Can Pharmacological Conditioning as an Add-On Treatment Optimize Standard Pharmacological Treatment in Patients with Recent-Onset Rheumatoid Arthritis? A Proof-of-Principle Randomized Clinical Trial.

Medication regimens using conditioning via variable reinforcement have shown similar or improved therapeutic effects as full pharmacological treatment, but evidence in patient populations is scarce. This proof-of-principle double-blind randomized clinical trial examined whether treatment effects in recent-onset rheumatoid arthritis (RA) can be optimized through pharmacological conditioning. After four months of standardized treatment (n = 46), patients in clinical remission (n = 19) were randomized to the Control group (C), continuing standardized treatment (n = 8), or the Pharmacological Conditioning (PC) group, receiving variable treatment according to conditioning principles (n = 11). After eight months, treatment was tapered and discontinued linearly (C) or variably (PC). Standard treatment led to large improvements in disease activity and HRQoL in both groups. The groups did not differ in the percentage of drug-free clinical remission obtained after conditioning or continued standard treatment. The PC group did show a larger decrease in self-reported disease activity (Cohen's d = 0.9) and a smaller increase in TNF-α levels (Cohen's d = 0.7) than the C group. During all phases, more differences between groups were found for the patients who followed protocol than for the intention-to-treat sample. Although the results are not conclusive, pharmacological conditioning may have some advantages in terms of disease progression and stability, especially during the conditioning phase, compared with standard clinical treatment. The effects may be particularly beneficial for patients who show a good initial response to increased medication dosages.

Effectiveness of Human-Supported and Self-Help eHealth Lifestyle Interventions for Patients With Cardiometabolic Risk Factors: A Meta-Analysis.

OBJECTIVE: eHealth is a useful tool to deliver lifestyle interventions for patients with cardiometabolic diseases. However, there are inconsistent findings about whether these eHealth interventions should be supported by a human professional, or whether self-help interventions are equally effective. METHODS: Databases were searched between January 1995 and October 2021 for randomized controlled trials on cardiometabolic diseases (cardiovascular disease, chronic kidney disease, type 1 and 2 diabetes mellitus) and eHealth lifestyle interventions. A multilevel meta-analysis was used to pool clinical and behavioral health outcomes. Moderator analyses assessed the effect of intervention type (self-help versus human-supported), dose of human support (minor versus major part of intervention), and delivery mode of human support (remote versus blended). One hundred seven articles fulfilled eligibility criteria and 102 unique ( N = 20,781) studies were included. RESULTS: The analysis showed a positive effect of eHealth lifestyle interventions on clinical and behavioral health outcomes ( p < .001). However, these effects were not moderated by intervention type ( p = .169), dose ( p = .698), or delivery mode of human support ( p = .557). CONCLUSIONS: This shows that self-help eHealth interventions are equally effective as human-supported ones in improving health outcomes among patients with cardiometabolic disease. Future studies could investigate whether higher-quality eHealth interventions compensate for a lack of human support.Meta-analysis registration: PROSPERO CRD42021269263 .

Susceptibility to Nocebo Hyperalgesia, Dispositional Optimism, and Trait Anxiety as Predictors of Nocebo Hyperalgesia Reduction.

OBJECTIVES: The current paper explores the psychological predictors of nocebo hyperalgesia and whether the reduction of nocebo hyperalgesia can be predicted by susceptibility to nocebo hyperalgesia and psychological characteristics. METHODS: Nocebo effects on pressure pain were first experimentally induced in 83 healthy female participants through conditioning with open-label instructions about the pain-worsening function of a sham TENS device to assess susceptibility to nocebo hyperalgesia. Participants were then randomized to 1 out of 2 nocebo-reduction conditions (counterconditioning/extinction) or to continued nocebo-conditioning (control), each combined with open-label instructions about the new sham device function. Dispositional optimism, trait and state anxiety, pain catastrophizing, fear of pain, and body vigilance were assessed at baseline. RESULTS: The results showed that lower optimism and higher trait anxiety were related to a stronger induction of nocebo hyperalgesia. Moreover, a stronger induction of nocebo hyperalgesia and higher trait anxiety predicted a larger nocebo reduction across interventions. Also, nocebo hyperalgesia and optimism moderated the effects of the nocebo-reduction interventions, whereby larger nocebo hyperalgesia and lower optimism were associated with a larger nocebo reduction after counterconditioning, compared with control, and also extinction for larger nocebo hyperalgesia. DISCUSSION: Our findings suggest that open-label conditioning leads to stronger nocebo hyperalgesia when trait anxiety is high and dispositional optimism is low, while these psychological characteristics, along with larger nocebo hyperalgesia, also predict open-label counterconditioning to be an effective nocebo-reduction strategy. Susceptibility to nocebo hyperalgesia, trait anxiety, and dispositional optimism might be indicators of a flexible pain regulatory system.

eHealth to Improve Psychological Functioning and Self-Management of People With Chronic Kidney Disease: A Randomized Controlled Trial.

OBJECTIVE: Psychological distress is common among patients with chronic kidney disease and can interfere with disease self-management. We assessed the effectiveness of the personalized E-GOAL electronic health care pathway with screening and cognitive-behavioral therapy including self-management support, aimed to treat psychological distress and facilitate self-management among people with chronic kidney disease not on dialysis ( N = 121). METHODS: Primary outcome of the open two-arm parallel randomized controlled trial in four Dutch hospitals was psychological distress at posttest directly after the intervention and at 3-month follow-up. Secondary outcomes were physical and mental health-related quality of life, self-efficacy, chronic disease self-management, and personalized outcomes, that is, perceived progress compared with the previous time point on functioning (e.g., mood or social functioning) and self-management (e.g., dietary or medication adherence) outcomes that were prioritized by each individual. RESULTS: Linear mixed-effects analyses showed no significant time-by-group interaction effects for psychological distress, health-related quality of life, self-efficacy, and chronic condition self-management, whereas analyses of covariance showed significantly more perceived progress in the intervention group at posttest on personally prioritized areas of functioning ( b = 0.46, 95% confidence interval = 0.07-0.85) and self-management ( b = 0.55, 95% confidence interval = 0.16-0.95), with Cohen d values of 0.46 and 0.54 (medium effects), respectively. Effects on personalized outcomes were maintained at follow-up. CONCLUSIONS: Compared with regular care only, the electronic health intervention did not reduce psychological distress, whereas personalized outcomes did improve significantly after intervention. Future studies could consider personalized outcomes that reflect individually relevant areas and treatment goals, matching person-tailored treatments. TRIAL REGISTRATION: Registered at the Netherlands Trial Register with study number NTR7555 ( https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7555 ).

The Bradley-Terry Regression Trunk approach for Modeling Preference Data with Small Trees.

This paper introduces the Bradley-Terry regression trunk model, a novel probabilistic approach for the analysis of preference data expressed through paired comparison rankings. In some cases, it may be reasonable to assume that the preferences expressed by individuals depend on their characteristics. Within the framework of tree-based partitioning, we specify a tree-based model estimating the joint effects of subject-specific covariates over and above their main effects. We, therefore, combine a tree-based model and the log-linear Bradley-Terry model using the outcome of the comparisons as response variable. The proposed model provides a solution to discover interaction effects when no a-priori hypotheses are available. It produces a small tree, called trunk, that represents a fair compromise between a simple interpretation of the interaction effects and an easy to read partition of judges based on their characteristics and the preferences they have expressed. We present an application on a real dataset following two different approaches, and a simulation study to test the model's performance. Simulations showed that the quality of the model performance increases when the number of rankings and objects increases. In addition, the performance is considerably amplified when the judges' characteristics have a high impact on their choices.

Refined moderation analysis with categorical outcomes in precision medicine.

Moderation analysis is an integral part of precision medicine research. Concerning moderation analysis with categorical outcomes, we start with an interesting observation, which shows that heterogeneous treatment effects could be equivalently estimated via a role exchange between the outcome and the treatment variable in logistic regression models. Hence two estimators of moderating effects can be obtained. We then established the joint asymptotic normality for the two estimators, on which basis refined inference can be made for moderation analysis. The improved precision is helpful in addressing the lack-of-power problem that is common in search of moderators. The above-mentioned results hold for both experimental and observational data. We investigate the proposed method by simulation and provide an illustration with data from a randomized trial on wart treatment.

Do automated digital health behaviour change interventions have a positive effect on self-efficacy? A systematic review and meta-analysis.

Self-efficacy is an important determinant of health behaviour. Digital interventions are a potentially acceptable and cost-effective way of delivering programmes of health behaviour change at scale. Whether behaviour change interventions work to increase self-efficacy in this context is unknown. This systematic review and meta-analysis sought to identify whether automated digital interventions are associated with positive changes in self-efficacy amongst non-clinical populations for five major health behaviours, and which BCTs are associated with that change. A systematic literature search identified 20 studies (n = 5624) that assessed changes in self-efficacy and were included in a random-effects meta-analysis. Interventions targeted: healthy eating (k = 4), physical activity (k = 9), sexual behaviour (k = 3) and smoking (k = 4). No interventions targeting alcohol use were identified. Overall, interventions had a small, positive effect on self-efficacy (g¯=0.190,CI[0.078;0.303]). The effect of interventions on self-efficacy did not differ as a function of health behaviour type (Q-between = 7.3704, p = .061, df = 3). Inclusion of the BCT 'information about social and environmental consequences' had a small, negative effect on self-efficacy (Δg¯=-0.297,Q=7.072,p=.008). Whilst this review indicates that digital interventions can be used to change self-efficacy, which techniques work best in this context is not clear.

Prevalence of anxiety disorders and subthreshold anxiety throughout later life: Systematic review and meta-analysis.

This systematic review and meta-analysis compared prevalence rates for subthreshold anxiety and anxiety disorders in adults aged 55+ and examined if these rates were associated with age. A systematic search and screening procedure resulted in 46 included articles. First, prevalence rates for subthreshold anxiety and anxiety disorders were statistically compared. Subthreshold panic, generalized anxiety and specific phobia were significantly more prevalent than the corresponding clinical disorders. In general, subthreshold anxiety appeared to be at least similarly prevalent to anxiety disorders, although firm conclusions are precluded due to the small number of samples that could be included in the analyses and the large heterogeneity between the reported prevalence rates. Second, using subgroup analyses, pooled prevalence rates for four age groups of older adults (55-64, 65-74, 75-84, 85+) were compared. For specific phobia, the 75-84 and 85+ groups had significantly lower prevalence rates than the 55-64 and 65-74 groups. Posttraumatic stress disorder was significantly more prevalent in the 55-64 group than in the other age groups, and lowest in the 85+ group. No other significant differences between age groups were found. The association between later life subthreshold anxiety and age could not be examined due to a lack of reported information. The main limitation of this study is the small number of samples in the analyses, which limits their power and generalizability. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Multiple moderator meta-analysis using the R-package Meta-CART.

In meta-analysis, heterogeneity often exists between studies. Knowledge about study features (i.e., moderators) that can explain the heterogeneity in effect sizes can be useful for researchers to assess the effectiveness of existing interventions and design new potentially effective interventions. When there are multiple moderators, they may amplify or attenuate each other's effect on treatment effectiveness. However, in most meta-analysis studies, interaction effects are neglected due to the lack of appropriate methods. The method meta-CART was recently proposed to identify interactions between multiple moderators. The analysis result is a tree model in which the studies are partitioned into more homogeneous subgroups by combinations of moderators. This paper describes the R-package metacart, which provides user-friendly functions to conduct meta-CART analyses in R. This package can fit both fixed- and random-effects meta-CART, and can handle dichotomous, categorical, ordinal and continuous moderators. In addition, a new look ahead procedure is presented. The application of the package is illustrated step-by-step using diverse examples.

Moderators of the effect of guided online self-help for people with HIV and depressive symptoms.

The goal of the study was to investigate moderators of intervention effect of a guided Internet-based self-help cognitive behavioral intervention for people with HIV and depressive symptoms. This study was part of a randomized controlled trial where the intervention was found to be effective in reducing depressive symptoms, compared to an attention-only control group. Demographic characteristics (e.g., age), HIV characteristics (e.g., duration of HIV), and psychological characteristics (e.g., coping self-efficacy) were investigated as potential moderators of intervention effect. In 2015, 188 people with HIV and depressive symptoms were included in the study: 97 were randomized to the intervention group and 91 to the control group. Two moderators of intervention effect were found: coping self-efficacy and baseline depression severity. Participants with low coping self-efficacy and baseline depression severity improved more in the intervention group than in the control group, and participants with high coping self-efficacy and baseline depression severity improved in both groups. The results indicate that the intervention may be provided to all people with HIV and depressive symptoms. It may be especially important for people with HIV and low coping self-efficacy to start with the intervention since they show less improvement in the control group with only attention. Trial registration: Nederlands Trialregister NTR5407, September 11, 2015.

Added value of Mindfulness-Based Cognitive Therapy for Depression: A Tree-based Qualitative Interaction Analysis.

AIM: To identify moderators of treatment effect for Mindfulness-Based Cognitive Therapy (MBCT) versus Treatment As Usual (TAU) in depressed patients. METHODS: An individual patient data-analysis was performed on three randomized-controlled trials, investigating the effect of MBCT + TAU versus TAU alone (N = 292). Patients were either in (partial) remission, currently depressed or had chronic, treatment-resistant depression. Outcomes were depressive symptoms and quality of life. The QUalitative INteraction Trees (QUINT) method was used to identify subgroups that benefited more from either condition. RESULTS: MBCT + TAU outperformed TAU in reducing depressive symptoms. For both conditions, the effect of baseline depressive symptoms on post-treatment depressive symptoms was curvilinear. QUINT analyses revealed that MBCT + TAU was more beneficial than TAU for patients with an earlier onset and higher rumination levels in terms of depressive symptom reduction and for patients with a lower quality of life in terms of improving quality of life. CONCLUSIONS: The results suggest that MBCT might be more beneficial for those with earlier onset and higher levels of rumination and for patients with a lower quality of life. Sophisticated analytical techniques such as QUINT can be used in future research to improve personalized assignment of MBCT to patients. Long-term outcome could also be integrated in this.

Predictive validity of developmental milestones for detecting limited intellectual functioning.

Developmental milestones are commonly used in child health care, although from many milestones the predictive validity has not been adequately assessed. We aimed to determine the predictive validity of 75 developmental milestones for detecting limited intellectual functioning that can be obtained before the age of 4 years. We performed a case-control study with 148 children aged 5-10 years with limited intellectual functioning (IQ 50-69), who were in special education (cases) and a random sample of 300 children aged 5-10 years who were in regular elementary education (controls). Developmental milestones scores were retrieved from Child Healthcare files. We calculated sensitivity, specificity, positive likelihood ratios (LR+) and diagnostic odds ratios (DOR) for limited intellectual functioning. The LR+ determines whether a test result changes the probability that a condition exists. Given the prevalence of intellectual disability (1-3%), we considered that an LR+ > 10 would be clinically useful, as it increases the a priori probability of limited intellectual functioning from 2% to a posteriori probability of at least 17%. Out of 75 assessed milestones, 50 were included in the analysis. We found nine milestones to have a significant adjusted (for socio-economic status and prematurity) DOR > 1 and a significant LR+ > 10 (assessment age in months between brackets): 'says "dada-baba‴ (9), 'balances head well while sitting' (9), 'sits on buttocks while legs stretched' (9), 'babbles while playing' (12), 'sits in stable position without support' (12), 'walks well alone' (24), 'says "sentences" of 3 or more words' (36), 'places 3 forms in form-box' (36) and 'copies circle' (48). Sensitivities of these 9 milestones varied from 8-54%, specificities of these 9 milestones varied from 95-100%. Combining these milestones at 9, 12, and 36 months respectively resulted in sensitivities of 27-60% and specificities of 94-99%. These nine developmental milestones have substantial predictive validity for limited intellectual functioning.

A flexible approach to identify interaction effects between moderators in meta-analysis.

In meta-analytic studies, there are often multiple moderators available (eg, study characteristics). In such cases, traditional meta-analysis methods often lack sufficient power to investigate interaction effects between moderators, especially high-order interactions. To overcome this problem, meta-CART was proposed: an approach that applies classification and regression trees (CART) to identify interactions, and then subgroup meta-analysis to test the significance of moderator effects. The aim of this study is to improve meta-CART upon two aspects: 1) to integrate the two steps of the approach into one and 2) to consistently take into account the fixed-effect or random-effects assumption in both the the interaction identification and testing process. For fixed effect meta-CART, weights are applied, and subgroup analysis is adapted. For random effects meta-CART, a new algorithm has been developed. The performance of the improved meta-CART was investigated via an extensive simulation study on different types of moderator variables (ie, dichotomous, nominal, ordinal, and continuous variables). The simulation results revealed that the new method can achieve satisfactory performance (power greater than 0.80 and Type I error less than 0.05) if appropriate pruning rule is applied and the number of studies is large enough. The required minimum number of studies ranges from 40 to 120 depending on the complexity and strength of the interaction effects, the within-study sample size, the type of moderators, and the residual heterogeneity.

Interventions to Promote Healthy Eating, Physical Activity and Smoking in Low-Income Groups: a Systematic Review with Meta-Analysis of Behavior Change Techniques and Delivery/Context.

PURPOSE: Healthy eating, physical activity and smoking interventions for low-income groups may have small, positive effects. Identifying effective intervention components could guide intervention development. This study investigated which content and delivery components of interventions were associated with increased healthy behavior in randomised controlled trials (RCTs) for low-income adults. METHOD: Data from a review showing intervention effects in 35 RCTs containing 45 interventions with 17,000 participants were analysed to assess associations with behavior change techniques (BCTs) and delivery/context components from the template for intervention description and replication (TIDieR) checklist. The associations of 46 BCTs and 14 delivery/context components with behavior change (measures of healthy eating, physical activity and smoking cessation) were examined using random effects subgroup meta-analyses. Synergistic effects of components were examined using classification and regression trees (meta-CART) analyses based on both fixed and random effects assumptions. RESULTS: For healthy eating, self-monitoring, delivery through personal contact, and targeting multiple behaviors were associated with increased effectiveness. Providing feedback, information about emotional consequences, or using prompts and cues were associated with reduced effectiveness. In synergistic analyses, interventions were most effective without feedback, or with self-monitoring excluding feedback. More effective physical activity interventions included behavioral practice/rehearsal or instruction, focussed solely on physical activity or took place in home/community settings. Information about antecedents was associated with reduced effectiveness. In synergistic analyses, interventions were most effective in home/community settings with instruction. No associations were identified for smoking. CONCLUSION: This study identified BCTs and delivery/context components, individually and synergistically, linked to increased and reduced effectiveness of healthy eating and physical activity interventions. The identified components should be subject to further experimental study to help inform the development effective behavior change interventions for low-income groups to reduce health inequalities.

Training staff to promote self-management in people with intellectual disabilities.

BACKGROUND: People with intellectual disabilities have increasing difficulties managing their daily affairs. This study examined the effectiveness of a staff training, which teaches staff to promote self-management in people with intellectual disabilities. METHOD: Effectiveness was assessed with questionnaires addressing clients' (n = 26) independence and self-reliance, support needs and challenging behaviour, using a pre-posttest control group design. Additionally, focus groups were conducted with trained staff members 6 months after the training. RESULTS: In the long term, the intervention group showed a significant increase in independence and self-reliance, in contrast to the comparison group. No effect was found on support needs and challenging behaviour. Trained staff members reported limited benefits of the training, but had noticed changes in their attitude and method of working afterwards. CONCLUSIONS: Further self-management research is required to investigate how independence and self-reliance can be promoted more effectively in this population. Future trainings should carefully consider their content, format, and implementation.

The Benefits of Psychosocial Interventions for Mental Health in People Living with HIV: A Systematic Review and Meta-analysis.

In this systematic review and meta-analysis we investigated the effectiveness of different psychosocial treatments for people living with HIV (PLWH) and mental health problems. Additionally, characteristics that may influence the effectiveness of a treatment (e.g., treatment duration) were studied. PubMed, PsycINFO and Embase were searched for randomized controlled trials on psychosocial interventions for PLWH. Depression, anxiety, quality of life, and psychological well-being were investigated as treatment outcome measures. Sixty-two studies were included in the meta-analysis. It was found that psychosocial interventions for PLWH had a small positive effect on mental health (g = 0.19, 95% CI [0.13, 0.25]). Furthermore, there was evidence for publication bias. Six characteristics influenced the effectiveness of a treatment for depression. For example, larger effects were found for studies with psychologists as treatment providers. To conclude, this systematic review and meta-analysis suggests that psychosocial interventions have a beneficial effect for PLWH with mental health problems.

Meta-CART: A tool to identify interactions between moderators in meta-analysis.

In the framework of meta-analysis, moderator analysis is usually performed only univariately. When several study characteristics are available that may account for treatment effect, standard meta-regression has difficulties in identifying interactions between them. To overcome this problem, meta-CART has been proposed: an approach that applies classification and regression trees (CART) to identify interactions, and then subgroup meta-analysis to test the significance of moderator effects. The previous version of meta-CART has its shortcomings: when applying CART, the sample sizes of studies are not taken into account, and the effect sizes are dichotomized around the median value. Therefore, this article proposes new meta-CART extensions, weighting study effect sizes by their accuracy, and using a regression tree to avoid dichotomization. In addition, new pruning rules are proposed. The performance of all versions of meta-CART was evaluated via a Monte Carlo simulation study. The simulation results revealed that meta-regression trees with random-effects weights and a 0.5-standard-error pruning rule perform best. The required sample size for meta-CART to achieve satisfactory performance depends on the number of study characteristics, the magnitude of the interactions, and the residual heterogeneity.

Effective self-regulation change techniques to promote mental wellbeing among adolescents: a meta-analysis.

Mental wellbeing is influenced by self-regulation processes. However, little is known on the efficacy of change techniques based on self-regulation to promote mental wellbeing. The aim of this meta-analysis is to identify effective self-regulation techniques (SRTs) in primary and secondary prevention interventions on mental wellbeing in adolescents. Forty interventions were included in the analyses. Techniques were coded into nine categories of SRTs. Meta-analyses were conducted to identify the effectiveness of SRTs, examining three different outcomes: internalising behaviour, externalising behaviour, and self-esteem. Primary interventions had a small-to-medium ([Formula: see text] = 0.16-0.29) on self-esteem and internalising behaviour. Secondary interventions had a medium-to-large short-term effect (average [Formula: see text] = 0.56) on internalising behaviour and self-esteem. In secondary interventions, interventions including asking for social support [Formula: see text] 95% confidence interval, CI = 1.11-1.98) had a great effect on internalising behaviour. Interventions including monitoring and evaluation had a greater effect on self-esteem [Formula: see text] 95% CI = 0.21-0.57). For primary interventions, there was not a single SRT that was associated with a greater intervention effect on internalising behaviour or self-esteem. No effects were found for externalising behaviours. Self-regulation interventions are moderately effective at improving mental wellbeing among adolescents. Secondary interventions promoting 'asking for social support' and promoting 'monitoring and evaluation' were associated with improved outcomes. More research is needed to identify other SRTs or combinations of SRTs that could improve understanding or optimise mental wellbeing interventions.

Modeling Caries Experience: Advantages of the Use of the Hurdle Model.

In dental epidemiology, the decayed (D), missing (M), and filled (F) teeth or surfaces index (DFM index) is a frequently used measure. The DMF index is characterized by a strongly positive skewed distribution with a large stack of zero counts for those individuals without caries experience. Therefore, standard generalized linear models often lead to a poor fit. The hurdle regression model is a highly suitable class to model a DMF index, but its use is subordinated. We aim to overcome the gap between the suitability of the hurdle model to fit DMF indices and the frequency of its use in caries research. A theoretical introduction to the hurdle model is provided, and an extensive comparison with the zero-inflated model is given. Using an illustrative data example, both types of models are compared, with a special focus on interpretation of their parameters. Accompanying R code and example data are provided as online supplementary material.

Physical activity and relaxation in the work setting to reduce the need for recovery: what works for whom?

BACKGROUND: To recover from work stress, a worksite health program aimed at improving physical activity and relaxation may be valuable. However, not every program is effective for all participants, as would be expected within a "one size fits all" approach. The effectiveness of how the program is delivered may differ across individuals. The aim of this study was to identify subgroups for whom one intervention may be better suited than another by using a new method called QUalitative INteraction Trees (QUINT). METHODS: Data were used from the "Be Active & Relax" study, in which 329 office workers participated. Two delivery modes of a worksite health program were given, a social environmental intervention (group motivational interviewing delivered by team leaders) and a physical environmental intervention (environmental modifications). The main outcome was change in Need for Recovery (NFR) from baseline to 12 month follow-up. The QUINT method was used to identify subgroups that benefitted more from either type of delivery mode, by incorporating moderator variables concerning sociodemographic, health, home, and work-related characteristics of the participants. RESULTS: The mean improvement in NFR of younger office workers in the social environmental intervention group was significantly higher than younger office workers who did not receive the social environmental intervention (10.52; 95 % CI: 4.12, 16.92). Furthermore, the mean improvement in NFR of older office workers in the social environmental intervention group was significantly lower than older office workers who did not receive the social environmental intervention ( -10.65; 95 % CI: -19.35, -1.96). The results for the physical environmental intervention indicated that the mean improvement in NFR of office workers (regardless of age) who worked fewer hours overtime was significantly higher when they had received the physical environmental intervention than when they had not received this type of intervention (7.40; 95 % CI: 0.99, 13.81). Finally, for office workers who worked more hours overtime there was no effect of the physical environmental intervention. CONCLUSIONS: The results suggest that a social environmental intervention might be more beneficial for younger workers, and a physical environmental intervention might be more beneficial for employees with a few hours overtime to reduce the NFR. TRIAL REGISTRATION: NTR2553.