'supplier-dominated' industries (associated with low innovation opportunity) and focus instead on the 'science based', 'scale intensive' and 'specialised suppliers' industries (those being associated with high innovation opportunity industries)10 . For product patents, we could notice that for the overall sample advertising intensity was positively and significantly linked to product patent effectiveness even when industry specific effects were accounted for. Another modification was the disappearing of the positive influence of strategies based on frequent innovations. All other results were left unchanged. We also did a more stringent selection of high innovation opportunities industries11 . Again, for product innovations, we observe that advertising intensity seems more important than for low opportunity industries, while the role and significance of R&D intensity and strategies based on frequent innovation is lowered (in the latter case, it may even get negative). Results for process are only marginally affected: for the overall sample, disclosure and process complexity are no longer significant; results for the patenting firm sample are left unchanged.

Finally, we modified our dependent variable to account for its subjectivity. More precisely, we grouped the intermediate modalities of the patent effectiveness ratings while leaving the extreme modalities intact. With a few exceptions12 , results were unaltered.

IV. CONCLUSION more likely than others to deposit patents and to renew them for a long time; hence, these firms may be more sensitive to patent deposit and renewal costs. This possible simultaneity problem is also visible when one looks at the coefficients of the qualitative variables when all their five modalities are accounted for.

This paper sought to extend our knowledge on patent effectiveness against imitation by using Yale survey data in a logit specification. To this end, we have combined both qualitative and quantitative data to assess the empirical relevance of various firm-level variables. Our results yield several interesting features.

Size (measured by sales, financial strength or number of employees) exerts a positive influence on patent effectiveness when non-patenting firms are included in the sample; it does not when the sample consists only in patenting firms; given that the average firm size is lower in the overall sample, this could mean that there is a threshold effect on the influence of size on patent effectiveness.

This size effect is unrelated to cost-related reasons of patent limitations, such as deposit and renewal costs and/or litigation costs; neither of these turns out to be a significant limitation of patent effectiveness; in other words, reducing patent costs will not result in higher patent effectiveness against imitation and neither will it induce higher R&D investment; instead, the only significant patent limitation is patent disclosure.

Finally, we observe that the effectiveness of product patents is sensibly different from that of process patents. More precisely, secrecy is more of a substitute for process patents than for product patents; conversely, patent disclosure exerts a higher (negative) influence for product patents than for process patents. Advertisement intensity and market share are more important for process patents than for product patents while the opposite holds for first-mover advantage and for strategies based on frequent innovations; one also observes that advertising intensity plays a greater role for product patent effectiveness in the case high innovation opportunities industries than for low opportunity industries. Last, departments in charge with managing the industrial property rights portfolio exert a strong positive role for process patents, not for product patents.

TABLE I LIST

 I OF EXPLANATORY VARIABLES

	Variable	Definition
	Name
	SEC
	COM
	FRI
	FMA
	DCO
	ECO
	DIS
	DEP
	SAL
	MSH
	ADV
	RDS
	IN1;…, IN15

  Table II and table III report the maximum likelihood estimates of the parameters of the logit model for product and process patent effectiveness respectively.

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Compared to the American survey data, the average firm in our sample is of a smaller size than that in the[START_REF] Cohen | Appropriability Conditions and Why Firms Patent and Why They Do Not in the American Manufacturing Sector[END_REF] sample (mean sales of $4,44 billion and mean number of employees of 21 817). It is also smaller than the average firm in the[START_REF] Levin R | Appropriating the Returns from Industrial Research and Development[END_REF] survey, but it is likely to be larger than that in the[START_REF] Brouwer | Innovative Output and Firm's Propensity to Patent: an Exploration of a Firm's Propensity to Patent[END_REF] study, which comprises firms with less than 20 employees.Cahiers de laMSE -2000.01

That is, instead of using the five modalities separately, we group some of them (0-1; 2-3; 4; or 0; 1-2-3;4; and so on…). Unrported regressions show that the results are only marginally affected.

This effect arises even with low (2) secrecy ratings and gets stronger as the secrecy effectiveness increases.Cahiers de laMSE -2000.01

The latter group thus includes drugs, soaps and perfumes, household equipment, cars, transportation construction, mechanical equipment, electric and electronics equipment mineral products, chemicals and plastics, steel, electric and electronic components and combustibles.

This selection is based on[START_REF] Brouwer | Innovative Output and Firm's Propensity to Patent: an Exploration of a Firm's Propensity to Patent[END_REF]. High opportunity industries include drugs, cars, mechanical equipment, electric and electronic equipment, chemicals and plastics, electric and electronic components.

Advertising intensity was positive and significant for product patent effectiveness (patenting firms only). Complexity was no longer significant for process patent effectiveness (overall sample).Cahiers de laMSE -2000.01

# We are grateful to the SESSI (French Ministry of Industry) for providing us with the data. We also acknowledge the financial support from both CNRS (" Programme Les Enjeux de l'Innovation ", 5233/66) and CGP (" Programme : ", 02/1998).

in France, the losing party endorses all the administrative costs of the legal process while in the US each party endorses its own costs). [START_REF] Combe | Intellectual Property Rights Effectiveness: New Evidence from French Survey Data[END_REF] also provide survey data on higher enforcement costs in the United States than in anywhere else in the world (these higher costs are matched by higher rewards and damages).

Second, our findings highlight the role of patent disclosure as a major limitation of the private effectiveness of patents 8 . Disclosure has often been embedded in theoretical settings, but it has rarely been discussed empirically. This results provides interesting research perspectives for the design of optimal patents. Indeed, while patent length, breadth and height have been extensively looked at, the effects of disclosure on the incentive to innovate and on dynamic efficiency have rarely been integrated in models of optimal patents (Matutes & al., 1996 excepted).

In unreported regressions, we test further the robustness of our results by performing several alternative econometric specification. We replace the mean sales level (SAL) with the mean number of employees or with the mean level of internal financial capacities, both taken from the EAE database. This did not alter our results.

We also replaced our R&D intensity variable with the absolute level of R&D investment (log, taken from the "Research" dataset-SESSI); the only significant difference was that R&D was no longer significant in the product patent effectiveness equation. That R&D is not significant contrasts with the results of [START_REF] Duguet | Appropriation strategy and the use of the patent system : an econometric analysis at the firm level[END_REF], who had found a positive relationship between R&D and patent propensity. Here, our results support the view that this positive effect is mainly due to the novelty requirements: firms with high R&D budgets make innovations that are more innovative and thus more patentable.

Instead, our results show that what matters is R&D intensity.

In other unreported regressions, we also omitted all the qualitative variables based on alternative appropriation strategies. This did not change our results 9 . In another set, we excluded all quantitative variables but our results stayed robust.

8 Only high or very high ratings for disclosure will have a (negative) significant effect on patent effectiveness. 9 Only in equation (product patent/overall sample), we did observe a significant (at the 10 % level) and positive effect for the deposit and renewal costs variable, a result similar to equation 1c for product patents (see table II) and that can be explained in the following terms: firms that find patent effective are Cahiers de la MSE -2000.01


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Jean-Christophe Lagier

Pattern of infections in French and migrant homeless hospitalised at Marseille infectious disease units, France: A retrospective study, 2017-2018

Keywords: homeless, Migrants, Infectious Disease Units, tuberculosis, sexually transmitted infections, illicit drug use

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

People experiencing homelessness face numerous obstacles to accessing appropriate healthcare and frequently present at hospital with advanced disease conditions and potentially lifethreatening illness [START_REF] Chant | Critical illness in homeless persons is poorly studied: a systematic review of the literature[END_REF]. Given their lack of a secure, stable place to live, deficiencies in the quality of care and disproportionate exposure to substance and frequent alcohol consumption, homeless people may exhibit increased rates of prior acute health service use, including emergency department, hospital admissions [START_REF] Russolillo | A 10-year retrospective analysis of hospital admissions and length of stay among a cohort of homeless adults in Vancouver, Canada[END_REF][START_REF] Kushel | Factors associated with the health care utilization of homeless persons[END_REF] unplanned readmissions [START_REF] Saab | Hospital Readmissions in a Community-based Sample of Homeless Adults: a Matched-cohort Study[END_REF], prolonged hospital lengths of stay (LOS) and more costly care than those who are domiciled [START_REF] Lee | Comparison of clinical characteristics and outcomes between homeless and non-homeless patients admitted to intensive care units: An observational propensity-matched cohort study in Korea[END_REF][START_REF] Nathanson | An analysis of homeless patients in the United States requiring ICU admission[END_REF][START_REF] Bigé | Homeless Patients in the ICU: An Observational Propensity-Matched Cohort Study[END_REF][START_REF] Hwang | Hospital costs and length of stay among homeless patients admitted to medical, surgical, and psychiatric services[END_REF].

With regard to intensive care unit (ICU) admission, the demand for critical care services was higher among the homeless population compared to controls [START_REF] Oud | Characteristics, and Outcomes of ICU-Managed Homeless Patients: A Population-Based Study[END_REF]. Three recent studies from Korea (2012-2017), France (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012) and Canada (2009-2011) showed higher severity of illness, resource use, and hospital mortality of ICU-managed homeless patients compared to nonhomeless people [START_REF] Lee | Comparison of clinical characteristics and outcomes between homeless and non-homeless patients admitted to intensive care units: An observational propensity-matched cohort study in Korea[END_REF][START_REF] Bigé | Homeless Patients in the ICU: An Observational Propensity-Matched Cohort Study[END_REF][START_REF] Smith | Characteristics, clinical course, and outcomes of homeless and non-homeless patients admitted to ICU: A retrospective cohort study[END_REF]. A high rate of infectious diseases among homeless adults has been observed in many epidemiological studies [START_REF] Badiaga | Preventing and Controlling Emerging and Reemerging Transmissible Diseases in the Homeless[END_REF][START_REF] Raoult | Infections in the homeless[END_REF] and has been identified as a leading cause of increased morbidity and mortality in this community. Among hospitalised homeless people, the description of infectious disease in previous studies has primarily focused on emergency department visits [START_REF] Nathanson | An analysis of homeless patients in the United States requiring ICU admission[END_REF][START_REF] Salhi | Homelessness and Emergency Medicine: A Review of the Literature[END_REF]. In the literature, there is no research on the clinical characteristics and outcomes of IDU-managed homeless patients. Therefore, we aimed to characterize illnesses in homeless in-patients at IDUs in Marseille, France, in comparison with matched non-homeless groups as a control. We also assessed the factors having an impact on the hospital LOS.

Methods

Homeless population

Study location and patients

This was a historically retrospective study. Ethical approvals were obtained from the Marseille Institutional Review Board and Ethics Committee (Protocol: 2010-A01406-33). Use of this data is governed by Axigate access at the Assistance Publique-Hôpitaux de Marseille (APHM). The study investigated the causes, experiences, and outcomes of homeless patients hospitalised in four IDUs in one Marseille hospital (APHM), the Infectious and Tropical Diseases unit (ITD), the Chronic Diseases and Osteoarticular Infections unit (CDOI), the Acute Infectious Diseases unit (AID) where patients may stay for <72 hours after hospitalisation, and the Post-Emergency unit (PE), between 1 January 2017 and 31 December 2018. We enrolled all adults (≥ 16 years of age) who gave no address on admission and were thus labelled as homeless as described [START_REF]FEANTSA-Working Together to End Homelessness in Europe. ETHOS -European Typology on Homelessness and Housing Exclusion[END_REF] and who had an infectious disease diagnosis. Patients hospitalised only for follow-up were excluded.

Study parameters and classification of infection

We extracted from our database the following variables: socio-demographics, addictions, physical and chronic conditions, medical histories and diagnosis. A Simplified Acute Physiology Score II (SAPS) II was calculated within the first 24 hours, as recommended [START_REF] Gall | A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study[END_REF], and the length of IDU stay was recorded. Infectious disease status was confirmed through a written diagnosis from the physicians wherever possible. We excluded non-infectious diagnoses from our analytical data set. The International Classification of Diseases (ICD-10-CM, version 2019) was applied for the presence and classification of infectious disease diagnoses documented by physicians during the observation period.

Control group

Each homeless patient was randomly matched to a non-homeless patient based on the following criteria: gender, age at first admission, first admission date between 2017 and 2018 and the IDU to which the patient was admitted. Age and gender were our primary matching criteria since these are most commonly used by clinicians during the initial assessment. In the case of multiple matches within the same calendar year, those with the closest first admission date were chosen; when no match was found, the age range was broadened progressively by ±1 year. We added the year of admission to minimise the effects of temporal trends in outcomes over the course of the study, as well as the type of IDU, because diagnoses and outcomes differ substantially between the IDUs in our hospital.

Case definition

The case definition for confirmed pulmonary tuberculosis (PTB) was (i) the presence of acid-fast bacilli in the sputum, identified by real-time PCR as Mycobacterium tuberculosis complex (MTC) organisms and (ii) MTC organisms from at least one respiratory tract specimen.

Statistical analysis

Statistical analyses were performed using STATA (version 11.1). Descriptive statistics (frequency and percentages for categorical variables; mean and standard deviation for continuous variables) were used to characterise the study population. Statistical differences in baseline characteristics were evaluated using the Pearson's chi-square or Fisher's exact tests as categorical variables. The means of the quantitative data were compared using the Student's ttest. A two-tailed p-value of <0.05 was considered as statistically significant. Two regression models were developed. Only variables with a prevalence of ≥5.0% were considered for statistical analysis. Variables with p-values of <0.2 from the univariate analysis were included in the multivariable regression, which was then created by stepwise regression. Analysis of multicollinearity among the independent variables was performed using the φ coefficient to test for correlation among binary variables; and for pairs of variables that were highly correlated (absolute value of correlation coefficient >0.7), only one variable was entered into the multivariate model.

The first model (a logistic regression model) was generated to compare the distribution of potential risk factors among homeless and control groups; univariate analysis was used to examine unadjusted distributions of multiple factors (socio-demographic factors, physical and mental health status, chronic medical condition, and medical histories), symptoms or physical finding between homeless and control groups. The second model (multiple linear regressions) was applied to identify factors associated with the LOS of each admission (continuous variable).

We recorded potential risk factors (socio-demographic factors, chronic medical conditions, and medical histories) and diagnosis.

Results

General characteristics of homeless patients and controls

During the two-year study period, we enrolled 98 homeless patients including 12 women (12.4%) and 86 men (87.6%) with a mean age (± SD) of 43.3 (± 16.8) years old (range, 16-89 years) (Table 1 andTable 2). Of those, 30% were French, while the rest (70%) were migrants born in North Africa (18.9%), sub-Saharan Africa (23.3%), other European countries (22.2%), and Asia (5.6%). Eleven migrant subjects (11.8%, 10 from sub-Saharan Africa, 1 from North Africa) were found to have a complex migration route with transit through different countries ), before arrival to France. Three quarters of migrant had lived in France for less than one year before their first hospitalisation. About 83% of patients were housed in shelters or hostels while the rest (17%) had been living on the street or in their cars. One-third of this group reported frequent alcohol consumption. About 58% of patients reported smoking tobacco, with a mean 33.2±15.1 (± SD) pack-years of smoking. Among tobacco smokers, 11.4% also reported smoking cannabis. Fifteen subjects (18.5%) reported a history of drug use, including snorted drug use in nine cases (11.1%). About 18% reported a history of pulmonary tuberculosis and 14% reported suffering from hepatitis before the date of first admission. Twenty-nine percent had no health insurance and 34.3% reported language barriers. Thirteen percent were admitted to hospital by ambulance at least once over the two years. At first admission, half of these patients were admitted to the ITD, followed by the PE (23.4%), the AIT (16.3%) and the CDOI (11.2%).

Overall, there were 121 acute admissions that accounted for 1.6% of all acute admissions in the four units during the observation period. Eighty-one (66.9%) occurred in 2018 and 40 (33.1%) in 2017. Eighty-five patients (86.7%) had a single admission and 13 individuals (13.3%) had multiple admissions for different infectious disease diagnoses. Missing data (including notably socio-demographic factors, history of homelessness, symptoms) occurred in 32 people who experienced language barriers. Within the first 24 hours of admission, the mean SAPS II (±SD, min-max) score was 15.5 (±8.8, 6-62). Sixty-one percent of subjects reported at least one respiratory symptom or sign at admission with 45.9% having a cough. About 38.8% were febrile and 22.4% presented with chills. About 15.3% had skin lesions. History of diseases, other symptoms and clinical finding of homeless population are summarised in Tables 1 and2.

The 98 homeless patients were successfully matched to 98 non-homeless control patients with the same proportion of gender, age (exact match; except for eight patients who were different ±1 year), with the same period of first hospital admission (±1 month) and similar admitting IDU (p=0.8) (Table 2). We found that the numbers of acute admission per patient were similar in the two groups. Through multivariate analysis, homeless people were identified as being 22 times more likely to be migrants, 19 times more likely to report illicit drug use and three times more likely to report frequent alcohol consumption. Finally, homeless people were twice as likely to present with respiratory symptoms at admission (Table 3).

Final diagnoses (Table 4 and Supplementary Table 1)

Respiratory tract infections (other than tuberculosis) were the most common diagnosis affecting 35.7% of homeless patients (35 of 98) at least once over the two-year observation period, including community-acquired pneumonia (16.3%), followed by acute exacerbation of chronic obstructive pulmonary disease (COPD) (10.2%) and influenza-like illness (ILI). Other infections included sexually transmitted infections (20.4%), cutaneous and mucosal infections (19.4%), confirmed tuberculosis infection (12.2%), particularly PTB (10.2%), urinary tract infections (11.2%), bacteraemia (10.2%), orthopaedic infections (6%), ectoparasite infestations (6.1%), gastro-intestinal infections (6.1%), Plasmodium falciparum malaria (2.1%), systemic bartonellosis (1%) and uncomplicated varicella (1%). Overall, 83 patients (84.7%) had only one diagnosis while the remaining 15 patients (15.3%) presented with more than two diseases during the two-year study period. One homeless patient died due to pleural effusion as a complication of PTB. The overall prevalence of sexually transmitted infections and the prevalence of ectoparasite infestations were significantly higher in homeless patients than in controls while orthopaedic infections were less frequent. Infection with tuberculosis was diagnosed twice as often in homeless patients, but the difference was not statistically significant; details of each disease with the ICD-10 CM code are shown in Table 4.

Microbiological investigations performed on homeless patients revealed that, compared to controls, they were more likely to be tested for TB (80 people tested out of 98 compared to 54/98, p<10 -4 ), tested for respiratory viruses (72 respiratory specimens out of 98 compared to 37/98, p<10 -4 ), and tested for sexually transmitted infections (92 serum out of 98 compared to 70/98 p<10 -4 ). Overall, the positivity rates in tested samples were similar in the two groups (Supplementary Table 1)

Factors associated with LOS among surviving homeless people (n=97) (Table 5)

The median LOS (± SD) for each admission among the 97 surviving homeless people was 11.6 (±13.6) days and was significantly higher than in controls [5.8 (± 6.7), p<10 -4 ]. The longest hospital stay (62 days) was for one homeless patient with PTB and an Escherichia coli urinary and blood infection. The mean accumulated LOS over the two years for homeless was 19.8 (±21.0), which was significantly higher than in controls [7.4 (± 8.0), p<10 -4 ]. Using multivariate analysis, the duration of the LOS according to each IDU admission of homeless patients was significantly higher among those who reported smoking tobacco and those with a diagnosis of PTB, urinary tract infections or bacteraemia, compared to the others.

The mean duration of the LOS among homeless patients admitted with a diagnosis of tuberculosis infection, urinary tract infection or bacteraemia (n=31 admissions, 21.0±19.6 days) was significantly higher than that of controls with similar diagnoses (21 admissions, 8.9±11.6 days), p=0.008.

Treatment and outcome

Similar proportions of homeless and non-homeless patients were treated with medical treatment or surgical procedures. Homeless people were significantly more likely to receive ventilation assistance. After hospital discharge, attendance at subsequent planned consultations was significantly lower in the homeless group compared to controls. Loss of follow-up treatment occurred only in the homeless group (Table 6).

Homeless pulmonary tuberculosis diagnosis and surveillance

The screening strategy for active pulmonary tuberculosis detection based on TB symptoms or risk factors [START_REF]Systematic screening for active tuberculosis: principles and recommendations[END_REF] was applied to 80% of homeless patients during the study period. We identified a sub-population of 78 homeless patients with clinically suspected PTB (a cough for at least 3 weeks and/or haemoptysis, fever, night sweats, weight loss, or chest x-ray abnormalities) or who were at high risk (migrants, history of TB or history of contact with TB patients, HIV infection).

Ten positive cases were confirmed (of 98, 10.2%) and received TB treatment, including two rifampicin resistant cases detected by PCR. Of those, nine (of nine who were documented, 100%) were migrants being born in Algeria (three cases, 33.5%, and one of whom transited in Greece and in the Netherlands), in Mauritania (one case, 11.1%, who transited in Libya, Italia, and Germany), in Romania (two cases, 22.2%), in Pakistan (two cases, 33.3%), and in Armenia (one case, 11.1%). Four (of eight who were documented, 50%) had been residing in France for less than three months before their first hospitalisation. Of these 10 patients, four (40%) were successfully treated, three (30%) were still under treatment at the time of concluding this survey, one died with acute respiratory failure due to complications from pleural effusion and two were lost to follow-up. Of 68 patients who were negative for TB, we conducted follow-up for at least three months in 13 cases which presented with a cough lasting ≥3 weeks, abnormal CRX or CCT, or infection with HIV. Of those, six (44.1%) were attended follow-up medical consultations and seven (55.9%) were lost to follow-up.

Discussion

In our study, homeless people suffering from infectious diseases presented several risk factors for infections, including poor living conditions, migrant status, history of addiction to licit and illicit drugs, lack of health insurance coverage, and language barriers. These characteristics of homeless patients align with those previously reported in the literature in other clinical settings [START_REF] Bigé | Homeless Patients in the ICU: An Observational Propensity-Matched Cohort Study[END_REF][START_REF] Smith | Characteristics, clinical course, and outcomes of homeless and non-homeless patients admitted to ICU: A retrospective cohort study[END_REF][START_REF] Fazel | The health of homeless people in high-income countries: descriptive epidemiology, health consequences, and clinical and policy recommendations[END_REF][START_REF] Feral-Pierssens | Emergency Care for Homeless Patients: A French Multicenter Cohort Study[END_REF].

The prevalence of respiratory diseases and PTB, blood-borne and sexually transmitted infections, and skin infections still remains at high levels among homeless people [START_REF] Badiaga | Preventing and Controlling Emerging and Reemerging Transmissible Diseases in the Homeless[END_REF][START_REF] Raoult | Infections in the homeless[END_REF][START_REF] Wrezel | Respiratory infections in the homeless[END_REF][START_REF] Ly | Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015-2017: cross sectional 1-day surveys[END_REF] and varies according to living conditions. Respiratory infections, including PTB transmission, may be higher among homeless people residing in shelters due to living in rooms with other people. PTB has been reported to be frequent in the homeless population and has been extensively studied [START_REF] Beijer | Changes over time in the risk of hospitalization for physical diseases among homeless men and women in Stockholm: a comparison of two cohorts[END_REF][START_REF] Vries | Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature[END_REF]. In low TB burden countries, concentrated epidemic tends to occur among hard-to-reach groups such as migrants (who come from high TB burden countries or have disruptions in treatment during migration and on arrival in host countries) and homeless people [START_REF]Systematic screening for active tuberculosis: principles and recommendations[END_REF]. Systematic screening is recommended for such populations to ensure that active TB is detected early to help reduce TB transmission within shelters [START_REF]Systematic screening for active tuberculosis: principles and recommendations[END_REF][START_REF] Ly | Preliminary Feasibility Study of Questionnaire-based Active Pulmonary Tuberculosis Screening in Marseille Sheltered Homeless People, Winter 2018[END_REF]. Blood-borne and sexually transmitted infections among homeless people have been showed to be associated with illicit drug use and risky sexual behaviour, as well as housing in single-room hotels or with living with friends [START_REF] Badiaga | Preventing and Controlling Emerging and Reemerging Transmissible Diseases in the Homeless[END_REF]. Hepatitis B and C virus infection and respiratory diseases have been reported to be the conditions most frequently associated with deaths among homeless individuals [START_REF] Hwang | Risk factors for death in homeless adults in Boston[END_REF][START_REF] Aldridge | Morbidity and mortality in homeless individuals, prisoners, sex workers, and individuals with substance use disorders in high-income countries: a systematic review and meta-analysis[END_REF].

Secondary bacterial infections of pre-existing skin lesions may be encouraged by sleeping on the street or outdoors due to exposure to unhygienic environments and ectoparasite infestations, and arthropod-borne infections may be encouraged by exposure to animals (dogs, cats, raccoons, birds, and bats) which carry arthropods, and to human body lice [START_REF] Raoult | Infections in the homeless[END_REF][START_REF]A global brief on vector-borne diseases[END_REF]. In line with these results, the reasons for admission among homeless population in our study was disproportionately driven by respiratory infections (44.9%), including 10 cases of PTB and blood-borne and sexually transmitted infections (20.4%), with high rates of hepatitis C virus infection, HIV infection, and skin and mucosal infections (19.4%). Homeless in-patients were also significantly more likely to suffer respiratory symptoms and clinical signs, in line with previous studies conducted on homeless people living in shelters in Marseille, where a prevalence of 35-50% of respiratory symptoms was observed [START_REF] Badiaga | Preventing and Controlling Emerging and Reemerging Transmissible Diseases in the Homeless[END_REF][START_REF] Ly | Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015-2017: cross sectional 1-day surveys[END_REF]. In our survey, we identified few cases of ectoparasite infestations (6.1%) and only one case of Bartonella infection in line with a decreasing trend of body louse infestations in homeless people living in shelters in Marseille that has been observed over time [START_REF] Ly | Changing Demographics and Prevalence of Body Lice among Homeless Persons, Marseille, France[END_REF]. Importantly, we showed that homeless people had significantly longer hospital LOS for each stay compared to controls. Homeless patients admitted with TB infections, urinary tract infections and bacteraemia had a longer hospital LOS than both those with other infections, and those in the control group with similar infections.

Nathanson and colleagues showed that sepsis could prolong the hospital LOS in homeless populations compared to non-homeless patients [START_REF] Nathanson | An analysis of homeless patients in the United States requiring ICU admission[END_REF].

We noticed that homeless patients benefited from the same level of healthcare during hospitalisation when compared to controls. In particular, they did not undergo fewer diagnostic tests and did not receive less treatment. However, a lower adherence to follow-up consultations with a higher rate of "lost-to follow-up" for severe diseases (including PTB and HIV infections) was observed in the homeless population. These findings emphasise the need for health services and management systems for chronic diseases and regular clinical follow-ups for these patients, in order to effectively prevent unplanned medical admissions and lower the costs of healthcare for the homeless population. In 1992, the CDC recommended the establishment of special treatment-housing centres to provide continuous shelter, food, and treatment for homeless TB patients for the duration of their treatment [START_REF] Centers For | Prevention and control of tuberculosis among homeless persons: recommendations of the Advisory Council for the Elimination of Tuberculosis[END_REF], which could lower the loss of follow-up within such a highly mobile population.

The present study suggests that appropriate preventable measures should be implemented to protect homeless people from numerous communicable and non-communicable diseases. Access to primary care such as vaccination centres remains an important component to reducing vaccine-preventable diseases including measles-mumps-rubella, diphtheria-pertussis-tetanus and poliomyelitis, varicella and hepatitis B (notably in migrant populations from high-burden countries) [START_REF] Ravensbergen | ESGITM Working Group on Vaccination in Migrants. National approaches to the vaccination of recently arrived migrants in Europe: A comparative policy analysis across 32 European countries[END_REF]. In addition and based on our results, we recommended vaccination against influenza, invasive pneumococcal disease and Hemophilus influenzae type b and control parallelly chronic respiratory diseases and provide education to get rid of smoking in sheltered homeless people. To prevent blood or sexually transmitted diseases, distribution of free condoms, provision of oral substitutive opioid treatments and psychological follow-up, and implementation of needle-syringe distribution programs should be implemented in sheltered homeless population. Improvement of personal, clothing, and room hygiene is a major measure to prevent from skin infections and body-lice infestation. Screening for latent and active TB and parasitological infections in newly arrived migrants is also advisable [START_REF] Pontarelli | Screening for active and latent tuberculosis among asylum seekers in Italy: A retrospective cohort analysis[END_REF][START_REF] Fontanelli-Sulekova | Sanitary Bureau of the Asylum Seekers Center of Castelnuovo di Porto. Occurrence of intestinal parasites among asylum seekers in Italy: A cross-sectional study[END_REF]. Additionally, we also suggest using diagnostic set kits for most frequent infectious diseases among homeless people at hospital admission, including respiratory virus multiplex PCR testing and serological testing against sexually transmitted diseases.

Several adapted management have been literately or could be tried to better care for homeless people [START_REF] Ponka | The effectiveness of case management interventions for the homeless, vulnerably housed and persons with lived experience: A systematic review[END_REF]. The patient-centred case-management interventions may improve knowledge and self-efficacy in the context of infectious diseases that require long-term care or treatment (such as HIV, HCV and TB infection) [START_REF] Hanlon | A systematic review of interventions by healthcare professionals to improve management of noncommunicable diseases and communicable diseases requiring long-term care in adults who are homeless[END_REF]. Support housing and intensive case management (ICM) could improve adherence to antiretroviral therapy and biological outcomes among HIV-infected homeless at hospital discharge [START_REF] Kushel | Case management is associated with improved antiretroviral adherence and CD4+ cell counts in homeless and marginally housed individuals with HIV infection[END_REF][START_REF] Buchanan | The health impact of supportive housing for HIV-positive homeless patients: a randomized controlled trial[END_REF] ICM had been also shown to have a significant benefit in reducing illicit substance use and frequent alcohol consumption [START_REF] Ponka | The effectiveness of case management interventions for the homeless, vulnerably housed and persons with lived experience: A systematic review[END_REF].

Certain limitations should be noted in our study. Homeless status was determined from an administrative database that could not provide information on the duration of homelessness. The difficulty of communication due to the language barrier among migrants may bias the presence of symptoms. To some extent, the LOS may vary based on provider practice patterns rather than the severity of the condition.

In summary, the present study shows that homeless people present several risk factors for infections due to poor living conditions, migrant status, history of addiction, lack of health insurance coverage and language barriers. Compared to other patients, they present more frequently with respiratory, sexually transmitted and skin infections, including ectoparasite infestations. Hospital LOS is longer in homeless people, notably when suffering from tuberculosis infections, urinary tract infections or bacteraemia, and their adherence to follow-up consultations is lower. Therefore, homeless patients present specific demographic characteristics and patterns of infectious diseases compared to other patients and require adapted management.

With 10% of PTB being recorded in hospitalised homeless patients, this population is likely to be an important focus of contagious TB and active screening with early isolation and treatment should be initiated with efficient directly observed therapy and follow-up in order to avoid the transmission of drug susceptible and resistant TB in a developed country [START_REF] Lange | Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement[END_REF]. Shortening TB treatment by using efficient, cheap and oral drugs with few adverse events should be advocated to improve compliance with medication and survival.

(

  including Algeria and Morocco [n=1], Spain [n=1], Greece [n=1], Libya [n=3], The Netherlands [n=1], Germany [n=2] and Italia [n=5]

Table 1 . Patient characteristics.

 1

	Characteristics	Homeless	Non-homeless	Univariate analysis	p-value
		(n=98 participants)	(n=98 participants)	OR (95% CI)
	Gender			NA	1.00
	Male	86 (87.6)	86 (87.6)
	Female	12 (12.4)	12 (12.4)
	Age a (years), mean±SD, range	43.3±16.8 (16-89)	43.6±17.1 (16-88)	NA	0.92
	Birthplace, n (%)
	France	27 (30)	79 (83.2)	Ref
	Migrants	63 (70)	16 (16.8)	11.52 (5.7-23.23)	<10 -4
	North Africa	17 (18.9)	9 (9.4)
	Sub-Saharan Africa	21 (23.3)	2 (2.1)
	Europe	20 (22.2)	3 (3.1)
	Asia	5 (5.6)	2 (2.1)
	Unknown	8 (-)	3 (-)
	Mean duration of residence in France	1.1±1.5, (0-5)	NA	NA	NA
	for migrants (±SD, min-max) (years)
	Range of duration of residence in
	France for migrants (years)
	≤ 1 year	30 (73.2)
	≥ 1 years	8 (19.5)
	≥ 5 years	3 (7.3)
	Not documented	22 (-)
	Status of homelessness, n (%)		NA	NA	NA
	sheltered homeless	69 (83.1)
	unsheltered homeless living in	12 (14.4)
	the street
	unsheltered homeless living in	2 (2.4)
	their cars
	Not documented	15 (-)
	Alcohol consumption, n (%)
	Rare or never	60 (65.9)	82 (83.7)	Ref
	Frequent	31.6 (34.1)	16 (16.3)	2.64 (1.33-5.26)	<5.10 -3
	Not documented	7 (-)	0 (-)
	Smoking tobacco, n (%)	51 (58.0)	37 (37.8)	2.27 (1.26-4.46)	<6.10 -3
	Mean number of pack-years for	33.2±15.1, (10-80)	18.9±10.8, (2-40)	NA	<10 -4
	smokers (SD, min-max) (pack-years)
	Not documented	10 (-)	0 (-)
	Cannabis consummation, n (%)	10 (11.4)	7 (7.1)	1.66 (0.6-4.58)	0.32
	Illicit drug and opioid agonist	15 (18.5)	4 (4.1)	5.35 (1.69-16.9)	<10 -4
	treatment use, n (%)
	Snorting illicit substances	9 (11.1)	3 (3.1)	NA
	Injecting illicit substances	8 (9.9)	4 (4.1)	NA
	Using opioid agonist treatment	5 (6.2)	0	NA
	Not documented	17 (-)	0 (-)
	Chronic conditions and medical
	histories b , n (%)
	Previous PTB	15 (18.3)	8 (8.2)	2.51 (1.01-6.28)	0.043

Table 2 .

 2 Infectious disease unit admission data. OR, odd-ratio; CI, confidence interval; ITD, Infectious and tropical diseases; CDOI, Chronic diseases and osteoarticular infections; AID, Acute infectious diseases; PE, Post-emergency; SD, standard deviation; SAPS II, Simplified Acute Physiology Score (SAPS) II; NA, not applicable; Ref, Reference category a difficulties communicating with medical staff or loss of consciousness

	Characteristics		Homeless	Non-homeless	Univariate	p-value
				(n=98	(n=98	analysis
				participants)	participants)	OR (95% CI)
	Admission by ambulance		13/98 (13.3)	5/98 (5.1)	2.8 (0.97-8.31)	0.048
	No health assurance at first	30/98 (30.6)	3/98 (3.1)	13.9 (4.10-47.6)	<10 -4
	admission
	IDU (the first admission), n (%)				NA	0.78
		ITD	48 (49.0)	46 (47.0)
		PE	23 (23.4)	22 (22.4)
		AIT	16 (16.3)	18 (18.3)
		CDOI	11 (11.2)	12 (12.3)
	Number of acute admissions in		121	126	NA
	study period, (total) n
	Mean±SD, min-max		1.23±0.98	1.26±0.64	NA	0.66
				(1-10)	(1-4)
	Year of study					NA	0.62
		2017	40/121 (33.1)	38/126 (30.2)
		2018	81/121 (66.9)	88/126 (69.8)
	Distribution					NA	0.27
		1 admission	85 (86.7)	79 (80.6)
		2 admissions	10 (10.2)	11 (11.2)
		3 admissions	2 (2.0)	7 (7.1)
		≥4 admissions	1 (1.0)	1 (1.0)
	Language barrier a , n (%)		34 (34.7)	3 (3.1)	16.8 (4.95-57.1)	<10 -4
	SAPS II, mean±SD, min-max		15.5±8.8 (6-	14.1±8.9 (6-44)	NA	0.22
				52)
	Symptoms at admission during
	study periods
	At least one respiratory	60 (61.2)	39 (39.8)	2.38 (1.34-4.23)	0.003
	symptom
		Cough	45(45.9)	31(31.6)	NA
		Expectoration	32 (32.7)	20 (20.4)	NA
		Chest pain	24 (24.5)	15 (15.3)	NA
		Pulmonary rales	20 (20.4)	15 (15.3)	NA
		Dyspnoea	14 (19.4)	12 (12.2)	NA
		Rhinorrhoea	14 (14.3)	9 (9.2)	NA
		Haemoptysis	3 (3.1)	1 (1.0)	NA
	Acute respiratory failure	4 (4.1)	1 (1.0)	NA
	Fever	(measured	or	43 (43.9)	52 (53.1)	0.69 (0.38-7.49)	0.19
	subjective)
	Chills			22 (22.4)	14 (14.3)	1.91 (0.91-4.02)	0.09
	Night sweats		19 (20.0)	13 (13.1)	1.58 (0.72-3.39)	0.25
	Skin lesions		18 (18.4)	22 (22.9)	0.75 (0.37-1.52)	0.43
	Diarrhoea			15 (15.3)	20 (20.4)	0.70 (0.33-1.47)	0.35
	Pruritus			15 (15.3)	18 (18.4)	0.80 (0.37-1.7)	0.56
	Abdominal pain		8 (8.2)	8 (8.2)	1.00(0.35-2.78)	1.00
	Vomiting or nausea		7 (7.6)	3 (3.1)	2.43 (0.61-9.71)	0.33
	Loss of consciousness		4 4.1)	2 (2.0)	1.82 (0.32-10.2)	0.68
	Headache			4(4.1)	7 (7.1)	0.55 (0.15-1.95)	0.73
	Back pain			2 (2.0)	5 (5.1)	0.38 (0.07-2.04)	0.44

Table 3 .

 3 Multivariate logistical analysis of distribution of demographics, chronic medical conditions and clinical findings between the two groups (homeless people versus controls).

	Characteristics

Abbreviation: OR, odds-ratio; CI, confidence interval; vs, versus, TB, tuberculosis; HIV, human immunodeficiency virus.

Table 6 .

 6 Treatment and outcomes Flow chart for pulmonary tuberculosis assessment among homeless patients. Abbreviation: CRX, Chest-X Rays; PTB, pulmonary tuberculosis; COPD, Chronic Obstructive Pulmonary Disease; URTI, Upper Respiratory Tract Infection; ILI, Illness Like Infection; RIF, Rifampicin; MTB, Mycobacterium tuberculosis, HIV, Human Immunodeficiency Virus; BAL, Bronchoalveolar Lavage.

	Treatment	Homeless	Non-homeless	p-value

Acknowledgments

We are grateful to our colleagues for their help for statistic analysis.

Funding

This study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the French National Research Agency under the "Investissements d'avenir" programme [ANR-10-IAHU-03], the Région Provence Alpes Côte d'Azur and European FEDER PRIMI funding.

Potential conflicts of interest

No reported conflicts of interest.

Author Contributions Statement

TD and PG contributed to experimental design, data analysis, statistics, interpretation and writing.

VT, TL, DB, PB, JC, PP contributed to critically reviewing the manuscript. PG coordinated the work. The model provides the difference in mean LOS between the modalities of a variable. a Fitness of model F=10.7, adjusted R square=0.29, p<0.0001 b Median of the variable is used for analysis. c Including injecting illicit or snorting illicit substances or using opioid agonist treatment.

Mean duration of LOS among homeless patients admitted with at least one diagnosis tuberculosis infection, urinary tract infection or bacteraemia (n=31 admissions, 21.0±19.6 days) were likely higher than that of controls (21 admissions, 8.9±11.6 days), p=0.008.