Alice Bellicha

Aurélie Kieusseian

Anne-Marie Fontvieille

Antonio Tataranni

Hélène Charreire

Prof Jean-Michel Oppert
email: jean-michel.oppert@psl.aphp.fr

Stair-use interventions in worksites and public settings -A systematic review of effectiveness and external validity

Keywords: physical activity, stair-use interventions, worksites, public settings, point-of-decision prompts, systematic review

Objective: We performed a literature review with the main aim to propose an updated overview of the effectiveness of stair-use interventions and to determine the most effective type of intervention.

Methods: We systematically searched stair-use interventions performed in worksites or public settings, published up to mid 2013. We used a harvest plot approach to visualize the findings in addition to a quantitative synthesis. We also assessed external validity using the RE-AIM framework.

Results: Of 8,571 articles identified, 50 were included. In worksites (25 studies) and public settings (35 studies), an increase in stair climbing was found during the intervention period in 64% and 76% of studies, respectively. Combining motivational and directional signs in worksites or conducting a second intervention phase in public settings increased stair climbing in 83% and 86% of studies, respectively.

Elements of external validity were overall largely under-reported. Conclusion: There is evidence that stair-use interventions are effective to increase stair climbing in public settings, but evidence of such effect is limited in worksites. Issues regarding the best sequencing of interventions or the potential importance of environmental interventions should be addressed in future studies. Process evaluation should be an integral part of interventions.

Introduction

Increasing population physical activity (PA) level is recognized as a major public health priority (Physical Activity Guidelines Advisory Comitee, 2008). The accumulation of small bouts of PA, which can fit into daily life, has been mentioned as a strategy that may be effective to reach the recommended total level of PA (Task Force on Community [START_REF] Preventive | Recommendations to increase physical activity in communities[END_REF]. Stair climbing is one of the activities that can be easily integrated into everyday life and contribute to the accumulation of PA throughout the day. Regular stair climbing has been associated with numerous health benefits [START_REF] Boreham | Training effects of short bouts of stair climbing on cardiorespiratory fitness, blood lipids, and homocysteine in sedentary young women[END_REF][START_REF] Meyer | Stairs instead of elevators at workplace: cardioprotective effects of a pragmatic intervention[END_REF][START_REF] Meyer | Stair use for cardiovascular disease prevention[END_REF]. In sedentary women, an improvement in fitness and lipid profile was observed with an 8-week progressive stair-climbing program (40 floors a day at the end of the program) [START_REF] Boreham | Training effects of short bouts of stair climbing on cardiorespiratory fitness, blood lipids, and homocysteine in sedentary young women[END_REF]. In sedentary men, a simple 12-week intervention based on posters resulted in an increase in stair climbing (from 4.5 floors a day before the intervention to 20.6 during the intervention), an improvement of fitness, weight control, and lipid profile and a decrease of blood pressure [START_REF] Meyer | Stairs instead of elevators at workplace: cardioprotective effects of a pragmatic intervention[END_REF]. Despite those benefits, the use of stairs is still limited, as a majority of studies report a level of stair climbing compared to elevators lower than 20% [START_REF] Soler | Point-of-decision prompts to increase stair use. A systematic review update[END_REF]. Defining characteristics of effective stair-use interventions is therefore an important public health research objective.

The importance of analyzing stair use according to the setting where the intervention takes place (worksites or public settings) has been highlighted by Eves [START_REF] Eves | Point-of-decision prompts to increase stair use[END_REF]. According to this author, a median +5.9% increase in stair climbing was observed with interventions in public settings, whereas only a +0.1% increase in worksites [START_REF] Eves | Point-of-decision prompts to increase stair use[END_REF]. Since then, other studies have reported higher increases in stair climbing during interventions in worksites (Eves et al., 2012b, Lewis and Eves, 2012a, Olander and Eves, 2011a), suggesting a possible effect in this setting that remains to be more firmly established. Another important characteristic of most stair-use interventions is the use of point-ofdecision (POD) prompts (Olander and Eves, 2011b). POD prompts are signs placed close to stairwells or at the base of elevators and escalators, encouraging people to use the stairs [START_REF] Soler | Point-of-decision prompts to increase stair use. A systematic review update[END_REF]. Two recent reviews showed that POD prompts could increase stair climbing with increases ranging from +0.3 to 10.6% [START_REF] Soler | Point-of-decision prompts to increase stair use. A systematic review update[END_REF], Nocon et al., 2010). However, data in these reviews were not analyzed by setting. Therefore, a systematic updated overview of results of such intervention studies, taking into account recent papers not included in the reviews by [START_REF] Soler | Point-of-decision prompts to increase stair use. A systematic review update[END_REF] and [START_REF] Nocon | Review Article: Increasing physical activity with point-of-choice prompts--a systematic review[END_REF], and analyzing results by setting is relevant.

Several issues regarding the strategy and the type (one-phase or two-phased intervention) of stair-use interventions remain unclear. First, it is unknown whether all types of POD prompts have similar effects.

Two different types of POD prompts based on different strategies have been used: motivational signs (posters or stair-riser banners informing individuals about a health or weight loss benefit of stair climbing) and directional signs (arrows pointed to the stairs or footprints informing individuals about a nearby opportunity to use the stairs) [START_REF] Grimstvedt | Using signage to promote stair use on a university campus in hidden and visible stairwells[END_REF][START_REF] Soler | Point-of-decision prompts to increase stair use. A systematic review update[END_REF]. Their effectiveness was compared in only one study, which found a positive effect with POD prompts based on both motivational and directional signs (Lewis and Eves, 2012a). Second, the impact of repeated interventions on stair use has not been systematically evaluated in detail. Therefore, there is a need to systematically assess the literature on effects of types of POD prompts and of repeated interventions.

Finally, there is an increasing interest in the assessment of external validity (i.e. transferability), which aim is to translate research findings into practice [START_REF] Glasgow | How can we increase translation of research into practice? Types of evidence needed[END_REF]. Studies assessing the effectiveness of physical activity promotion interventions have mainly focused on internal validity, and to a lesser extent on external validity [START_REF] Vuillemin | Worksite physical activity interventions and obesity: a review of European studies (the HOPE project)[END_REF]. To our knowledge, the extent to which research has reported on elements of external validity in the field of stair-use interventions has not been examined in detail.

The first aim of this review is to propose an updated overview of the effectiveness of stair-use interventions separately in worksites and in public settings. The second aim is to determine which strategy or type of intervention appears to be the most effective. Regarding the second aim, a first hypothesis was that POD prompts based on a combination of motivational and directional signs would be more effective than POD prompts based on motivational signs only. A second hypothesis was that conducting a second intervention phase would increase stair climbing substantially more than a single intervention phase. The third aim is to evaluate how elements of external validity had been assessed and reported. Our hypothesis was that only few studies had reported such element.

Material and methods

Literature search, selection of studies and data extraction

The literature search was performed in June 2013, using three electronic databases (PubMed, Web of Science and Cochrane Library). The reference sections of the included articles were also reviewed and a search based on the first author of the articles was carried out. Figure 1 presents the flow chart of the systematic literature search. The search was limited to English language articles. It was conducted using combinations of the following keywords: 'stair intervention' OR 'stair climbing' OR 'stair use' OR 'pointof-decision' OR 'point-of-choice' OR 'worksite AND stair' OR 'public setting AND stair' OR 'prompts AND stair'. The initial inclusion criterion was the implementation of stair-use interventions. We included studies only if 1) interventions were implemented in worksites or in public settings, 2) the alternative to stairs was an elevator or an escalator, 3) stair use or stair climbing was measured before and during the interventions (e.g. when prompts were still present); studies measuring stair use only before and after the interventions (e.g. when prompts had been removed), were therefore excluded, 4) stair use or stair climbing was expressed as a percentage relative to the use of escalator or elevator. The same inclusion criteria were used for the 3 objectives of our review. All studies published as of the date of the search were included.

The characteristics of each included article were extracted by one reviewer (AB) and checked by a second reviewer (JMO), and included: authors, journal, year of publication, country, setting, alternative to stairs, main outcome, assessment tools, duration and description of interventions.

Quality assessment

The quality of included studies was assessed with a standardized quality assessment tool, the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies 2003 (Thomas et al., 2004, www.ephpp.ca/tools.htlm), which has been developed to evaluate both randomized and nonrandomized studies [START_REF] Deeks | Evaluating nonrandomised intervention studies[END_REF]. This tool estimates a global rating of study quality using six components which can be rated as 'strong', 'moderate' or 'weak': A) selection bias, B) study design, C) confounders, D) blinding, E) data collection methods, F) withdrawals and drop-outs. The global rating defined the study quality as strong if no component was rated as weak, moderate if one component was rated as weak and weak if two or more components were rated as weak (Thomas, 2004). In order to adapt the tool to our research question, we excluded components A and F from the analysis because they were not found applicable to the study design of included studies. The estimation of the global rating, based on the 4 relevant dimensions that we selected in our study, however, was unchanged.

Quality of each included study was assessed by one reviewer (AB) and checked by a second reviewer (JMO). When opinions differed, consensus on ratings was reached through discussion.

Assessment of effectiveness

We reported the percentages of stair use (defined as the action of going up or down the stairs) or stair climbing (defined as the action of going up the stairs) for all the study phases: during baseline (preintervention), intervention (first and second phase) and follow-up (post-intervention) periods when results were available. For studies with multiple post-intervention data collection, we reported the last measurement (after the end of the intervention). When an intervention was conducted in more than one location, we reported the result obtained for each location. In some studies, stair use was reported only for specific socio-demographic subgroups (e.g. according to sex, age or ethnicity). In this case, we calculated the mean percentage of stair use of the subgroups as described by [START_REF] Soler | Point-of-decision prompts to increase stair use. A systematic review update[END_REF]Dolan et al. (Dolan et al., 2006, Soler et al., 2010). We therefore reported only one percentage of stair use per study and per location. For each study phase, we converted the results into absolute and relative change and we calculated an overall median change for both absolute and relative change (the calculation method followed the one presented by [START_REF] Soler | Point-of-decision prompts to increase stair use. A systematic review update[END_REF]. Then, based on the results of the study arms, we estimated the overall effectiveness for each study [START_REF] Van Cauwenberghe | Effectiveness of school-based interventions in Europe to promote healthy nutrition in children and adolescents: systematic review of published and 'grey' literature[END_REF]. The overall result was considered an improvement if an increase in stair use was found in at least one study arm and no decrease was found, 2) a deterioration if a decrease in stair use was found in at least one study arm and no increase was found, 3) mixed if an increase and a decrease in stair use was found in at least one study arm, 4) no change if no significant change in any direction was found in any location.

The number of studies included in the analysis varied according to the research question.

Effectiveness of all stair-use interventions: we selected all types of stair-use interventions (based on POD prompts, social approaches and stairwell enhancements) and we reported both the results of the first phase and follow-up period of the intervention.

Comparison between different types of POD prompts (motivational and/or directional signs): we selected studies conducted in worksites only (interventions with directional signs have not yet been performed in public settings) and we reported results for the first intervention phase.

Effectiveness of repeated exposure to interventions: we selected studies conducted in worksites and in train stations and excluded studies conducted in other public settings such as malls or airports (it can be hypothesized that shoppers or travelers do not visit the same malls or airports on a regular basis, and that a majority of persons exposed, for example, to the second intervention phase have not been exposed to the first phase [START_REF] Boen | A simple health sign increases stair use in a shopping mall and two train stations in Flanders, Belgium[END_REF]). We reported both the results of the first and the second intervention phase.

Synthesis of findings

We used a harvest plot approach developed by Ogilvie and colleagues (Barnett et al., 2012[START_REF] Ogilvie | The harvest plot: a method for synthesising evidence about the differential effects of interventions[END_REF] to visualize the findings for the first and second aims of the study (updated overview of effectiveness of stair-use interventions, identification of most effective strategy, respectively). This approach allows a graphic presentation of findings which takes into account study quality, sample size and effectiveness of interventions. A hypothesis-testing approach was adopted, comparing the null

External validity: RE-AIM framework

RE-AIM is a five-step framework designed to help translate research findings into practice and policy [START_REF] Glasgow | Evaluating the public health impact of health promotion interventions: the RE-AIM framework[END_REF]. This framework has been used in a number of prevention research fields including obesity prevention [START_REF] Klesges | Review of external validity reporting in childhood obesity prevention research[END_REF][START_REF] Vuillemin | Worksite physical activity interventions and obesity: a review of European studies (the HOPE project)[END_REF]. Our analysis was based on the 5 following criteria: 1) Reach measures participation at the individual level (e.g. participation rate and representativeness of individuals), 2) Efficacy refers to the impact on selected outcomes (e.g. whether outcomes were compared to a standard goal, whether adverse effects were reported), 3) Adoption measures the proportion and representativeness of settings and staff members adopting a given program (e.g. participation rate and representativeness of settings), 4) Implementation is the extent to which a program is delivered as intended (e.g. staff expertise or training, consistency of delivery), 5) Maintenance refers to the long-term change at both the individual and setting level (e.g. which components are institutionalized or modified over time after the end of the intervention). The percentage of studies that used the respective external validity criteria was reported.

Results

Study characteristics and quality

Of the 8,571 articles initially identified, 50 were included in our review (Figure 1). In five articles, 2 distinct studies were performed, in one article 3 distinct studies were performed and in one article 4 distinct studies were performed (studies were considered distinct when different interventions were conducted in different locations or when different outcomes were measured, i.e. stair use or stair climbing). Sixty studies were therefore included. Sixty, 29 and 60 studies have been used to investigate the first, second and third aim of the study, respectively. The main characteristics of these studies are presented in Table 1 where studies are listed alphabetically according to setting (worksites then public settings). Twentyfive studies were conducted in worksites and 35 in public settings such as train station or shopping mall.

The studies were conducted in different countries, with a majority of studies from the United Kingdom and the United States (28 in the UK, 18 in the USA, 3 in Belgium, 2 in Australia, China, Netherlands, and 1 in Denmark, Germany, Japan, South Africa and Spain). Study quality was rated as strong, moderate and weak in 0, 22 and 38 studies, respectively (summary results of quality assessment are shown in Table 2 and detailed results of quality assessment of included studies are shown in Supplementary Table 1). Less than half of reviewed studies (23 of 60 studies) included measurements during a follow-up period after the intervention. Only 1 study evaluated long-term effectiveness during follow-up (at least six months after the end of the intervention).

Duration of the interventions ranged from 1 day [START_REF] Andersen | Prompting health professionals to be activity role models--motivating stair use at the 2001 ACSM scientific meeting[END_REF] to 16 weeks (Lewis and Eves, 2012c). Interventions were either designed as single (36 studies) two phases (24 studies) and were conducted in one or several locations. Each phase of the interventions and each result of different locations were considered as a study arm. Therefore, in the 50 articles included in our review, 94 study arms were identified. During the first intervention phase, POD prompts strategy was used alone in 63 study arms (motivational signs in 56 study arms, and supplemented by directional signs in 7 study arms).

Stairwell enhancements (e.g. artwork and music or painting in the stairwell) and interventions based on social approaches (e.g. promotion days, behavioral modeling or e-mails sent by the worksite's doctor), alone or in addition of POD prompts, were both conducted in 3 study arms. During the second intervention phase, POD prompts, stairwell enhancements and social approaches were used in respectively 22, 1 and 2 study arms.

The main outcome was stair climbing in 48 studies and stair use (ascent and descent combined) in 12 studies, 11 of these in worksites. The alternative to stairs was always an elevator in worksites and an escalator in public settings. Stair use was measured by observers in 50 studies, by automatic counters in 6 studies, by a combination of camera and observer in 3 studies and by an interviewer in 1 study.

Effectiveness of interventions

In studies conducted in worksites, stair use and stair climbing ranged during the baseline period from 11.1% to 69.0% and from 19.0% to 59.4%, respectively. The calculated mean stair use and stair climbing were of 30.7% and 37.4%, respectively. In studies conducted in public settings, stair climbing ranged from 1.7% to 41.9% during the baseline period, with a mean stair climbing of 16.4% (Supplementary Table 2). During the intervention period of all studies, an increase in stair climbing was found in 64% of studies in worksites and 76% of studies in public settings, with a median absolute increase in stair use of approximately +4% in both settings. An increase in stair use was found in 73% of studies in worksites, with a median absolute change of +4.3%, and in the only study measuring stair use in public settings [START_REF] Nomura | Changing behavioral patterns to promote physical activity with motivational signs[END_REF]. In worksites, all the studies reporting an increase in stair climbing scored weak on quality and were heterogeneous in terms of sample size. The only study of moderate quality found no effect of intervention. In public settings, studies reporting an increase in stair climbing were, for about half of them, of moderate quality and for the other half of weak quality. During follow-up (after the removal of interventions), stair climbing remained elevated compared to baseline in 75% of studies in worksites and 67% of studies in public settings.

Studies using a combination of motivational and directional signs in worksites reported more often an increase in stair climbing compared to studies using motivational signs only (83% vs. 40%). The median absolute change was also markedly higher in the former compared to the latter (+8.1% vs. +0.8%).

Studies measuring stair use found more often a positive change with motivational signs alone compared to studies measuring stair climbing (75% vs. 40%). Most studies, using either motivational signs alone or a combination of motivational and directional signs, received a weak quality rating with a range of sample sizes.

A majority of studies conducting a second intervention phase found an increase in stair climbing compared to the baseline period (67% of studies in worksites and 86% in public settings). The median absolute increase in stair climbing ranged from +2.7% in worksites to +8.7% in public settings. When measuring stair use in worksites, all studies found a positive change, with a median absolute increase of +8.4%. Compared to the first intervention phase, only 36% of studies found an increase in stair use or stair climbing during the second intervention phase. The majority of studies conducting two intervention phases received a weak and moderate quality rating in worksites and public settings, respectively. Finally, three of four studies using stairwell enhancements in addition to POD prompts in worksites [START_REF] Boutelle | Using signs, artwork, and music to promote stair use in a public building[END_REF], Swenson and Siegel, 2013, van Nieuw-Amerongen et al., 2011b) found a significant increase in stair use or stair climbing. The median absolute and relative change in stair climbing was of +4.4% and +39.6%, respectively (Supplementary Table 2).

External validity

The majority of studies lacked reporting on external validity (Table 3). In worksites, 19 of 25 studies reported at least one element of the RE-AIM framework, but only 5 and 2 studies reported 2 and 3 elements, respectively. In public settings, 32, 20 and 4 studies reported one or more, 2 and 3 elements, respectively. Elements receiving the highest attention in both settings were related to the Efficacy dimension: a moderator effect by participant and by setting characteristic(s) was reported in 13 and 9 studies in worksites, and in 32 and 19 studies in public settings, respectively. The criterion reported on the Reach dimension was the participation rate (8 studies in worksites, 5 studies in public settings) which was estimated indirectly when participants could remember the message delivered by the posters, or their thoughts or feelings about the message (Kerr et al., 2001a), or if they reported they had been encouraged to climb stairs by interventions (Eves et al., 2006[START_REF] Kerr | Posters can prompt less active people to use the stairs[END_REF]. Very few studies reported elements on the Implementation dimension. Some studies have included information about the consistent implementation of program and staff expertise (2 studies in worksites, 1 study in public settings), cost of interventions (1 study in both settings) and the time needed to deliver the interventions

(1 study in worksites). Only 1 study in public settings reported elements on Maintenance. No study reported elements on Adoption.

Discussion

The main objective of this systematic review was to provide an updated overview of the effectiveness of We found an increase in stair climbing during the intervention period in about two-thirds of studies in worksites and in three-quarters of studies in public settings. In worksites, the median absolute change observed in our review was larger than that observed in previous studies [START_REF] Eves | Point-of-decision prompts to increase stair use[END_REF]. In addition, the percentage of studies reporting a positive result was higher in our review than in others [START_REF] Nocon | Review Article: Increasing physical activity with point-of-choice prompts--a systematic review[END_REF]. In public settings, the median absolute change and the percentage of studies reporting a positive result observed in our review were similar to results observed in previous reviews [START_REF] Eves | Point-of-decision prompts to increase stair use[END_REF], Nocon et al., 2010). In contrast with previous reviews which found an increase in public settings but not in worksites, our findings appear novel and encouraging.

Studies measuring stair use (ascent and descent combined) in worksites reported a positive result slightly more often than studies measuring specifically stair climbing, with an increase during the intervention period in 73% of studies. The median absolute change, however, was similar. The greater effectiveness obtained when measuring stair use may be explained by a preferential increase in stair descent, as it has been suggested by some studies which found an increase in stair descent but not in stair climbing (Eves, 2012, Kerr, 2001). That discrepancy may be explained by the higher energy cost of stair climbing (the intensity of stair climbing and stair descent is 9.6 and 4.8 metabolic equivalents, respectively) [START_REF] Teh | Heart rate, oxygen uptake, and energy cost of ascending and descending the stairs[END_REF]. Stair climbing being clearly the preferential public health target (Eves et al., 2012b), future studies should more consistently separate stair climbing and stair descent in their analysis.

During the follow-up period, findings were mixed. Stair climbing remained elevated from baseline in three-quarters and two-thirds of studies in worksites and public settings, respectively. It is worth noting that only 35% of the included studies evaluated the short-term effectiveness of interventions (immediately after the removal of the intervention), and only 1 study evaluated their long-term effectiveness (at least six months after their removal). We would therefore recommend, in line with previous reports, that future studies evaluate the maintenance of effects, especially in worksites where it is more likely that the same group of individuals is followed throughout the study (Eves et al., 2012b).

The second objective of the review was to identify what strategy or type of intervention is most likely to be effective. In accordance with our first hypothesis, we observed that studies in worksites using a combination of motivational and directional signs reported more often an increase in stair climbing, and that the median change was larger in these studies. Therefore, the addition of directional signs to motivational signs should be considered in worksites, especially when the stairwell is distant from the elevator and not immediately visible, which is often the case in this setting (Eves and Webb, 2006).

Another intervention strategy, based on stairwell enhancements, was used in 4 studies. Therefore, it was difficult to analyze its effectiveness. However, the first results based on these 4 studies seem promising. The three studies using important stairwell enhancements in addition to POD prompts, such as artwork and music [START_REF] Boutelle | Using signs, artwork, and music to promote stair use in a public building[END_REF], interactive paintings [START_REF] Swenson | Increasing stair use in an office worksite through an interactive environmental intervention[END_REF] or painting and replacement of doors (Van Nieuw-Amerongen et al., 2011a), found high increases in stair use. This finding is in line with the recent results of health promotion programs that combine environmental strategies (e.g. enhancements of physical activity facilities, creation of walking path within worksite) with educational interventions [START_REF] Kahn-Marshall | Making healthy behaviors the easy choice for employees: a review of the literature on environmental and policy changes in worksite health promotion[END_REF].

Regarding our second hypothesis, findings of our review suggest that conducting a second intervention phase allows maintaining over time a higher level of stair climbing compared to baseline, especially in public settings. This is also a promising result since maintaining a long-term change in physical activity behavior represents a major challenge. In worksites, the strategies of interventions used during the first and the second phase in the included studies were diverse. This heterogeneity between studies and between phases of intervention did not allow us analyzing what sequencing of intervention is the most effective in this setting. In contrast, all studies conducted in public settings used motivational prompts during both intervention phases. The possibility to repeat low-cost and easy to implement interventions like posters (Olander and Eves, 2011a) is encouraging from a public health perspective because these interventions could be more easily extended to many public settings.

Elements on external validity were largely underreported in reviewed studies, especially information on implementation, adoption and maintenance. Such findings have been observed in other reviews of health promotion programs that used the RE-AIM framework [START_REF] Dzewaltowski | Behavior change intervention research in community settings: how generalizable are the results?[END_REF][START_REF] Klesges | Review of external validity reporting in childhood obesity prevention research[END_REF][START_REF] Vuillemin | Worksite physical activity interventions and obesity: a review of European studies (the HOPE project)[END_REF]. The lack of external validity information is problematic because it limits the estimation of the potential effectiveness and successful dissemination of the interventions into practice settings [START_REF] Klesges | Review of external validity reporting in childhood obesity prevention research[END_REF]. It is worth noting that the RE-AIM framework is not fully adapted to stair use interventions due to the difficulty in that setting to measure indicators of the "Reach" and "Maintenance" dimensions, such as participation or attrition rate. However, when using the RE-AIM framework it is possible to restrict the analysis to the relevant dimensions available to researchers (www.re-aim.org). Future studies should systematically assess external validity with a focus on the "Effectiveness", "Adoption" and "Implementation" dimensions that fit with stair use interventions.

Study limitations

Our review did not include a meta-analysis given the heterogeneity of studies in terms of design and interventions. Therefore, our quantitative analysis does not provide statistical significance of results; rather, it helps to illustrate the effectiveness of different interventions and to compare it to previous reviews. Beyond that quantitative analysis, we used a harvest plot method proposed recently to synthetize evidence about the effects of heterogeneous and population-level interventions [START_REF] Ogilvie | The harvest plot: a method for synthesising evidence about the differential effects of interventions[END_REF]. This method is useful because it integrates into one graphic several characteristics commonly used to assess level of evidence (study quality, sample size and effectiveness of interventions) (Barnett, 2012). We considered the harvest plot approach more relevant for evaluating stair-use interventions than a general rating system, which would have underestimate the evidence largely because of study design (non-controlled and non-randomized at individual level).

A key limitation of published studies is that they were not controlled or randomized at individual level given the inability of available measurement tools to measure stair use on an individual level. To this end, a new assessment tool could be used [START_REF] Engbers | Measuring stair use in two office buildings: a comparison between an objective and a self-reported method[END_REF]. Each subject is given a chip card with a unique identifier and a detection device, placed behind the doors of the stairwell and elevator, detects the card and records some data (e.g. the direction, the number of floors taken, and the time of stair use).

However, one disadvantage of this technology is its high cost making it difficult to use on a broad scale.

Another limitation of published studies is that they did not assess the number of floors taken. This measure would be of great interest as it would help estimate the clinical significance of the increases in stair climbing observed during the interventions. Indeed, we cannot compare the +4% median change observed in our review with climbing 20 to 40 floors shown to provide health benefits [START_REF] Boreham | Training effects of short bouts of stair climbing on cardiorespiratory fitness, blood lipids, and homocysteine in sedentary young women[END_REF][START_REF] Meyer | Stairs instead of elevators at workplace: cardioprotective effects of a pragmatic intervention[END_REF]. Better estimating the impact of stair interventions at the individual level remains a major challenge.

Conclusion

In conclusion, results of this review emphasize the importance of separating studies by intervention setting (i.e. worksites and public settings) in assessing the effectiveness of stair interventions. The data provide evidence that stair climbing is increased during the interventions in public settings. However, evidence of such effect is limited in worksites. They also suggest that some interventions may be recommended in each setting for greater effectiveness: in worksites, stair climbing is increased to a larger extent when directional signs supplement motivational signs; in public settings, increase in stair use appears maintained over time when interventions include two phases. Designing more effective interventions in worksites appears especially important from a public health perspective because worksites offer more opportunities to climb the stairs throughout the day than public settings and could allow a large number of people reaching the recommended level of physical activity by accumulating short bouts of physical activity. Stairwell enhancements seem promising in addition to POD prompts in this setting, and should be examined in future studies to better assess the evidence of their effectiveness. Information on external validity also needs to be better reported in future studies to help translate research results to practice. --POD = point-of-decision prompts, POD motiv. prompts = POD motivational prompts, POD motiv. and direct. prompts = POD motivational and directional prompts.

1-For studies measuring both stair climbing and stair descent, we have reported only the outcome of stair climbing. 2-Number of people who used the stairs and the elevator or escalator during the study. 3-The number in brackets indicates the of locations in which the intervention was conducted. 4-The study by [START_REF] Howie | Step It UP: a multicomponent intervention to increase stair use in a university residence building[END_REF], conducted in an university dormitory, was coded under worksites because the alternative to stairs was an elevator. Conversely, the study by [START_REF] Andersen | Prompting health professionals to be activity role models--motivating stair use at the 2001 ACSM scientific meeting[END_REF], realized in a convention center, was coded under public settings because the alternative to stairs was an escalator rather than an elevator. As no study reported a decrease in stair use, we did not represent the hypothesis of decrease in stair use.

The height of the bar indicates the study quality (short = weak quality, medium = moderate quality, tall = strong quality). The color of the bar indicates the sample size (white: < 10,000; grey: 10,000 to ≤ 20,000; black: > 20,000). Numbers above the bras refer to study citations.

The median increase in stair use is calculated from all studies (i.e. which found an increase in stair use, or no change or mixed results). Mixed results As no study reported a decrease in stair use or mixed results, we did not represent those hypotheses in the figure.

Figure 2 -Evidence for changes in stair climbing and stair use during and after interventions in worksites

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Median increase in stair use

The bar with the asterisk represents the only study measuring stair use [START_REF] Nomura | Changing behavioral patterns to promote physical activity with motivational signs[END_REF].

The height of the bar indicates the study quality (short = weak quality, medium = moderate quality, tall = strong quality). The color of the bar indicates the sample size (white: < 10,000; grey: 10,000 to ≤ 20,000; black: > 20,000). Numbers above the bras refer to study citations.

The median increase in stair use is calculated from all studies (i.e. which found an increase or no change in stair use). For question 3, 6 relevant confounders were defined for studies conducted in public settings: gender, age, ethnicity, weight status, presence of bags and pedestrian traffic volume. For studies conducted in worksites, 4 confounders were added: time of day (when continuous measures or at different times of day, i.e. morning and afternoon, were realized), height of the building, number of lifts and distance between the entrance to the elevator and the stairs (when more than one building were available for the analyses).

  hypothesis of no change in stair use during or after interventions with two alternative hypotheses of a positive change and mixed results. Each plot consisted of three columns representing the three competing hypotheses. The rows represented our research questions. Each study was represented by a bar in one of the two columns depending on the study result. The height of the bars illustrated the study quality and the shading of the bars indicated the sample size. The harvest plots were combined with the quantitative synthesis: the absolute and relative median change in stair climbing was presented in the fourth column of the plots.

Figure 2 (

 2 Figure 2 (in worksites) and Figure 3 (in public settings) show the harvest plots of evidence for changes in stair climbing and stair use during and after interventions and the calculated mean change in stair use. During the intervention period of all studies, an increase in stair climbing was found in 64% of

  stair-use interventions to increase stair use or stair climbing in worksites and in public settings. The review identified 50 articles including 60 studies analyzing, with different intervention designs, the impact of stair-use interventions. Compared to the previous reviews on this topic by Soler et al. (2010) and Nocon et al. (2010), we have added in the present review 40 and 26 new articles, respectively.

Figure 1 -

 1 Figure 1-Chart flow of the literature search

Figure 2a -

 2a Figure 2a -Evidence for changes of stair climbing in worksites

Figure 3 -

 3 Figure 3 -Evidence for changes of stair climbing and stair use in public settings

Table 1 -Characteristics of the 50 articles included in the review (corresponding to 60 studies) (cont'd)

 1

	Authors	Country	Setting	Alternative to stairs	Assessment tools	Main outcome	Total counts	Duration of interventions (weeks)	Description of intervention (phase 1)	Description of intervention (phase 2)
	(Ryan et al., 2011)	UK	Public setting: train stations (2)	Escalators	Observers	Stair climbing	20,315	4	POD motiv. prompts (posters)	-
	(Webb and Eves, 2005)	UK	Public setting: shopping mall (1)	Escalators	Observers	Stair climbing	32,597	4	POD motiv. prompts (stair-riser banners)	POD motiv. prompts (stair-riser banners)
	(Webb and Eves, 2007a)	UK	Public setting: shopping mall (1)	Escalators	Observers	Stair climbing	81,948	6	Stairwell enhancements	POD motiv. prompts (stair-riser banners)
	(Webb and Eves, 2007b)	UK	Public setting: shopping mall (1)	Escalators	Observers	Stair climbing	77,266	13	POD motiv. prompts (stair-riser banners)
	(Webb and Cheng, 2010)	UK	Public setting: shopping mall (1)	Escalators	Observers	Stair climbing	20,807	5	POD motiv. prompts (stair-riser banners)

Table 2 -Summary of results on quality assessment

 2

					Data collection
		Study design	Confounders	Blinding	methods	Global rating
		n (%)	n (%)	n (%)	n (%)	n (%)
	Studies conducted in worksites (n = 25)
	Strong quality	0 (0%)	0 (0%)	0 (0%)	7 (28%)	0 (0%)
	Moderate quality	15 (60%)	4 (16%)	6 (24%)	15 (60%)	3 (12%)
	Weak quality	10 (40%)	21 (84%)	19 (76%)	3 (12%)	22 (88%)
	Studies conducted in public settings (n = 35)
	Strong quality	0 (0%)	11 (31%)	0 (0%)	12 (34%)	0 (0%)
	Moderate quality	26 (74%)	14 (40%)	0 (0%)	23 (66%)	19 (54%)
	Weak quality	9 (26%)	10 (29%)	35 (100%)	0 (0%)	16 (46%)

 [START_REF] Kwak | A poster-based intervention to promote stair use in blue-and white-collar worksites[END_REF](study arm 2) Lee et al., 2012 (study 2) Lee et al., 2012 (study 3) Russel et al., 1999Swenson and Siegel, 2013 Vanden Auweele et al., 2005 Outcome = stair climbing Coleman and Gonzalez, 2001 (study arm 1) Coleman and Gonzalez, 2001 (study arm 2) Eves et al., 2006 Eves et al., 2012b (study 1) Eves et al., 2012b (study 2) Eves et al., 2012a Ford and Torok, 2008 Howie and Young, 2011 Kerr et al., 2001a (study arm 1) Kerr et al., 2001a (study arm 2) Lee et al., 2012 (study 1) Lewis and Eves, 2012a Marshall et al., 2002 Olander and Eves, 2011a Pillay et al., 2009 van Nieuw-Amerongen et al., 2011 Studies conducted in public settings Outcome = stair use Nomura et al., 2009 Outcome = stair climbing Andersen et al., 1998 Andersen et al., 2006 Andersen et al., 2008 Blamey et al., 1995 Boen et al., 2010 (study 1) Boen et al., 2010 (study 2) Brownell et al., 1980 (study 1) Brownell et al., 1980 (study 2) Coleman and Gonzalez, 2001 (study arm 3) Coleman and Gonzalez, 2001 (study arm 4) Eves et al., 2008a Eves et al., 2008b Eves et al., 2009 (study arm 1) Eves et al., 2009 (study arm 2) Eves et al., 2009 (study arm 3) Iversen et al., 2007 (study arm 1) Iversen et al., 2007 (study arm 2) Kerr et al., 2000 Kerr et al., 2001b (study 1) Kerr et al., 2001b (study 2) Kerr et al., 2001c Kerr et al., 2001d Kerr et al., 2001e (study 1) Kerr et al., 2001e (study 2) Kerr et al., 2001e (study 3) Kerr et al., 2001e (study 4) Lewis and Eves, 2011 Lewis and Eves, 2012b (study arm 1) Lewis and Eves, 2012b (study arm 2) Lewis and Eves, 2012c Muller-Riemenschneider et al., 2010 Olander et al., 2008 Puig-Ribera and Eves, 2010 Russel and Hutchinson, 2000 Ryan et al., 2011 (study arm 1) Ryan et al., 2011 (study arm 2) Webb and Eves, 2005 Webb and Eves, 2007a

Conflicts of interest

The authors declare that there are no conflicts of interest.

Duration of intervention (weeks)

Description of intervention (phase 1) Description of intervention (phase 2) [START_REF] Adams | A systematic approach to the development and evaluation of an intervention promoting stair use[END_REF]) [START_REF] Boutelle | Using signs, artwork, and music to promote stair use in a public building[END_REF]) [START_REF] Bungum | The effects of signage and the physical environment on stair usage[END_REF]) [START_REF] Coleman | Promoting stair use in a US-Mexico border community[END_REF]) [START_REF] Cooley | Increasing stair usage in a professional workplace: a test of the efficacy of positive and negative message prompts to change pedestrian choices[END_REF]) (Eves et al., 2006) (Eves et al., 2012a) (Eves et al., 2012b) [START_REF] Ford | Motivational signage increases physical activity on a college campus[END_REF]) [START_REF] Grimstvedt | Using signage to promote stair use on a university campus in hidden and visible stairwells[END_REF] (Howie and Young, 2011) (Kerr et al., 2001a) [START_REF] Kwak | A poster-based intervention to promote stair use in blue-and white-collar worksites[END_REF] (

1-The total number of included studies was 60. 2-The number of included studies was 25. 3-The number of included studies was 35. OR = Odds ratio, CI = confidence interval, MP = motivational prompts, MDP = motivational and directional prompts, SE = stairwell enhancement, Se = Social environment, / = not measured, NA = not available, ns = non significant, (+) = increase in stair use or stair climbing from baseline (p<0.05), (++) = increase in stair use or stair climbing from baseline and from phase 1 (p<0.05), (-) decrease in stair use or stair climbing from baseline (p<0.05).

Supplementary


Prof Jean-Michel Oppert
email: jean-michel.oppert@aphp.fr

Alice Bellicha

Celina Roda

Jean-Luc Bouillot

Adriana Torcivia

Karine Clement

Christine Poitou

Cecile Ciangura

TITLE: Resistance Training and Protein Supplementation Increase Strength After Bariatric Surgery: a Randomized Controlled Trial

Keywords: clinical trials, bariatric surgery, exercise intervention, protein, physical fitness

STUDY IMPORTANCE QUESTIONS

What is already known about this subject?

• Beneficial effects of bariatric surgery include marked weight loss as well as decreased morbidity and mortality.

• Surgery-induced weight loss is also associated with decreased protein intake as well as decreased lean body mass and muscle strength.

• Physical activity and dietary regimens to optimize health outcomes including body composition and physical fitness after bariatric surgery are not well known.

What does this study add?

• We found that resistance training with added oral protein intake was associated with a significant increase in muscle strength in women with obesity undergoing Roux-en-Y gastric bypass.

• We found that changes in body weight and body composition were comparable to protein supplementation without exercise or to usual follow-up.

• These data provide new evidence to optimize post-surgery follow-up care with exercise and diet that can overcome the loss in muscle strength in people with obesity after bariatric surgery.

INTRODUCTION

In patients with severe obesity, bariatric surgery results in marked and sustained weight loss, decreased mortality [START_REF] Sjostrom | Effects of bariatric surgery on mortality in Swedish obese subjects[END_REF] and improvement in obesity comorbidities, physical function and healthrelated quality of life [START_REF] Mechanick | Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery[END_REF][START_REF] Mingrone | Optimisation of follow-up after metabolic surgery[END_REF]. To enhance health benefits, lifestyle changes represent a major component of follow-up after bariatric surgery [START_REF] Mechanick | Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery[END_REF][START_REF] Mingrone | Optimisation of follow-up after metabolic surgery[END_REF]. Physical activity is a cornerstone of obesity treatment in general (4), however, in patients undergoing bariatric surgery little is known about the effects of physical activity on health outcomes including body composition and physical fitness [START_REF] Coen | A role for exercise after bariatric surgery?[END_REF]. Randomized controlled trials (RCTs) that have assessed the effects of an exercise training program in the first year post-bariatric surgery are few [START_REF] Castello | Impact of aerobic exercise training on heart rate variability and functional capacity in obese women after gastric bypass surgery[END_REF][START_REF] Coen | Clinical trial demonstrates exercise following bariatric surgery improves insulin sensitivity[END_REF][START_REF] Daniels | Effect of a randomised 12-week resistance training programme on muscular strength, cross-sectional area and muscle quality in women having undergone Roux-en-Y gastric bypass[END_REF][START_REF] Hassannejad | The Effect of Aerobic or Aerobic-Strength Exercise on Body Composition and Functional Capacity in Patients with BMI >/=35 after Bariatric Surgery: a Randomized Control Trial[END_REF]. Findings from a narrative review [START_REF] Coen | A role for exercise after bariatric surgery?[END_REF] suggested improvements in metabolic health and cardiorespiratory fitness after endurance training, although there was no consistent additional effect on surgery-induced loss in fat mass and lean body mass.

Resistance, or strength, training is known to increase lean body mass and muscle strength [START_REF] Deschenes | Performance and physiologic adaptations to resistance training[END_REF].

Muscle strength is an important marker related to functional capacity, cardiovascular disease risk factors and mortality [START_REF] Cooper | Mortality Review Group on behalf of the FALCon and HALCyon study teams. Objectively measured physical capability levels and mortality: systematic review and meta-analysis[END_REF][START_REF]Physical Activity Guidelines Advisory Comittee Report[END_REF][START_REF] Lawman | Associations of Relative Handgrip Strength and Cardiovascular Disease Biomarkers in U.S. Adults, 2011-2012[END_REF]. Patients undergoing bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), experience a substantial decrease in lean body mass [START_REF] Ciangura | Dynamics of change in total and regional body composition after gastric bypass in obese patients[END_REF][START_REF] Chaston | Changes in fat-free mass during significant weight loss: a systematic review[END_REF]. Bariatric surgery is also associated with a decrease in absolute muscle strength [START_REF] Herring | Changes in physical activity behaviour and physical function after bariatric surgery: a systematic review and meta-analysis[END_REF]. However, when expressed relative to muscle mass, muscle strength was found unchanged, suggesting that the loss of absolute strength might be due to the decrease in muscle mass [START_REF] Daniels | Effect of a randomised 12-week resistance training programme on muscular strength, cross-sectional area and muscle quality in women having undergone Roux-en-Y gastric bypass[END_REF]. The effect of resistance training, performed alone or in combination with endurance training, on changes in lean body mass and muscle strength during the first year after bariatric surgery has been assessed in only two RCTs [START_REF] Daniels | Effect of a randomised 12-week resistance training programme on muscular strength, cross-sectional area and muscle quality in women having undergone Roux-en-Y gastric bypass[END_REF][START_REF] Hassannejad | The Effect of Aerobic or Aerobic-Strength Exercise on Body Composition and Functional Capacity in Patients with BMI >/=35 after Bariatric Surgery: a Randomized Control Trial[END_REF]. Muscle strength was found improved in both studies [START_REF] Daniels | Effect of a randomised 12-week resistance training programme on muscular strength, cross-sectional area and muscle quality in women having undergone Roux-en-Y gastric bypass[END_REF][START_REF] Hassannejad | The Effect of Aerobic or Aerobic-Strength Exercise on Body Composition and Functional Capacity in Patients with BMI >/=35 after Bariatric Surgery: a Randomized Control Trial[END_REF], whereas lean body mass was found preserved in one study [START_REF] Hassannejad | The Effect of Aerobic or Aerobic-Strength Exercise on Body Composition and Functional Capacity in Patients with BMI >/=35 after Bariatric Surgery: a Randomized Control Trial[END_REF] and unchanged in the other [START_REF] Daniels | Effect of a randomised 12-week resistance training programme on muscular strength, cross-sectional area and muscle quality in women having undergone Roux-en-Y gastric bypass[END_REF].

Therefore, additional RCTs appear needed to further investigate the effectiveness and feasibility of resistance training in the bariatric surgery setting.

Strategies to preserve lean body mass during dietary-induced weight loss in patients with obesity include a combination of resistance training and a sufficient intake of high-quality protein [START_REF] Verreijen | A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial[END_REF]. In the first months after bariatric surgery, energy and protein intake are dramatically reduced [START_REF] Mingrone | Optimisation of follow-up after metabolic surgery[END_REF][START_REF] Verger | Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding[END_REF]. Emerging evidence suggests that whey protein would help increase protein synthesis during energy deficit in patients with overweight or obesity [START_REF] Hector | Whey protein supplementation preserves postprandial myofibrillar protein synthesis during short-term energy restriction in overweight and obese adults[END_REF]. Whey protein, representing 20% of milk proteins, are rapidly digested with an early rise in blood amino acids and increased stimulation of muscle protein synthesis [START_REF] Miller | Effects of whey protein and resistance exercise on body composition: a meta-analysis of randomized controlled trials[END_REF]. The effect of additional protein intake in combination with exercise training after bariatric surgery is however not known.

The aim of this study was to determine whether resistance training with whey protein supplementation is effective in maintaining lean body mass and muscle strength six months after RYGB.

METHODS

Study design

We undertook this single center, open-label, parallel group, RCT between May 1, 2010 and December 31, 2014 at the Department of Nutrition of Pitié-Salpêtrière university hospital (Assistance Publique-Hopitaux de Paris), Paris, France. Patients were followed-up for six months after surgery and underwent the same assessments at visits before and after surgery. The study was approved by the Ethics Committee of Pitié-Salpêtrière hospital (Paris, France).

Participants

Bariatric surgery (RYGB) was offered to patients following current guidelines [START_REF] Fried | Inter-disciplinary European guidelines on surgery of severe obesity[END_REF][START_REF] Institute | Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement[END_REF]. All patients signed an informed written consent to join the study prior to surgery.

Randomization

We randomized patients at the time of surgery to receive usual care with regular medical and nutritional follow-up (control group, CON), or usual care and additional oral protein intake (protein group, PRO), or usual care, additional protein intake and supervised resistance training (protein plus exercise group, PRO+EX).

Procedures

The same RYGB surgical procedure was performed laparoscopically with an alimentary limb of 1.2 to 1.5 m in length [START_REF] Ciangura | Dynamics of change in total and regional body composition after gastric bypass in obese patients[END_REF]. All patients underwent detailed assessments before, and 1, 3, and 6 months after surgery. At each visit, body weight and composition, dietary intake, and various blood parameters were assessed. Health-related quality of life was documented before, and 3, 6 months after surgery. Data on muscle strength, cardiorespiratory fitness, physical activity, and obesity comorbidities were collected before, and 6-months after surgery.

Usual care

General dietary and physical activity counseling was provided to all participants during planned pre-and post-surgery visits at 1, 3 and 6 months, as part of usual care [START_REF] Fried | Inter-disciplinary European guidelines on surgery of severe obesity[END_REF]. Dietary advice aimed to progressively increase protein intake to reach a minimum amount of 60 g/d [START_REF] Mechanick | Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery[END_REF][START_REF] Mingrone | Optimisation of follow-up after metabolic surgery[END_REF]. Patients were encouraged to perform at least 150 minutes/week of moderate-to-vigorous endurance-type physical activity, such as brisk walking [START_REF]Physical Activity Guidelines Advisory Comittee Report[END_REF]. All patients received the same initial prescription to prevent vitamin and mineral deficiencies [START_REF] Fried | Inter-disciplinary European guidelines on surgery of severe obesity[END_REF], starting 15 days before surgery and including iron (2×80 mg/d), calcium (1,000 mg/d), vitamin D (800 IU/d) and a multivitamin and mineral supplement. No other supplement was allowed throughout the study.

Whey protein supplementation

From the first week post-surgery, patients randomized to the PRO and PRO+EX groups were prescribed a daily protein supplementation in the form of a whey-protein enriched powder (Xtreme, INKO, Peyruis, France) delivered in 750 g cans to the participant home by the supplier.

Participants were instructed to consume every day two powder drinks, one in the morning, the other in the afternoon or evening, and shortly after the end of the exercise session for the PRO+EX group, for a total supplemental whey protein dose of 48 g/d (corresponding to 2 measuring spoons to mix 30 g of powder containing 24 g of whey protein with 150 ml of water).

Each protein drink provided approximately 464 kJ of energy, 0.9 g of sucrose, 1 g of fat and 0.3 g of fiber. Patients were asked to return empty cans of protein powder at follow-up visits to assess compliance.

Resistance training program

From week six post-surgery, participants randomized to the PRO+EX group exercised for 1 hour, three times per week on non-consecutive days, during 18 weeks, at our center, under supervision by qualified trainers. Each session included ten minutes of light endurance warming-up, 45 minutes of strength training and five minutes of stretching and cooling-down.

The program was adapted from previous studies [START_REF] Dunstan | Community center-based resistance training for the maintenance of glycemic control in adults with type 2 diabetes[END_REF][START_REF] Colberg | Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association[END_REF]

Anthropometry and body composition

Body composition was measured by whole-body fan-beam Dual Energy X-ray Absorptiometry (DXA) scan (Hologic Discovery W, Hologic, Bedford, MA) [START_REF] Ciangura | Dynamics of change in total and regional body composition after gastric bypass in obese patients[END_REF]. Lean body mass was calculated as weight minus bone mineral content minus fat mass. Body regions (upper limb, lower limb, trunk, and head) were delineated with the use of specific anatomical landmarks. For all patients, right-side half-body scans were carried out from which whole-body composition was extrapolated, as described [START_REF] Rothney | Body composition measured by dual-energy X-ray absorptiometry half-body scans in obese adults[END_REF].

Muscle strength

Isometric maximal grip strength was measured using a handgrip dynamometer (Jamar, Sammons Preston Rolyan, Bolingbrook, Canada) [START_REF] Roberts | A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach[END_REF]. The highest value of 5 maximal trials with each hand was kept for analyses [START_REF] Roberts | A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach[END_REF]. Dynamic maximal strength of lower and upper limbs was measured on strength training equipment (leg press, chest press) [START_REF] Daly | The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized controlled trial[END_REF]. After a warm-up set of ten repetitions with a light weight, subjects were asked to complete sets of three repetitions with the greatest strength and speed. Testing began at 50% of their estimated maximal strength and the load was gradually increased for subsequent sets until failure was reached. The Myotest accelerometer device (Myotest, Acceltec, Sion, Switzerland), is a valid and reliable tool specifically designed for field-based evaluation of muscle strength, velocity and power [START_REF] Comstock | Validity of the Myotest(R) in measuring force and power production in the squat and bench press[END_REF][START_REF] Caruso | Front squat data reproducibility collected with a triple-axis accelerometer[END_REF].

During strength testing, the Myotest was laid flat on the weights that moved on the vertical plane. The Myotest measured the maximum velocity (cm/s), which we used to establish the load-velocity relationship. Given the linear relationship between load and velocity, the maximal load, i.e. load at zero velocity, can be estimated accurately using the load-velocity relationship [START_REF] Jidovtseff | Using the load-velocity relationship for 1RM prediction[END_REF]. The 1-RM, which is a measure of dynamic strength, is then estimated using the following equation: 1-RM = (0.871 x load at zero velocity) -0.624 [START_REF] Jidovtseff | Using the load-velocity relationship for 1RM prediction[END_REF]. For analysis, strength was expressed as absolute values (kg), values relative to body weight and lean body mass and values adjusted for lean body mass.

Cardiorespiratory fitness and physical activity

VO2peak was measured by indirect calorimetry during a graded maximal exercise test on a cycle ergometer [START_REF] Dao | Effects of a multidisciplinary weight loss intervention on anaerobic and aerobic aptitudes in severely obese adolescents[END_REF]. The test protocol started at a workload of 30 W and increased by 30 W every 2 min until volitional exhaustion. VO2peak, determined as the highest attained VO2 during the test, was expressed in absolute values and relative to body mass and to lean body mass. For assessment of habitual physical activity, participants wore the Actigraph GT3X+

(Manufacturing Technology, Pensacola, FL) accelerometer for seven consecutive days during waking hours. Time wear of at least four days and at least eight hours each day defined valid data [START_REF] Unick | Comparison of two objective monitors for assessing physical activity and sedentary behaviors in bariatric surgery patients[END_REF]. The number of counts per minute was calculated from movements on the vertical axis.

Steps were calculated by censoring steps taken at intensity <500 counts/min [START_REF] Tudor-Locke | Accelerometer profiles of physical activity and inactivity in normal weight, overweight, and obese U.S. men and women[END_REF]. Freedson cutpoints were used to quantify sedentary behavior, light, moderate and vigorous intensity physical activity [START_REF] Freedson | Calibration of the Computer Science and Applications, Inc. accelerometer[END_REF].

Other assessments

Health-related quality of life was assessed with the 36-item short-form (SF-36) questionnaire, and was summarized in a physical and a mental component score ranging from 0 (poor) to 100 (good) [START_REF] Leplege | The French SF-36 Health Survey: translation, cultural adaptation and preliminary psychometric evaluation[END_REF]. Food and beverage consumption were assessed by a registered dietician using the dietary history method [START_REF] Oppert | Plasma leptin and acute serotoninergic stimulation of the corticotropic axis in women who are normal weight or obese[END_REF]. Energy (kJ/d) and macronutrient (g/d) intakes were calculated using the national food database. Obesity comorbidities were defined through detailed assessment of each patient medical history and medication use [START_REF] Gesquiere | Medication cost is significantly reduced after Roux-en-Y gastric bypass in obese patients[END_REF]. Blood samples were collected after an overnight fast to measure routine parameters (blood count, blood glucose, protein, prealbumin, albumin, 25(OH)-vitamin-D3, vitamin B12, folate, thiamine).

Outcomes

The primary outcome was pre-to 6-month post-surgery change in lean body mass. Secondary outcomes included changes in upper and lower-limb muscle strength, cardiorespiratory fitness (VO2 peak), objectively-assessed habitual physical activity, dietary protein intake, nutritional status, obesity comorbidities and health-related quality of life.

Statistical analysis

Based on evidence available at the time of the study was designed, it was estimated that subjects lost an average 16 (7.4)% of their lean body mass 6 months after RYGB [START_REF] Ciangura | Dynamics of change in total and regional body composition after gastric bypass in obese patients[END_REF]. Sample sizes were determined a priori and based on detection of preservation effect in lean body mass loss of about one third in subjects with protein supplementation (i.e. averaged loss of 10.7 [4.9]%) [START_REF] Layman | Dietary protein and exercise have additive effects on body composition during weight loss in adult women[END_REF].

We assumed a similar additional effect in subjects with strength training.

RESULTS

Out of 290 subjects assessed for eligibility, 71 patients were non-included because they did not meet inclusion criteria and 125 refused to participate (Supplementary Figure 1). Ninety-four patients were included in the study, 76 were randomized to receive either usual follow-up (CON, n=22), usual follow-up and additional protein intake (PRO, n=31) or usual follow-up, additional protein intake and exercise training (PRO+EX, n=23) and included in the ITT analysis, with 47 of them meeting the definition of completers. In the PRO and PRO+EX groups, we found no difference between non completers (n=29) and completers (n=25) in baseline characteristics, except for protein intake.

Baseline characteristics were similar between groups (Table 1

DISCUSSION

This is a first RCT to test whether resistance training, under supervision for 18 weeks, with protein supplementation in the form of oral intake of whey protein added to the usual diet, was effective in maintaining lean body mass after RYGB. Although body composition changes did not differ across groups, other results show an increase in muscle strength which was found two to three times higher for lower limbs in the group following the exercise training program and the protein supplementation compared to the group with protein supplementation without exercise and to the group that followed the usual post-surgery medical and nutritional care.

Results also show that surgery-induced weight loss in itself was associated with a series of beneficial health effects including increased objectively-measured habitual physical activity and cardiorespiratory fitness, adding to current evidence indicating an overall improved cardiovascular risk profile in patients after bariatric surgery. Post-surgery improvement in cardiorespiratory fitness has been previously reported in several observational studies [START_REF] Seres | Increased exercise capacity after surgically induced weight loss in morbid obesity[END_REF].

Changes in habitual physical activity, however, are still a matter of discussion. According to recent reviews, data generated from self-reported questionnaires consistently indicated an increase in physical activity whereas data from objective measures indicated no change or only modest increases [START_REF] Coen | A role for exercise after bariatric surgery?[END_REF][START_REF] Herring | Changes in physical activity behaviour and physical function after bariatric surgery: a systematic review and meta-analysis[END_REF][START_REF] Jacobi | Physical activity and weight loss following bariatric surgery[END_REF].

A unique of our trial is the design combining muscle strength training and protein supplementation in patients undergoing bariatric surgery. At the time the study was designed and funded, no RCT had been published testing the effects of exercise training, whatever type, on health outcomes after bariatric surgery. We initially focused on changes in lean body mass based on results or our previous observational study describing changes in body composition through serial DXA assessments after RYGB [START_REF] Ciangura | Dynamics of change in total and regional body composition after gastric bypass in obese patients[END_REF]. In that study, in patients closely monitored and following usual care recommendations [START_REF] Fried | Inter-disciplinary European guidelines on surgery of severe obesity[END_REF][START_REF] Institute | Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement[END_REF], lean body mass loss amounted to about a third of body weight loss in the six-month to one-year time period after RYGB [START_REF] Ciangura | Dynamics of change in total and regional body composition after gastric bypass in obese patients[END_REF]. In addition to functional consequences, risk of malnutrition and reduced capacity to cope with aggression, this loss in lean body mass would induce a decrease in energy expenditure possibly contributing to weight regain as observed in many patients at long term after surgery (3). Since then, results of several trials suggested similar changes in lean body mass with exercise training compared to usual care after bariatric surgery [START_REF] Coen | A role for exercise after bariatric surgery?[END_REF], in line with the present data. None of these previous trials however investigated the effects of combining strength training with additional protein intake.

Indeed, sufficient intake of high-quality protein is necessary to preserve or increase lean body mass through strength training [START_REF] Verreijen | A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial[END_REF]. This also explains why we decided not to include an exercise only group in our trial.

A recent review has evidenced decreased muscle strength after bariatric surgery [START_REF] Herring | Changes in physical activity behaviour and physical function after bariatric surgery: a systematic review and meta-analysis[END_REF].

Interestingly, our findings show that gains in muscle strength can be achieved in the first months following bariatric surgery with progressive moderate-intensity strength training. This gain in muscle strength is likely to be a beneficial effect regarding physical functioning given the major contribution of muscle strength in performing daily living physical activity in persons with obesity [START_REF] Baillot | The 6-min Walk Test Reflects Functional Capacity in Primary Care and Obese Patients[END_REF]. In the PRO+EX group, we observed an increase of 12% and 43% on average in lower limb muscle strength in absolute and relative terms, respectively. Such an increase in absolute strength is lower than that usually reported after resistance training in previously untrained women [START_REF] Hakkinen | Changes in agonist-antagonist EMG, muscle CSA, and force during strength training in middle-aged and older people[END_REF] but is comparable to the gain observed after resistance training following bariatric surgery [START_REF] Daniels | Effect of a randomised 12-week resistance training programme on muscular strength, cross-sectional area and muscle quality in women having undergone Roux-en-Y gastric bypass[END_REF]. In a non-randomized trial, Daniels et al. reported an 18 to 36% increase in lower-limb absolute strength after 12-week resistance training. Increases in muscle strength of approximately 20% have also been found after resistance training when performed during dietary-induced weight loss [START_REF] Josse | Increased consumption of dairy foods and protein during diet-and exercise-induced weight loss promotes fat mass loss and lean mass gain in overweight and obese premenopausal women[END_REF]. The decrease in lean body mass associated with weight loss might prevent large gains in absolute strength, and even more so during surgery-induced weight loss. Our findings therefore add to emerging evidence showing that it is feasible to substantially increase muscle strength with physical training, even during marked negative energy balance leading to important lean body mass loss. This increase in muscle strength was not associated with additional improvements in quality of life, in line with previous studies [START_REF] Shah | High-volume exercise program in obese bariatric surgery patients: a randomized, controlled trial[END_REF].

Gains in muscle strength as found here might be attributable to neural adaptations rather than muscle hypertrophy. Neural adaptations occurring during the first months of resistance training mainly include increased motor unit activation of the trained muscles and decreased cocontraction of antagonists [START_REF] Deschenes | Performance and physiologic adaptations to resistance training[END_REF]. Uncoupling between muscle strength and mass after long-term resistance training has been well described [START_REF] Deschenes | Performance and physiologic adaptations to resistance training[END_REF]. For example, a 66% increase in strength after a 6-month strength training program performed in middle-aged women under normo-caloric conditions was explained by a 34% increase in muscle activation and a 9% increase in muscle cross-section [START_REF] Hakkinen | Changes in agonist-antagonist EMG, muscle CSA, and force during strength training in middle-aged and older people[END_REF].

Protein intake appeared sufficient to maintain protein status, although it was found insufficient to observe an effect on lean body mass. In the control group, energy and protein intakes were indeed very low during the first months after surgery, in agreement with previous literature [START_REF] Mingrone | Optimisation of follow-up after metabolic surgery[END_REF].

With the use of a whey protein supplement, subjects in the two intervention groups achieved increased protein intake compared to usual care. Protein intake was on average over 60 g/d 3 months after RYGB, which corresponds to thresholds suggested in recent guidelines for bariatric surgery patients [START_REF] Mechanick | Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery[END_REF][START_REF] Mingrone | Optimisation of follow-up after metabolic surgery[END_REF]. This was however far from recommended protein intake for maintenance of muscle mass during strength training which typically exceed 1 g/kg/d [START_REF] Morton | A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults[END_REF]. The very low protein intake in a context of marked negative energy balance would be a main reason to explain the absence of significant effect on lean body mass, which was our main hypothesis. Whey protein is known to induce higher increases in muscle protein synthesis compared to other proteins [START_REF] Miller | Effects of whey protein and resistance exercise on body composition: a meta-analysis of randomized controlled trials[END_REF]. During previous studies of dietary-induced weight loss, whey protein supplementation led to lean mass retention although the effect size was modest [START_REF] Institute | Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement[END_REF]. The effect of whey protein on muscle metabolism during negative energy balance as seen after bariatric surgery has not been investigated.

Strengths of the present RCT include the supervised and progressive strength training program, the homogeneous sample, the objective assessment of a large set of health outcomes that were found favorably associated with surgery-induced weight loss, the careful follow-up of patients at pre-specified post-surgery time points that were the same for all patients. Some limitations should be noted. Adherence to additional protein intake was self-reported. We included only women and similar investigations should also be performed in men. Mean BMI was higher in non-included subjects, which might limit the generalizability of findings. Our assessment of muscle mass was indirect as it was based on DXA-measured lower limb lean body mass. Since this trial was designed, the number of sleeve gastrectomy procedures has risen sharply (3).

Whether our results also apply to different bariatric procedures would need to be studied

CONCLUSION

This trial shows that significant improved muscle strength was achieved through the combination of resistance training and additional protein intake during six months after RYGB.

Although no difference was found regarding weight and lean body mass loss or improvement in cardiorespiratory fitness after bariatric surgery, these findings add to the body of knowledge indicating the adjunct value of physical exercise training in the follow-up care of bariatric surgery in patients with severe obesity.

Resistance Training and Protein Supplementation Increase Strength After Bariatric Surgery: a Randomized Controlled Trial,

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  BMI) of 40 kg/m 2 or higher, or a BMI of 35 kg/m 2 or higher with at least one obesity comorbidity. Exclusion criteria were diagnosis of recent coronary event, uncontrolled hypertension, proliferative diabetic retinopathy or disabling neuropathy,

	dialysis treatment, orthopedic problems limiting exercise, abnormal cardiac stress test, ongoing
	or planned pregnancy, refusal to participate in a physical activity program, concurrent
	participation in a structured physical activity program, food intolerance to milk protein products.

Inclusion criteria were female gender, age between 18 and 65 years, place of residence in Paris or its region, body mass index (

  -way analysis of variance or Kruskal-Wallis test (for continuous data) and Chi-square test or Fisher's exact test (for categorical data) as appropriate. Linear mixed models were used to estimate and test changes over time. The terms "group", "time" and "group x time" were included as fixed effects. Each follow-up wave was added to the model as a dummy variable. Changes in muscle strength independent of changes in regional lean mass were estimated by including regional lean body mass variable as a covariate in the corresponding models. Primary analyses were intention-to-treat (ITT), involving all randomized patients (n=76). For analyses of lower limb muscle strength data, implausible values (1-RM values over 320 kg) led to exclude data from 3 subjects. All analyses were then repeated on completers

	Setting an overall
	power to 80% with alpha at 0.05 yielded an estimate of 75 patients (with 31 in PRO group, 22 in
	PRO+EX and CON groups).
	Characteristics of interest were summarized with frequencies and percentages for categorical
	data, means and standard deviations (SDs) or medians and 25 th and 75 th percentiles (P25-P75) for

continuous data. Variables that did not meet the assumption of a normal distribution were logtransformed and retested. If the assumption of normality could not be met by transformation, we used non-parametric tests for comparing groups. Baseline preoperative characteristics were analyzed with onedefined as subjects taking ≥24 g/d additional protein intake (i.e. half of total supplemental whey protein dose) and participating in ≥2 exercise sessions/week during 16 weeks (i.e. the lower limit of prescribed exercise frequency). Two-sided P-values are reported. The dose-response relationship across randomized groups was examined by performing a test of trend and examining linear and non linear (quadratic) contrasts. Results were considered significant at P-value<0.05. Statistical analyses were performed with STATA (release 13; Stata Corporation, College Station, TX).

  ). Mean (SD) age was 42.4 (9.9) years, body weight: 116.2 (16.2) kg, BMI: 44.0 (5.8) kg/m², and percent body fat: 50.1 (4.0)%. For lower limb and upper limb strength in ITT analysis, when expressed relative to body weight or to lean body mass, there was a significant group effect and group x time interaction. In completers, group x time interaction was significant for lower limb and upper limb muscle strength expressed in absolute and relative values. In completers, a dose-response relationship was evidenced for changes in lower and upper limb 1-RM between CON, PRO and PRO+EX groups (plinear<0.05).The supplementary table shows details of changes in dietary intakes.Figure1illustrates the relative change in lower limb and upper limb muscle strength in percent change from baseline in completers. In the PRO+EX group after RYGB, increases in muscle strength were 12 and 13% in absolute values and 43% and 44% relative to body weight, for lower and upper limb respectively (Figure1). When muscle strength was expressed relative to lean body mass, increases equaled to 33% and 30%.

	Compared to non-included patients, those included had a lower BMI (BMI in non-included
	patients: 46.6 (6.4) kg/m², p=0.002) and had similar age (43.1 [12.6], p=0.719). The median
	(P25-P75) number of exercise training sessions attended in the PRO+EX group was 35 (15-40).
	The median (P25-P75) whey protein supplementation was 20.8 (12.5-41.7 g/d) in the PRO group Overall, six months after RYGB, VO2peak increased by 2.8 (4.9) mL/kg/min and the number of
	and 36.5 (29.2-41.7) g/d in the PRO+EX group. At baseline, 5 participants reached the physical steps 1178 (3082) steps/d. A significant time effect without difference between groups was
	also observed for changes in handgrip strength, energy and macronutrient intakes, and
	nutritional parameters. Daily protein intake (including the additional protein intake) six months
	after RYGB was 60.2 (17.3), 74.5 (22.4) and 81.4 (27.7) g/d in CON, PRO and PRO+EX

activity threshold of 150 min/week of 10-min bouts moderate-to-vigorous physical activity (1 from the CON group, and 4 from the PRO group).

Table

2

shows changes in anthropometry and body composition, muscle strength, cardiorespiratory fitness, habitual physical activity, quality of life, dietary intake and nutritional status after RYGB according to treatment groups in ITT analysis (Table

2A

) and in completers only (Table

2B

). A significant time effect was observed for almost all variables, both in ITT and completers. Overall, six months after RYGB, lean body mass decreased by 8.2 (3.1) kg in parallel with a decrease in body weight, BMI and fat mass

(27.5 (7.4

) kg and 10.4 (2.6) kg/m², and 19.6 (4.8) kg, respectively), without significant difference between groups. subjects, respectively. No serious adverse effect was recorded.

Table 1 . Baseline Preoperative Characteristics of Patients Undergoing Roux-en-Y Gastric Bypass Surgery

 1 -value from a one-way analysis of variance, b Kruskal-Wallis test, c Chi-square test or d Fisher's exact test. p-value from test performed on log-transformed data for vitamins (except for serum folate).

		All patients		Randomised
		N=76		N=76
			CON	PRO	PRO + EX
			N=22	N=31	N=23
	Age, years	42.4 (9.9)	43.9 (10.7)	42.5 (8.7)	40.9 (10.8)	0.604 a
	Anthropometry and body
	composition
	Body weight, kg (n=76)	116.2 (16.2)	116.3 (19.3)	115.7 (14.9)	116.7 (15.4)	0.972 a
	BMI, kg/m 2 (n=76)	44.0 (5.8)	43.6 (6.2)	43.3 (6.0)	45.2 (5.2)	0.484 a
	Body fat, % (n=75)	50.1 (4.0)	50.2 (3.4)	49.7 (4.8)	50.4 (3.4)	0.794 a
	Fat mass, kg (n=75)
	Total, kg	58.3 (10.9)	58.7 (11.8)	57.4 (10.8)	59.2 (10.5)	0.527 a
	Trunk fat mass, kg	28.1 (5.5)	27.8 (6.2)	27.8 (5.4)	28.8 (5.1)	0.753 a
	LBM, kg (n=75)
	Total, kg	55.5 (6.7)	55.6 (8.4)	55.9 (6.1)	54.8 (5.9)	0.844 a
	Lower limb LBM, kg	19.7 (3.3)	19.6 (3.6)	19.7 (3.3)	19.8 (3.1)	0.990 a
	Upper limb LBM, kg	4.5 (0.9)	4.3 (0.9)	4.5 (1.0)	4.5 (0.7)	0.552 a
	Muscle strength
	Handgrip, kgF (n=76)	32.0 (6.2)	30.6 (5.7)	33.0 (7.0)	32.0 (5.6)	0.388 a
	Lower limb 1-RM
	Absolute, kg (n=71)	179.5 (47.8)	175.7 (53.1)	174.6 (42.0)	189.2 (50.4)	0.519 a
	Relative to body weight, kg/kg (n=71)	1.57 (0.45)	1.58 (0.59)	1.52 (0.39)	1.62 (0.38)	0.734 a
	Relative to lower limb LBM,	9.31 (2.85)	9.41 (3.69)	8.94 (2.54)	9.65 (2.31)	0.682 a
	kg/kgLBM (n=70)
	Upper limb 1-RM
	Absolute, kg (n=75)	32.1 (8.1)	31.4 (6.9)	32.1 (8.2)	32.9 (9.2)	0.836 a
	Relative to body weight, kg/kg (n=75)	0.28 (0.07)	0.27 (0.05)	0.28 (0.08)	0.28 (0.08)	0.834 a
	Relative to upper limb LBM,	7.37 (1.89)	7.56 (2.03)	7.31 (1.97)	7.25 (1.70)	0.842 a
	kg/kgLBM (n=74)
	Cardiorespiratory fitness
	VO2peak
	Absolute, L/min (=73)	2.10 (0.49)	2.21 (0.50)	2.08 (0.46)	2.02 (0.51)	0.433 a
	Relative to body weight, mL/min/kg	18.2 (4.2)	19.2 (4.9)	18.1 (3.5)	17.4 (4.3)	0.373 a
	(=73)
	Relative to LBM, mL/min/kgLBM	38.0 (9.0)	40.1 (10.4)	37.3 (7.5)	36.9 (9.3)	0.421 a
	(=73)
	Habitual physical activity
	Wear-time, min/d (n=70)	786.0 (74.2)	798.2 (67.7)	784.9 (81.6)	775.2 (71.7)	0.607 a
	Counts per minute (n=70)	314.5 (97.8)	295.7 (85.6)	344.7 (116.5)	293.2 (72.4)	0.108 a
	Steps per day (n=70)	6450.2 (2483.5) 6573.6 (2188.7) 6966.5 (2843.7) 5638.5 (2119.0) 0.174 a
	LPA, min/d (n=70)	286.8 (71.4)	282.0 (75.8)	293.8 (76.5)	282.2 (61.8)	0.804 a
	MVPA, min/d (n=70), median (P25-P75) 24.6 (16.7-35.9) 25.7 (14.7-33.8) 25.1 (17.7-41.8) 20.9 (15.9-33.7) 0.338 b
	MVPA in ≥10 min bouts, (n=70),	22 (0-67)	29 (0-66)	22.0 (0-109.5)	20 (10-49)	0.740 b
	min/week, median (P25-P75)
	Accumulate 150 min/week MVPA in	5 (7.1)	1 (4.8)	4 (14.3)	0 (0)	0.177 d
	≥10 min bouts, No. (%)
	Quality of life
	Physical dimension (n=74)	37.7 (6.7)	38.1 (6.5)	37.1 (6.6)	38.1 (7.5)	0.839 a
	Mental dimension (n=74)	43.1 (8.0)	44.2 (8.6)	42.8 (7.4)	42.5 (8.5)	0.759 a
	Comorbidities
	Type 2 diabetes, No. (%) (n=76)	21 (27.6)	5 (22.7)	8 (25.8)	8 (34.8)	0.636 c
	Sleep apnea syndrome, No. (%) (n=76)	39 (51.3)	10 (45.5)	18 (58.1)	11 (47.8)	0.613 c
	Hypertension, No. (%) (n=75)	22 (29.3)	6 (27.3)	10 (33.3)	6 (26.1)	0.821 c

pNumber of observations for each item may vary due to missing data.

Table 2 . Changes in Anthropometry, Body Composition, Muscle Strength, Cardiorespiratory Fitness, Habitual Physical Activity and Quality of Life after Roux-en-Y

 2 RM, one repetition maximum; 95% CI, confidence interval at 95%; BMI, body mass index; CON, control group; PRO, protein intake group; PRO + EX, protein intake and supervised strength training group; LBM, lean body mass; LPA, light physical activity; MVPA, moderate-to-vigorous physical activity P-values for Group, Time, interaction (Group x Time) terms in mixed models Relative to body weight, kg/kg +0.12 (-0.11;0.35) +0.11 (-0.20;0.43) +0.68 (0.37;0.99) 0.071

	Gastric Bypass Surgery
	A. Intention-to-treat (N=76)
		Change from baseline (95% CI)		P-value
		CON	PRO	PRO + EX	Group	Time	Group
							by time
		N=22	N=31	N=23
	Anthropometry and body
	composition
	Body weight, kg	-28.0 (-30.6;-25.4) -27.2 (-29.4;-25.1) -27.4 (-29.9;-24.8) 0.970	<0.001	0.664
	BMI, kg/m 2	-10.5 (-11.4;-9.6)	-10.2 (-11.0;-9.4) -10.6 (-11.5;-9.7)	0.503	<0.001	0.686
	Fat mass, kg	-19.7 (-21.5;-17.9) -19.8 (-21.3;-18.2) -19.4 (-21.1;-17.6) 0.808	<0.001	0.417
	LBM, kg	-8.8 (-10.1;-7.5)	-8.2 (-9.3;-7.1)	-7.7 (-9.0;-6.5)	0.803	<0.001	0.899
	Lower limb LBM, kg	-3.6 (-4.3;-3.0)	-3.0 (-3.6;-2.5)	-3.2 (-3.8;-2.6)	0.712	<0.001	0.557
	Upper limb LBM, kg	-0.3 (-0.6;-0.1)	-0.3 (-0.5;-0.1)	-0.5 (-0.8;-0.3)	0.633	<0.001	0.554
	Muscle strength
	Handgrip, kgF	-21.0 (-43.1;1.1)	-29.1 (-47.5;-10.6) -22.9 (-44.1;-1.4)	0.427	<0.001	0.840
	Lower limb 1-RM
	Absolute, kg	-30.4 (-55.8;-5.0)	-19.6 (-41.5;2.3) +4.68 (-19.6;28.9) 0.012	0.032	0.128
	Relative to body weight, kg/kg +0.12 (-0.14;0.38)	+0.22 (-0.01;0.44) +0.59 (0.34;0.84)	0.033	<0.001	0.021
	Relative to lower limb LBM,	-0.08 (-1.53;1.38)	+0.19 (-1.08;1.46) +2.22 (0.83;3.60)	0.041	0.055	0.043
	kg/kgLBM
	Adjusted for lower limb LBM,	-19.3 (-46.3;7.7)	-9.1 (-32.3;14.2) +14.6 (-10.9;40.2) 0.010	0.584	0.136
	kg
	Upper limb 1-RM
	Absolute, kg	-6.2 (-9.9;-2.6)	-4.8 (-7.9;-1.7)	-0.5 (-4.0;3.0)	0.135	<0.001	0.061
	Relative to body weight, kg/kg +0.02 (-0.02;0.06)	+0.03 (-0.01;0.06) +0.09 (0.05;0.12)	0.175	<0.001	0.050
	Relative to upper limb LBM,	-1.0 (-2.0;-0.1)	-0.8 (-1.6;0.1)	+0.9 (-0.1;1.9)	0.242	0.272	0.010
	kg/kgLBM
	Adjusted for upper limb LBM,	-5.2 (-9.0;-1.5)	-4.1 (-7.3;0.9)	+1.2 (-2.5;4.9)	0.123	0.012	0.029
	kg
	Cardiorespiratory fitness
	VO2peak
	Absolute, L/min	-0.4 (-0.6;-0.2)	-0.3 (-0.4;-0.1)	-0.1 (-0.3;0.1)	0.759	<0.001	0.276
	Relative to body weight,	+1.8 (-0.3;3.9)	+2.5 (0.7;4.3)	+4.0 (1.9;6.1)	0.764	<0.001	0.324
	mL/min/kg
	Relative to LBM,	-1.0 (-5.1;3.1)	+0.4 (-3.1;3.8)	+3.2 (-0.8;7.3)	0.663	0.443	0.335
	mL/min/kgLBM
	Habitual physical activity
	Wear-time, min/d	-7.5 (-45.7;30.6)	-3.0 (-36.4;30.4)	-8.3 (-46.5;29.8)	0.551	0.561	0.975
	Counts per minute	+49.4 (-0.1;98.9)	+10.7 (-32.9;54.4) +31.0 (-18.5;80.5) 0.337	0.031	0.515
	Steps per day	+1716 (358;3074)	+629 (-560;1819) +1022 (-336;2379) 0.164	0.004	0.496
	LPA, min/d	+3.1 (-26.5;32.6)	-23.7 (-49.7;2.3)	+1.5 (-28.1;31.0)	0.995	0.445	0.311
	MVPA, min/d	+9.6 (1.9;17.3)	+5.7 (-1.1;12.5)	+5.7 (-2.0;13.5)	0.178	0.001	0.717
	MVPA in ≥10 min bouts,	+30.5 (1.2:59.9)	+20.3 (-5.7;46.4) +14.8 (-14.6;44.1) 0.114	0.009	0.751
	min/week
	Quality of life
	Physical dimension	+8.7 (6.1;11.2)	+9.4 (7.2;11.6)	+10.0 (7.4;12.7)	0.994	<0.001	0.438
	Mental dimension	+5.8 (2.3;9.3)	+8.2 (5.3;11.2)	+8.9 (5.3;12.4)	0.929	<0.001	0.800
	Dietary intake
	Energy intake, kJ/d	-2196.2 (-2920.7;-	-2737.2 (-3362.6;-	-1961.9 (-2715.4;-	0.492	<0.001	0.526
		1471.7)	2111.8)	1208.5)

ACKNOWLEDGMENTS

Individual participant data or any other data will not be available.

This research was supported by grant AOR 09059 from the Programme Hospitalier de Recherche Clinique (PHRC, France).

DISCLOSURE:

The authors declared no conflict of interest.

ABSTRACT

Objective: Physical activity and dietary regimens to optimize health outcomes after bariatric surgery are not well known. We aimed to determine whether resistance training with dietary protein supplementation is effective in maintaining body composition and physical fitness after obesity surgery.

Method: Seventy-six women with obesity undergoing Roux-en-Y gastric bypass were randomly assigned at the time of surgery to receive either usual care (controls or CON, n=22), usual care and additional (whey) protein intake (PRO, n=31), or usual care, additional protein intake and supervised strength training for 18 weeks (PRO+EX, n=23). The primary outcome was pre-to six-month post-surgery change in lean body mass (by dual-energy X-ray absorptiometry).

Secondary outcomes included changes in muscle strength (by 1-RM testing).

Results