Focus: Health Equity: The Sick Bias

This perspectives piece shares the experience of a trainee during the COVID-19 pandemic as it pertains to initial patient evaluations and the subsequent impact they have on patient outcomes. Specifically highlighting the value of approaching every patient as sick before deeming them as well – this approach to triaging is defined as a “sick bias” throughout the piece. Unfortunately, this initial evaluation can be influenced by explicit and implicit biases of the provider that highlight health inequities within their patient’s care.     

Money Walks: Implicit Mobility Behavior and Financial Well-Being

Traditional financial decision systems (e.g. credit) had to rely on explicit individual traits like age, gender, job type, and marital status, while being oblivious to spatio-temporal mobility or the habits of the individual involved. Emerging trends in geo-aware and mobile payment systems, and the resulting “big data,” present an opportunity to study human consumption patterns across space and time. Taking inspiration from animal behavior studies that have reported significant interconnections between animal spatio-temporal “foraging” behavior and their life outcomes, we analyzed a corpus of hundreds of thousands of human economic transactions and found that financial outcomes for individuals are intricately linked with their spatio-temporal traits like exploration, engagement, and elasticity. Such features yield models that are 30% to 49% better at predicting future financial difficulties than the comparable demographic models.     

Psychological Distress and Coping amongst Higher Education Students: A Mixed Method Enquiry

Background

Psychological distress among higher education students is of global concern. Students on programmes with practicum components such as nursing and teacher education are exposed to additional stressors which may further increase their risk for psychological distress. The ways in which these students cope with distress has potential consequences for their health and academic performance. An in-depth understanding of how nursing/midwifery and teacher education students experience psychological distress and coping is necessary to enable higher education providers to adequately support these students.

Methods

This mixed method study was employed to establish self-reported psychological distress (General Health Questionnaire), coping processes (Ways of Coping Questionnaire) and lifestyle behaviour (Lifestyle Behaviour Questionnaire) of a total sample (n = 1557) of undergraduate nursing/midwifery and teacher education students in one university in Ireland. Individual interviews (n = 59) provided an in-depth understanding of students experiences of psychological distress and coping.

Results

A significant percentage (41.9%) of respondents was psychologically distressed. The factors which contributed to their distress, included study, financial, living and social pressures. Students used varied coping strategies including seeking social support, problem solving and escape avoidance. The positive relationship between elevated psychological distress and escape avoidance behaviours including substance use (alcohol, tobacco and cannabis) and unhealthy diet is of particular concern. Statistically significant relationships were identified between “escape-avoidance” and gender, age, marital status, place of residence, programme/year of study and lifestyle behaviours such as diet, substance use and physical inactivity.

Conclusion

The paper adds to existing research by illuminating the psychological distress experienced by undergraduate nursing/midwifery and teacher education students. It also identifies their distress, maladaptive coping and the relationship to their lifestyle behaviours. The findings can inform strategies to minimise student distress and maladaptive coping during college and in future professional years.     

Outcomes for patients with the same disease treated inside and outside of randomized trials: a systematic review and meta-analysis

Background:

It is unclear whether participation in a randomized controlled trial (RCT), irrespective of assigned treatment, is harmful or beneficial to participants. We compared outcomes for patients with the same diagnoses who did (“insiders”) and did not (“outsiders”) enter RCTs, without regard to the specific therapies received for their respective diagnoses.

Methods:

By searching the MEDLINE (1966–2010), Embase (1980–2010), CENTRAL (1960–2010) and PsycINFO (1880–2010) databases, we identified 147 studies that reported the health outcomes of “insiders” and a group of parallel or consecutive “outsiders” within the same time period. We prepared a narrative review and, as appropriate, meta-analyses of patients’ outcomes.

Results:

We found no clinically or statistically significant differences in outcomes between “insiders” and “outsiders” in the 23 studies in which the experimental intervention was ineffective (standard mean difference in continuous outcomes −0.03, 95% confidence interval [CI] −0.1 to 0.04) or in the 7 studies in which the experimental intervention was effective and was received by both “insiders” and “outsiders” (mean difference 0.04, 95% CI −0.04 to 0.13). However, in 9 studies in which an effective intervention was received only by “insiders,” the “outsiders” experienced significantly worse health outcomes (mean difference −0.36, 95% CI −0.61 to −0.12).

Interpretation:

We found no evidence to support clinically important overall harm or benefit arising from participation in RCTs. This conclusion refutes earlier claims that trial participants are at increased risk of harm.When people are asked to participate in a randomized controlled trial (RCT), it is natural for them to ask several questions in return. How safe are these treatments? How many extra visits and tests must I undergo? Will the researchers keep my family doctor informed about what’s going on? What outcomes are to be measured, and do they include ones that are of interest to me as a patient?These multiple questions can be summarized as follows: Would I fare better being treated within the trial (as an “insider”) or in routine clinical care outside it (as an “outsider”)? Patients may ask this question in 1 of 2 ways. The first is highly specific: “Am I better off receiving this specific treatment as an insider or as an outsider?” Alternatively, they might ask a more general question: “Am I better off having my illness managed, regardless of the specific treatment I would receive, as an insider or as an outsider?” These questions are highly appropriate, and both deserve to be asked and answered,^1,2 especially given that nonsystematic reviews have suggested a possible “inclusion benefit” from participating in trials.³These 2 specific patient questions are analogous to those posed by researchers asking whether treatments do more good than harm when applied under “ideal” circumstances (in explanatory trials) or in the “real world” of routine health care (in pragmatic trials). Vist and colleagues answered the explanatory question when their earlier review⁴ found no advantage or disadvantage from receiving the same treatment inside or outside an RCT. Left unanswered, however, was the broader, more pragmatic question. In our experience, trial participants are often offered new, as-yet-untested treatments that would not be available to them outside the trial. This review looks at the dilemma faced by these patients, which needs to be addressed before general conclusions can be drawn about trial safety.     

Does Marriage Make Us Healthier? Inter-Country Comparative Evidence from China,Japan, and Korea

Objectives

This study focuses on East Asian countries and investigates the difference in the marriage premium on the health-marriage protection effect (MPE) between younger and older generations and the intra-couple education concordance effect (ECE) on the health of married individuals. This study used inter-country comparative data from China, Japan, and Korea.

Methods

This study focused on individuals (n = 7,938) in China, Japan, and Korea who were sampled from the 2010 East Asian Social Survey. To investigate MPE and ECE, four health indicators were utilized: a physical and mental components summary (PCS and MCS), self-rated health status (D_self), and happiness level (D_happy). Ordinary least squares regression was conducted by country- and gender-specific subsamples.

Results

We found that the MPE on PCS, MCS, and D_self was more significant for the older generation than for the younger generation in both China and Japan, whereas the results were inconclusive in Korea. With regard to the ECE on happiness (D_happy), for both men and women, couples tend to be happier when both the husband and the wife are well educated (“higher balanced marriage”) compared to couples with a lower level of educational achievement (“lower balanced marriage”). Significant benefits from a “higher balanced marriage” on MCS and D_self were observed for women only. In contrast, no statistically significant differences in health status were observed between “higher balanced marriage” couples and couples with different levels of educational achievements (“upward marriage” or “downward marriage”).

Conclusions

This study found that (1) the MPE was more significant for the older generation, and (2) the health gap, particularly the happiness gap, between higher- and lower-balanced married couples was significant. The inter-country comparative findings are useful to explain how the role of marriage (and therefore of family) on health has been diluted due to the progress of industrialization and modernization.     

Economic Analysis of the Impact of Overseas and Domestic Treatment and Screening Options for Intestinal Helminth Infection among US-Bound Refugees from Asia

BackgroundMany U.S.-bound refugees travel from countries where intestinal parasites (hookworm, Trichuris trichuria, Ascaris lumbricoides, and Strongyloides stercoralis) are endemic. These infections are rare in the United States and may be underdiagnosed or misdiagnosed, leading to potentially serious consequences. This evaluation examined the costs and benefits of combinations of overseas presumptive treatment of parasitic diseases vs. domestic screening/treating vs. no program.MethodsAn economic decision tree model terminating in Markov processes was developed to estimate the cost and health impacts of four interventions on an annual cohort of 27,700 U.S.-bound Asian refugees: 1) “No Program,” 2) U.S. “Domestic Screening and Treatment,” 3) “Overseas Albendazole and Ivermectin” presumptive treatment, and 4) “Overseas Albendazole and Domestic Screening for Strongyloides”. Markov transition state models were used to estimate long-term effects of parasitic infections. Health outcome measures (four parasites) included outpatient cases, hospitalizations, deaths, life years, and quality-adjusted life years (QALYs).ResultsThe “No Program” option is the least expensive ($165,923 per cohort) and least effective option (145 outpatient cases, 4.0 hospitalizations, and 0.67 deaths discounted over a 60-year period for a one-year cohort). The “Overseas Albendazole and Ivermectin” option ($418,824) is less expensive than “Domestic Screening and Treatment” ($3,832,572) or “Overseas Albendazole and Domestic Screening for Strongyloides” ($2,182,483). According to the model outcomes, the most effective treatment option is “Overseas Albendazole and Ivermectin,” which reduces outpatient cases, deaths and hospitalization by around 80% at an estimated net cost of $458,718 per death averted, or $2,219/$24,036 per QALY/life year gained relative to “No Program”.DiscussionOverseas presumptive treatment for U.S.-bound refugees is a cost-effective intervention that is less expensive and at least as effective as domestic screening and treatment programs. The addition of ivermectin to albendazole reduces the prevalence of chronic strongyloidiasis and the probability of rare, but potentially fatal, disseminated strongyloidiasis.     

Comparative Phylogenomics and Evolution of the Brucellae Reveal a Path to Virulence

Brucella species include important zoonotic pathogens that have a substantial impact on both agriculture and human health throughout the world. Brucellae are thought of as “stealth pathogens” that escape recognition by the host innate immune response, modulate the acquired immune response, and evade intracellular destruction. We analyzed the genome sequences of members of the family Brucellaceae to assess its evolutionary history from likely free-living soil-based progenitors into highly successful intracellular pathogens. Phylogenetic analysis split the genus into two groups: recently identified and early-dividing “atypical” strains and a highly conserved “classical” core clade containing the major pathogenic species. Lateral gene transfer events brought unique genomic regions into Brucella that differentiated them from Ochrobactrum and allowed the stepwise acquisition of virulence factors that include a type IV secretion system, a perosamine-based O antigen, and systems for sequestering metal ions that are absent in progenitors. Subsequent radiation within the core Brucella resulted in lineages that appear to have evolved within their preferred mammalian hosts, restricting their virulence to become stealth pathogens capable of causing long-term chronic infections.     

Local Modelling Techniques for Assessing Micro-Level Impacts of Risk Factors in Complex Data: Understanding Health and Socioeconomic Inequalities in Childhood Educational Attainments

Although inequalities in health and socioeconomic status have an important influence on childhood educational performance, the interactions between these multiple factors relating to variation in educational outcomes at micro-level is unknown, and how to evaluate the many possible interactions of these factors is not well established. This paper aims to examine multi-dimensional deprivation factors and their impact on childhood educational outcomes at micro-level, focusing on geographic areas having widely different disparity patterns, in which each area is characterised by six deprivation domains (Income, Health, Geographical Access to Services, Housing, Physical Environment, and Community Safety). Traditional health statistical studies tend to use one global model to describe the whole population for macro-analysis. In this paper, we combine linked educational and deprivation data across small areas (median population of 1500), then use a local modelling technique, the Takagi-Sugeno fuzzy system, to predict area educational outcomes at ages 7 and 11. We define two new metrics, “Micro-impact of Domain” and “Contribution of Domain”, to quantify the variations of local impacts of multidimensional factors on educational outcomes across small areas. The two metrics highlight differing priorities. Our study reveals complex multi-way interactions between the deprivation domains, which could not be provided by traditional health statistical methods based on single global model. We demonstrate that although Income has an expected central role, all domains contribute, and in some areas Health, Environment, Access to Services, Housing and Community Safety each could be the dominant factor. Thus the relative importance of health and socioeconomic factors varies considerably for different areas, depending on the levels of each of the other factors, and therefore each component of deprivation must be considered as part of a wider system. Childhood educational achievement could benefit from policies and intervention strategies that are tailored to the local geographic areas'' profiles.     

Predictive Factors of Patient Satisfaction with Pharmacy Services in South Korea: A Cross-Sectional Study of National Level Data

Objectives

Patient satisfaction has emerged as a prerequisite to improving patients’ health behaviors leading to better health care outcomes. This study was to identify predictive determinants for patient satisfaction with pharmacy services using national-level data.

Methods

A cross-sectional evaluation was conducted using 2008 Korean National Health and Nutrition Examination Survey (KNHANES) data. To assess the predictive factors for patient satisfaction with pharmacy services, an ordinal logistic regression model was conducted adjusting for patient characteristics, clinical comorbidities, and perception of health.

Results

A total of 9,744 people, a representative sample of 48.2 million Koreans, participated in the 2008 KNHANES, of whom 2,188 (23.6%) reported visits to pharmacy within the last 2 weeks prior to the survey. Of the patients who visited the pharmacy, 74.6% reported to be either “very satisfied” or “satisfied,” and 25.4% responded as being “neutral,” “dissatisfied,” or “very dissatisfied.” A multivariate ordinal logistic regression analysis with weighted observations revealed that patients with fair perception of health (adjusted OR 1.32; 95% CI 1.01–1.74; p<0.05) and those with middle to low family incomes (adjusted OR 1.34; 95% CI 1.02–1.76; p<0.05) were more likely to be satisfied with pharmacy services, and employment-based insurers were less likely to be satisfied with pharmacy services (adjusted OR 0.80; 95% CI 0.65–0.97; p<0.05).

Conclusion

Our findings indicated that three out of four patients expressed satisfaction toward pharmacy services. Middle to low family incomes, fair perception of health, and employee insured individuals were significant predictors of patient satisfaction with pharmacy services.     

Psychological and Social Work Factors as Predictors of Mental Distress: A Prospective Study

Studies exploring psychological and social work factors in relation to mental health problems (anxiety and depression) have mainly focused on a limited set of exposures. The current study investigated prospectively a broad set of specific psychological and social work factors as predictors of potentially clinically relevant mental distress (anxiety and depression), i.e. “caseness” level of distress. Employees were recruited from 48 Norwegian organizations, representing a wide variety of job types. A total of 3644 employees responded at both baseline and at follow-up two years later. Respondents were distributed across 832 departments within the 48 organizations. Nineteen work factors were measured. Two prospective designs were tested: (i) with baseline predictors and (ii) with average exposure over time ([T1+T2]/2) as predictors. Random intercept logistic regressions were conducted to account for clustering of the data. Baseline “cases” were excluded (n = 432). Age, sex, skill level, and mental distress as a continuous variable at T1 were adjusted for. Fourteen of 19 factors showed some prospective association with mental distress. The most consistent risk factor was role conflict (highest odds ratio [OR] 2.08, 99% confidence interval [CI]: 1.45–3.00). The most consistent protective factors were support from immediate superior (lowest OR 0.56, 99% CI: 0.43–0.72), fair leadership (lowest OR 0.52, 99% CI: 0.40–0.68), and positive challenge (lowest OR 0.60, 99% CI: 0.41–0.86). The present study demonstrated that a broad set of psychological and social work factors predicted mental distress of potential clinical relevance. Some of the most consistent predictors were different from those traditionally studied. This highlights the importance of expanding the range of factors beyond commonly studied concepts like the demand-control model and the effort-reward imbalance model.     

Antagonistic Parent-Offspring Co-Adaptation

Background

In species across taxa, offspring have means to influence parental investment (PI). PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear.

Methodology/Principal Findings

In contrast to previous theory that largely uses a static approach to predict how “offspring individuals” and “parental individuals” should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents.

Conclusions/Significance

We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.     

FliZ Is a Global Regulatory Protein Affecting the Expression of Flagellar and Virulence Genes in Individual Xenorhabdus nematophila Bacterial Cells

Heterogeneity in the expression of various bacterial genes has been shown to result in the presence of individuals with different phenotypes within clonal bacterial populations. The genes specifying motility and flagellar functions are coordinately regulated and form a complex regulon, the flagellar regulon. Complex interplay has recently been demonstrated in the regulation of flagellar and virulence gene expression in many bacterial pathogens. We show here that FliZ, a DNA-binding protein, plays a key role in the insect pathogen, Xenorhabdus nematophila, affecting not only hemolysin production and virulence in insects, but efficient swimming motility. RNA-Seq analysis identified FliZ as a global regulatory protein controlling the expression of 278 Xenorhabdus genes either directly or indirectly. FliZ is required for the efficient expression of all flagellar genes, probably through its positive feedback loop, which controls expression of the flhDC operon, the master regulator of the flagellar circuit. FliZ also up- or downregulates the expression of numerous genes encoding non-flagellar proteins potentially involved in key steps of the Xenorhabdus lifecycle. Single-cell analysis revealed the bimodal expression of six identified markers of the FliZ regulon during exponential growth of the bacterial population. In addition, a combination of fluorescence-activated cell sorting and RT-qPCR quantification showed that this bimodality generated a mixed population of cells either expressing (“ON state”) or not expressing (“OFF state”) FliZ-dependent genes. Moreover, studies of a bacterial population exposed to a graded series of FliZ concentrations showed that FliZ functioned as a rheostat, controlling the rate of transition between the “OFF” and “ON” states in individuals. FliZ thus plays a key role in cell fate decisions, by transiently creating individuals with different potentials for motility and host interactions.     

Disparate movement behavior and feeding ecology in sympatric ecotypes of Atlantic cod

Coexistence of ecotypes, genetically divergent population units, is a widespread phenomenon, potentially affecting ecosystem functioning and local food web stability. In coastal Skagerrak, Atlantic cod (Gadus morhua) occur as two such coexisting ecotypes. We applied a combination of acoustic telemetry, genotyping, and stable isotope analysis to 72 individuals to investigate movement ecology and food niche of putative local “Fjord” and putative oceanic “North Sea” ecotypes—thus named based on previous molecular studies. Genotyping and individual origin assignment suggested 41 individuals were Fjord and 31 were North Sea ecotypes. Both ecotypes were found throughout the fjord. Seven percent of Fjord ecotype individuals left the study system during the study while 42% of North Sea individuals left, potentially homing to natal spawning grounds. Home range sizes were similar for the two ecotypes but highly variable among individuals. Fjord ecotype cod had significantly higher δ¹³C and δ¹⁵N stable isotope values than North Sea ecotype cod, suggesting they exploited different food niches. The results suggest coexisting ecotypes may possess innate differences in feeding and movement ecologies and may thus fill different functional roles in marine ecosystems. This highlights the importance of conserving interconnected populations to ensure stable ecosystem functioning and food web structures.     

Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis

Objective To quantify the association between stressful life events and exacerbations of multiple sclerosis.Data sources PubMed, PsychInfo, and Psychological Abstracts searched for empirical papers from 1965 to February 2003 with terms “stress”, “trauma”, and “multiple sclerosis”.Review methods Three investigators independently reviewed papers for inclusion/exclusion criteria and extracted the relevant data, including methods, sample statistics, and outcomes.Results Of 20 studies identified, 14 were included. The meta-analysis showed a significant increase in risk of exacerbation in multiple sclerosis after stressful life events, with a weighted average effect size of d = 0.53 (95% confidence interval 0.40 to 0.65), P < 0.0001. The studies were homogenous, Q = 16.62, P = 0.22, I² = 21.8%. Neither sampling nor study methods had any effect on study outcomes.Conclusions There is a consistent association between stressful life events and subsequent exacerbation in multiple sclerosis. However these data do not allow the linking of specific stressors to exacerbations nor should they be used to infer that patients are responsible for their exacerbations. Investigation of the psychological, neuroendocrine, and immune mediators of stressful life events on exacerbation may lead to new behavioural and pharmacological strategies targeting potential links between stress and exacerbation.     

Does General Motivation Energize Financial Reward-Seeking Behavior? Evidence from an Effort Task

We aimed to predict how hard subjects work for financial rewards from their general trait and state reward-motivation. We specifically asked 1) whether individuals high in general trait “reward responsiveness” work harder 2) whether task-irrelevant cues can make people work harder, by increasing general motivation. Each trial of our task contained a 1 second earning interval in which male subjects earned money for each button press. This was preceded by one of three predictive cues: an erotic picture of a woman, a man, or a geometric figure. We found that individuals high in trait “reward responsiveness” worked harder and earned more, irrespective of the predictive cue. Because female predictive cues are more rewarding, we expected them to increase general motivation in our male subjects and invigorate work, but found a more complex pattern.     

Violence Affects Physical and Mental Health Differently: The General Population Based Troms? Study

This general population-based study examined associations between violence and mental health, musculoskeletal pain, and early disability pension. The prevalence and consequences of good vs. poor adjustment (resilience vs. vulnerability) following encounters with violence were also examined. Data were based on the sixth wave of the “Tromsø Study” (N = 12,981; 65.7% response rate, 53.4% women, M-age = 57.5 years, SD-age = 12.7 years). Self-reported data on psychological (threats) and physical violence (beaten/kicked), mental health (anxiety/depression), musculoskeletal pain (MSP), and granting of disability pension (DP) were collected. Men suffered more violent events during childhood than women did, and vice versa during adulthood. Psychological violence implied poorer mental health and slightly more MSP than physical violence. The risk of MSP was highest for violence occurring during childhood in women and during the last year for men. A dose-response relationship between an increasing number of violent encounters and poorer health was observed. About 58% of individuals reported no negative impact of violence (hence, resilience group), whereas 42% considered themselves as more vulnerable following encounters with violence. Regression analyses indicated comparable mental health but slightly more MSP in the resilience group compared to the unexposed group, whereas the vulnerable group had significantly worse health overall and a higher risk of early granting of DP. Resilience is not an all-or-nothing matter, as physical ailments may characterize individuals adapting well following encounters with violence.     

Characterization of the Oral Fungal Microbiome (Mycobiome) in Healthy Individuals

The oral microbiome–organisms residing in the oral cavity and their collective genome–are critical components of health and disease. The fungal component of the oral microbiota has not been characterized. In this study, we used a novel multitag pyrosequencing approach to characterize fungi present in the oral cavity of 20 healthy individuals, using the pan-fungal internal transcribed spacer (ITS) primers. Our results revealed the “basal” oral mycobiome profile of the enrolled individuals, and showed that across all the samples studied, the oral cavity contained 74 culturable and 11 non-culturable fungal genera. Among these genera, 39 were present in only one person, 16 genera were present in two participants, and 5 genera were present in three people, while 15 genera (including non-culturable organisms) were present in ≥4 (20%) participants. Candida species were the most frequent (isolated from 75% of participants), followed by Cladosporium (65%), Aureobasidium, Saccharomycetales (50% for both), Aspergillus (35%), Fusarium (30%), and Cryptococcus (20%). Four of these predominant genera are known to be pathogenic in humans. The low-abundance genera may represent environmental fungi present in the oral cavity and could simply be spores inhaled from the air or material ingested with food. Among the culturable genera, 61 were represented by one species each, while 13 genera comprised between 2 and 6 different species; the total number of species identified were 101. The number of species in the oral cavity of each individual ranged between 9 and 23. Principal component (PCO) analysis of the obtained data set followed by sample clustering and UniFrac analysis revealed that White males and Asian males clustered differently from each other, whereas both Asian and White females clustered together. This is the first study that identified the “basal mycobiome” of healthy individuals, and provides the basis for a detailed characterization of the oral mycobiome in health and disease.     

Natural environments,ancestral diets,and microbial ecology: is there a modern “paleo-deficit disorder”? Part I

Famed microbiologist René J. Dubos (1901–1982) was an early pioneer in the developmental origins of health and disease (DOHaD) construct. In the 1960s, he conducted groundbreaking experimental research concerning the ways in which early-life experience with nutrition, microbiota, stress, and other environmental variables could influence later-life health outcomes. He also wrote extensively on potential health consequences of a progressive loss of contact with natural environments (now referred to as green or blue space), arguing that Paleolithic experiences have created needs, particularly in the mental realm, that might not be met in the context of rapid global urbanization. He posited that humans would certainly adapt to modern urban landscapes and high technology, but there might be a toll to be paid in the form of higher psychological distress (symptoms of anxiety and depression) and diminished quality of life. In particular, there might be an erosion of humanness, exemplified by declines in altruism/empathy. Here in the first of a two-part review, we examine contemporary research related to natural environments and question to what extent Dubos might have been correct in some of his 50-year-old assertions.

“Human beings can almost certainly survive and multiply in the polluted cage of technological civilization, but we may sacrifice much of our humanness in adapting to such conditions…The maintenance of biological and mental health requires that technological societies provide in some form the biological freedom enjoyed by our Paleolithic ancestors”.Dr René Dubos, Invited Editorial, Life Magazine, 1970 [1].

     

A Randomized Controlled Trial to Test the Effectiveness of an Immersive 3D Video Game for Anxiety Prevention among Adolescents

Adolescent anxiety is debilitating, the most frequently diagnosed adolescent mental health problem, and leads to substantial long-term problems. A randomized controlled trial (n = 138) was conducted to test the effectiveness of a biofeedback video game (Dojo) for adolescents with elevated levels of anxiety. Adolescents (11–15 years old) were randomly assigned to play Dojo or a control game (Rayman 2: The Great Escape). Initial screening for anxiety was done on 1,347 adolescents in five high schools; only adolescents who scored above the “at-risk” cut-off on the Spence Children Anxiety Survey were eligible. Adolescents’ anxiety levels were assessed at pre-test, post-test, and at three month follow-up to examine the extent to which playing Dojo decreased adolescents’ anxiety. The present study revealed equal improvements in anxiety symptoms in both conditions at follow-up and no differences between Dojo and the closely matched control game condition. Latent growth curve models did reveal a steeper decrease of personalized anxiety symptoms (not of total anxiety symptoms) in the Dojo condition compared to the control condition. Moderation analyses did not show any differences in outcomes between boys and girls nor did age differentiate outcomes. The present results are of importance for prevention science, as this was the first full-scale randomized controlled trial testing indicated prevention effects of a video game aimed at reducing anxiety. Future research should carefully consider the choice of control condition and outcome measurements, address the potentially high impact of participants’ expectations, and take critical design issues into consideration, such as individual- versus group-based intervention and contamination issues.