Association and mediation analyses among multiple metal exposure, mineralocorticoid levels, and serum ion balance in residents of northwest China.

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou-Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose-response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.

The effect of acupuncture on exercise capacity in patients with COPD is mediated by improvements of dyspnea and leg fatigue: a causal mediation analysis using data from a randomized controlled trial.

BACKGROUND: Acupuncture is known to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD), but its mechanism remains unknown. Whether acupuncture improves exercise capacity in patients with COPD through alleviation of leg fatigue and dyspnea is examined by applying causal mediation analysis to previous trial data. METHODS: Sixty-two patients with COPD completed treatments with either real or placebo acupuncture once a week for 12 weeks. Walk distance measured using the 6-minute walk test and intensities of leg fatigue and dyspnea in the modified Borg scale were evaluated at baseline and after treatment. The intervention effect of acupuncture against the placebo acupuncture on two mediators, changes in leg fatigue and dyspnea, and whether they mediated improvements in walk distance, were analyzed. RESULTS: Linear regression analysis showed that the unstandardized regression coefficients [95% confidence interval (CI)] for the intervention effect by acupuncture were -4.9 (-5.8--4.0) in leg fatigue and -3.6 (-4.3--2.9) in dyspnea. Mediation analysis showed that when changes in leg fatigue were considered as a mediator, direct effect, indirect effect and proportion mediated were 47.1 m (95% CI, 4.6-85.1), 34.3 m (-2.1-82.1), and 42.1%, respectively, and when changes in dyspnea were considered as a mediator, they were 9.8 m (-32.9-49.9), 72.5 m (31.3-121.0), and 88.1%, respectively, and the effects of joint mediator were -5.8 m (-55.4-43.9), 88.9 m (32.7-148.5), and 107.0%, respectively. CONCLUSION: The improvement in exercise capacity by acupuncture is explained by changes in both leg fatigue and dyspnea.

The holistic nursing competence and transition shock of newly graduated nurses as the determinants of missed nursing care: The mediation analysis.

AIMS AND OBJECTIVE: To investigate the determinants of missed nursing care and to analyse the mediating effect of holistic nursing competence on the relationship between transition shock and missed nursing care. BACKGROUND: Transition shock of newly graduated nurses is associated with missed nursing care. Previous studies have shown the determinants of missed nursing care among nurses, but little is known about the relationship between missed nursing care, transition shock and holistic nursing competence. DESIGN: Descriptive and correlational design. METHODS: The study was conducted among newly graduated nurses (n = 201) working in acute care hospitals for 1-12 months. The MISSCARE survey, Holistic Nursing Competence Scale and Nursing Transition Shock Scale were used for data collection, in addition to a sociodemographic question form. Data were analysed using Pearson correlation, multiple regression and mediation analyses. The study was reported following the STROBE checklist. RESULTS: The determinants of missed nursing care among newly graduated nurses were sex, unit type, rotating shift work, holding a certificate, holistic nursing competence and transition shock. All these variables explain 35% of the variance in missed nursing care. Holistic nursing competence directly mediated 51.7% of the relationship between transition shock and missed nursing care. CONCLUSIONS: Holistic nursing competence may decrease missed nursing care by reducing the effects of transition shock on newly graduated nurses. RELEVANCE TO CLINICAL PRACTICE: The study highlighted that newly graduated nurses are an important population regarding missed nursing care. The determinants of missed care should be considered in the nursing care delivery to prevent missed care by newly graduated nurses. Based on the study findings, some recommendations were made for nurse managers and faculty for the orientation program and undergraduate nursing education.

Mediation analysis of urinary metals and stroke risk by inflammatory markers.

BACKGROUND: The association between metals and stroke has been reported, but the mediating role of inflammation between metals and stroke remains unclear. METHODS: We included 9326 adults from the National Health and Nutrition Examination Survey in this study. Through least absolute selection and shrinkage operator (LASSO) regression, weighted quantile sum (WQS) regression, logistic regression, linear regression, restricted cubic spline analysis, and mediation analysis, we explored the association between metals and stroke, as well as the association between metals and inflammatory indicators, and further evaluated the mediating effect of inflammatory indicators on the association between selected metals and stroke risk. RESULTS: The results of the present study suggested positive associations between mixed metals, cadmium and uranium and stroke risk. There is a positive correlation and dose‒response relationship between cadmium and C-reactive protein (CRP). Moreover, CRP mediates 10.1% of the association between cadmium and stroke. CONCLUSIONS: At the epidemiological level, CRP mediates the association between cadmium and stroke risk, suggesting that inflammation may be a potential mechanism for metal-induced stroke.

Low mindfulness is related to poor sleep quality from middle adolescents to emerging adults: a process model involving resilience and emotional dysfunction.

OBJECTIVES: Transitions from middle adolescence into merging adulthood, a life stage between age 15-25, has a high prevalence of sleep problems. Mindfulness is a trait defined as being attentive to the present moment which positively relates to sleep quality. In this study, we aimed to investigate how resilience and emotional dysfunction may influence the relationship between trait mindfulness and sleep quality. METHODS: The Five Facet Mindfulness Questionnaire, Connor-Davidson Resilience Scale, Pittsburgh Sleep Quality Index and Depression Anxiety Stress Scales were used to measure the key variables through an online survey of 497 participants between middle adolescence and emerging adults (317 females, mean age 18.27 ± 0.76 years). A process model was built to investigate the mediating roles of resilience and emotional dysfunction in the impact of trait mindfulness on sleep quality, together with the relationships between their specific components. RESULTS: We found a positive association between mindfulness and sleep quality through resilience and through emotional dysfunction, and through the sequential pathway from resilience to emotional dysfunction. Of note, acting with awareness (mindfulness facet) showed significant indirect effects on sleep quality, mediated by resilience and emotional dysfunction. CONCLUSIONS: Our findings may unveil the underlying mechanisms of how low mindfulness induces poor sleep quality. The findings indicate that conceiving mindfulness as a multifaceted construct facilitates comprehension of its components, relationships with other variables, and underscores its potential clinical significance given its critical implications for mental health.

Associations among internalized and perceived stigma, state mindfulness, self-efficacy, and depression symptoms among men who have sex with men in China: A serial mediation model.

Previous research has demonstrated that stigma is strongly related to depressive symptoms among men who have sex with men (MSM). However, data are limited regarding the associations between stigma, state mindfulness, self-efficacy, and depression symptoms. The current study aimed to analyze state mindfulness and self-efficacy as possible mediators between internalized and perceived stigma and depression symptoms. A sample of 2610 Chinese MSM (Mage = 23.99, SD = 6.09, age range: 18-68 years) was recruited from an online survey platform and completed the HIV and Homosexuality Related Stigma Scale, Patient Health Questionnaire-9, the short version of Five Facet Mindfulness Questionnaire, and the Chinese General Self-Efficacy Scale. Results indicated that state mindfulness significantly mediated the linkage between internalized and perceived stigma and depressive symptoms, and self-efficacy significantly mediated the relation between state mindfulness and depression symptoms. Furthermore, internalized and perceived stigma were associated with depression symptoms through a serial mediation of state mindfulness and self-efficacy. This study highlights that state mindfulness and self-efficacy might play important roles in the psychological response of MSM to stigmatization and psychopathology symptoms.

Mediation Analysis to Untangle Opposing Associations of High-Dose Docosahexaenoic Acid With IQ and Bronchopulmonary Dysplasia in Children Born Preterm.

Importance: High-dose omega-3 docosahexaenoic acid (DHA) supplementation of children born at less than 29 weeks' gestation has been shown to improve IQ despite increasing the risk of bronchopulmonary dysplasia (BPD). Given that BPD is associated with poorer cognitive outcomes, it is unclear whether the increased risk of BPD with DHA supplementation is associated with decreased benefit to IQ. Objective: To investigate whether the increased risk of BPD with DHA supplementation was associated with diminished IQ benefit. Design, Setting, and Participants: This cohort study used data collected from a multicenter, blinded, randomized controlled trial of DHA supplementation in children born at less than 29 weeks' gestation. Participants were recruited from 2012 to 2015 and followed up until 5 years' corrected age. Data were analyzed from November 2022 to February 2023. Interventions: Enteral DHA emulsion (60 mg/kg/d, to match the estimated in-utero requirement) or a control emulsion from the first 3 days of enteral feeds until 36 weeks' postmenstrual age or discharge home. Main Outcomes and Measures: Physiological BPD was assessed at 36 weeks' postmenstrual age. IQ was assessed at 5 years' corrected age using the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition; children from the 5 highest-recruiting Australian hospitals were assessed. The total effect of DHA supplementation on IQ was divided into direct and indirect effects using mediation analysis, with BPD as the presumed mediating variable. Results: Among 656 surviving children from hospitals involved in IQ follow-up (mean [SD] gestational age at birth, 26.8 [1.4] weeks; 346 males [52.7%]), there were 323 children with DHA supplementation and 333 children in the control group. Mean IQ was 3.45 points (95% CI, 0.38 to 6.53 points) higher in the DHA group than the control group, despite an increase in the risk of BPD (160 children [49.7%] vs 143 children [42.8%] with BPD). The indirect effect of DHA on IQ via BPD was not statistically significant (-0.17 points; 95% CI, -0.62 to 0.13 points), with most of the effect of DHA on IQ occurring independently of BPD (direct effect = 3.62 points; 95% CI, 0.55 to 6.81 points). Conclusions and Relevance: This study found that associations of DHA with BPD and IQ were largely independent. This finding suggests that if clinicians supplement children born preterm with high-dose DHA, any resulting increase in BPD risk would not be associated with meaningful reductions in the IQ benefit.

Triazine herbicides exposure, natural immunoglobulin M antibodies, and fasting plasma glucose changes: Association and mediation analyses in general Chinese urban adults.

The effects of triazine herbicides on glucose metabolism remain unclear. In this study, we aimed to assess the associations between serum triazine herbicides and glycemia-related risk indicators in general adults, and to evaluate the mediating role of natural immunoglobulin M antibodies (IgM) in the above associations among uninfected participants. We measured the concentrations of atrazine, cyanazine, and IgM in serum, as well as fasting plasma glucose (FPG), and fasting plasma insulin in 4423 adult participants from the Wuhan-Zhuhai cohort baseline population, enrolled in 2011-2012. Generalized linear models were used to evaluate the associations of serum triazine herbicides with glycemia-related risk indicators, and mediation analyses were performed to evaluate the mediating role of serum IgM in the above associations. The median levels of serum atrazine and cyanazine were 0.0237 µg/L and 0.0786 µg/L, respectively. Our study found significant positive associations of serum atrazine, cyanazine, and Σtriazine with FPG levels, risk of impaired fasting glucose (IFG), abnormal glucose regulation (AGR), and type 2 diabetes (T2D). Additionally, serum cyanazine and Σtriazine were found to be significant positive associated with the homeostatic model assessment of insulin resistance (HOMA-IR) levels. Significant negative linear relationships were observed in associations of serum IgM with serum triazine herbicides, FPG, HOMA-IR levels, the prevalence of T2D, and AGR (P < 0.05). Furthermore, we observed a significant mediating role by IgM in the associations of serum triazine herbicides with FPG, HOMA-IR, and AGR, with the proportions ranging from 2.96% to 7.71%. To ensure the stability of our findings, we conducted sensitivity analyses in normoglycemic participants and found that the association of serum IgM with FPG and the mediating role by IgM remained stable. Our results suggest that triazine herbicides exposure is positively associated with abnormal glucose metabolism, and decreasing serum IgM may partly mediate these associations.

Back to basics: A mediation analysis approach to addressing the fundamental questions of integrated care evaluations.

Health systems around the world are aiming to improve the integration of health and social care services to deliver better care for patients. Existing evaluations have focused exclusively on the impact of care integration on health outcomes and found little effect. That suggests the need to take a step back and ask whether integrated care programmes actually lead to greater clinical integration of care and indeed whether greater integration is associated with improved health outcomes. We propose a mediation analysis approach to address these two fundamental questions when evaluating integrated care programmes. We illustrate our approach by re-examining the impact of an English integrated care program on clinical integration and assessing whether greater integration is causally associated with fewer admissions for ambulatory care sensitive conditions. We measure clinical integration using a concentration index of outpatient referrals at the general practice level. While we find that the scheme increased integration of primary and secondary care, clinical integration did not mediate a decrease in unplanned hospital admissions. Our analysis emphasizes the need to better understand the hypothesized causal impact of integration on health outcomes and demonstrates how mediation analysis can inform future evaluations and program design.

Gut microbiota-mediated associations of green tea and catechin intakes with glucose metabolism in individuals without type 2 diabetes mellitus: a four-season observational study with mediation analysis.

This four-season observational study aimed to examine the mediating role of the gut microbiota in the associations between green tea and catechin intakes and glucose metabolism in individuals without type 2 diabetes mellitus (T2DM). In each of the 4 seasons, 85 individuals without T2DM (56 male [65.9%]; mean [standard deviation] age: 43.3 [9.4] years) provided blood samples, stool samples, 3-day weighed dietary records, and green tea samples. Catechin intake was estimated by analyzing the tea samples. Linear mixed-effects model analysis showed that green tea intake was negatively associated with fasting blood glucose and insulin levels, even after considering the seasonal variations. Of the gut microbial species associated with green tea intake, the mediation analysis revealed that Phocaeicola vulgatus mediated the association between green tea intake and fasting blood glucose levels. These findings indicate that green tea can improve glucose metabolism by decreasing the abundance of P. vulgatus that is associated with elevated blood glucose levels in individuals without T2DM.

A unified mediation analysis framework for integrative cancer proteogenomics with clinical outcomes.

MOTIVATION: Multilevel molecular profiling of tumors and the integrative analysis with clinical outcomes have enabled a deeper characterization of cancer treatment. Mediation analysis has emerged as a promising statistical tool to identify and quantify the intermediate mechanisms by which a gene affects an outcome. However, existing methods lack a unified approach to handle various types of outcome variables, making them unsuitable for high-throughput molecular profiling data with highly interconnected variables. RESULTS: We develop a general mediation analysis framework for proteogenomic data that include multiple exposures, multivariate mediators on various scales of effects as appropriate for continuous, binary and survival outcomes. Our estimation method avoids imposing constraints on model parameters such as the rare disease assumption, while accommodating multiple exposures and high-dimensional mediators. We compare our approach to other methods in extensive simulation studies at a range of sample sizes, disease prevalence and number of false mediators. Using kidney renal clear cell carcinoma proteogenomic data, we identify genes that are mediated by proteins and the underlying mechanisms on various survival outcomes that capture short- and long-term disease-specific clinical characteristics. AVAILABILITY AND IMPLEMENTATION: Software is made available in an R package (https://github.com/longjp/mediateR). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The role of emotion regulation in the relationship between mindfulness and risk factors for disordered eating: A longitudinal mediation analysis.

OBJECTIVE: Evidence suggests mindfulness may reduce risk factors for disordered eating. However, mechanisms of change in this relationship are unclear. This longitudinal study tested whether emotion regulation mediates the prospective associations between mindfulness and two proximal risk factors for disordered eating: weight and shape concerns, and negative affect. METHOD: This study is a secondary analysis of data collected within an eating disorder prevention trial. Adolescent girls (N = 374, Mage  = 15.70, SD = 0.77) completed self-report measures of mindfulness, emotion regulation, weight and shape concerns, and negative affect at baseline, 2 months following baseline, and 7 months following baseline. Path analyses were computed to test hypothesized indirect effects using confidence intervals based on 5000 bootstrap samples. RESULTS: Higher baseline mindfulness predicted lower weight and shape concerns and negative affect at 7 months via a mediator of better emotion regulation at 2 months. This effect remained while controlling for earlier measurements of the mediator and outcome in the model of negative affect but not weight and shape concerns. DISCUSSION: Emotion regulation may be an important mechanism explaining how mindfulness influences negative affect. Efforts should be made to intervene on mindfulness and emotion regulation in prevention and early intervention programmes for eating disorders and other psychiatric conditions. PUBLIC SIGNIFICANCE: Research has shown that mindfulness can help to reduce some of the risk of developing an eating disorder. This study explored whether mindfulness reduces some of this risk by helping people to better manage their emotions. Understanding this process can help us to develop better mindfulness-based strategies to support people who are at risk of developing an eating disorder.

Spirituality, self-compassion, and anxiety among sexual minority men: a longitudinal mediation analysis.

BACKGROUND AND OBJECTIVE: Research related to anxiety among sexual minority men (SMM) typically focuses on risk factors. It has seldom examined factors that may be associated with lower levels of anxiety. This gap in the literature represents an opportunity to explore positive psychological factors that may be related to lower levels of anxiety among this group. Spirituality and self-compassion are two positive psychological factors that have been associated with reduced anxiety in general samples but have been understudied among SMM. This study aimed to determine the longitudinal associations between spirituality, self-compassion, and anxiety. DESIGN AND METHODS: Guided by an Afrocentric psychological framework, we conducted a secondary quantitative analysis with data from a racially and ethnically diverse sample of 697 U.S. SMM. RESULTS: Utilizing Hayes PROCESS Macro Model 4, we found that spirituality at baseline was positively associated with self-compassion at baseline, which in turn was inversely associated with anxiety at 12-month follow-up. CONCLUSIONS: Overall, our findings provide evidence that spirituality and self-compassion are two positive psychological factors that are inversely associated with anxiety among SMM.

Mechanisms of improvement in generalized anxiety disorder: A mediation and moderated mediation analysis from a randomized controlled trial.

BACKGROUND: Generalized anxiety disorder (GAD) is associated with the lowest treatment response rate among all anxiety disorders. Understanding mechanisms of improvement may help to develop more effective and personalized treatments. AIM: The objective of the study was to investigate different improvement mechanisms in the treatment of individuals diagnosed with GAD. DESIGN: We reported data from a randomized controlled trial that evaluated three different GAD treatments (mindfulness-based intervention, BMT; fluoxetine, FLX; and an active comparison group, QoL) for 8 weeks. METHOD: Mediation analyses were performed evaluating the association between worry symptoms at baseline and anxiety scoring at the endpoint, considering self-compassion or mindfulness or its dimensions at mid-treatment as mediators for the whole sample (assessing GAD improvement mechanism) and the different interventions as moderators. RESULTS: Contrary to mindfulness state scoring (C = .06; 95% CI = -.05 to .20), self-compassion (C = .11; 95% CI = .01 to .28) and non-judgement of inner experience (C = .10; 95% CI = .004 to .21) mediated the association between worry symptoms at baseline and anxiety at the endpoint. When comparing BMT to FLX, the intervention modality did not moderate these associations. CONCLUSION: Self-compassion and non-judgement of inner experience seem to be essential targets in GAD treatment, contrary to the mindfulness state itself. Although no difference was found considering the intervention modality, future research may assess how to boost these dimensions in specific treatments for GAD.

Association Between Care Fragmentation and Total Spending After Durable Left Ventricular Device Implant: A Mediation Analysis of Health Care-Associated Infections Within a National Medicare-Society of Thoracic Surgeons Intermacs Linked Dataset.

BACKGROUND: Care fragmentation is associated with higher rates of infection after durable left ventricular assist device (LVAD) implant. Less is known about the relationship between care fragmentation and total spending, and whether this relationship is mediated by infections. METHODS: Total payments were captured from admission to 180 days post-discharge. Drawing on network theory, a measure of care fragmentation was developed based on the number of shared patients among providers (ie, anesthesiologists, cardiac surgeons, cardiologists, critical care specialists, nurse practitioners, physician assistants) caring for 4,987 Medicare beneficiaries undergoing LVAD implantation between July 2009 - April 2017. Care fragmentation was measured using average path length, which describes how efficiently information flows among network members; longer path length indicates greater fragmentation. Terciles based on the level of care fragmentation and multivariable regression were used to analyze the relationship between care fragmentation and LVAD payments and mediation analysis was used to evaluate the role of post-implant infections. RESULTS: The patient cohort was 81% male, 73% white, 11% Intermacs Profile 1 with mean (SD) age of 63.1 years (11.1). The mean (SD) level of care fragmentation in provider networks was 1.7 (0.2) and mean (SD) payment from admission to 180 days post-discharge was $246,905 ($109,872). Mean (SD) total payments at the lower, middle, and upper terciles of care fragmentation were $250,135 ($111,924), $243,288 ($109,376), and $247,290 ($108,241), respectively. In mediation analysis, the indirect effect of care fragmentation on total payments, through infections, was positive and statistically significant (ß=16032.5, p=0.008). CONCLUSIONS: Greater care fragmentation in the delivery of care surrounding durable LVAD implantation is associated with a higher incidence of infections, and consequently, higher payments for Medicare beneficiaries. Interventions to reduce care fragmentation may reduce the incidence of infections and in turn enhance the value of care for patients undergoing durable LVAD implantation.

Relationship between Different Dimensions of Workplace Spirituality and Psychological Well-Being: Measuring Mediation Analysis through Conditional Process Modeling.

The present study aims to identify the relationship between workplace spirituality, compassion, relationship with others at work, spiritual orientation, organizational value and alignment of personal values, and psychological well-being among universities' teachers. Further, the mediating effect of job stress was also identified between workplace spirituality and psychological well-being. Similarly, the mediation of environmental mastery between organizational values and alignment of personal values and psychological well-being was examined. Finally, we examined the mediation of personal growth between spiritual orientation and psychological well-being. The data were collected through a structured and adapted five-point Likert scale using a purposive sampling technique, with a total sample of 873 male and female university teachers working in the private and government universities. We employed structural equation modeling to check the relationship among the considered variables for analysis purposes. The results show a strong positive relationship between the independent and dependent variables. The findings further demonstrated that the mediation analysis confirms that job stress mediates the relationship between workplace spirituality and psychological well-being, and environmental mastery mediates between organizational values and alignment of personal values and psychological well-being. Finally, personal growth mediates between spiritual orientation and psychological well-being. To maintain the excellent quality of education, educational institutes need to identify and imply the practice of workplace spirituality that will help to reduce job stress and improve the psychological well-being of universities' teachers, thus resulting in better educational output.

Mediational Analysis of Yoga's Effect on Chronic Low-Back Pain in Veterans: What Factors Really Matter?

Considerable evidence supports yoga as a treatment for chronic low-back pain (CLBP), yet more research is needed on the mechanisms of yoga. Yoga may be particularly helpful for military veteran populations, where there is a high prevalence of CLBP due to intensive training requirements. Our objective was to examine possible mechanisms by which yoga reduced disability in a clinical trial of yoga for veterans with CLBP. Using data from a prior randomized controlled trial, we used mediation analysis to examine factors that may mediate or influence the effects of yoga on disability over time. The 12-week yoga intervention study measured outcomes at baseline, 6 weeks, 12 weeks, and 6 months. Fatigue and pain were the variables that met all statistical criteria for mediation of the effect of yoga on disability. The total effect of yoga on disability was significant (ß = -2.28; 95% CI -3.93 to -0.64), and this consisted of a direct effect of yoga (ß = -1.40; 95% CI -3.02 to 0.25) and a statistically significant indirect effect (ß = -0.88, 95% CI -1.91 to -0.15) that was mediated by pain and fatigue. The indirect effect accounted for 38% of yoga's effect on back-pain disability. Fatigue and pain were not significant as individual mediators. The other mediators-self-efficacy, spinal range of motion, grip strength, core strength, and balance-did not meet published criteria for mediation. Our results suggest that in veterans with CLBP, yoga may reduce pain and fatigue and contribute to reductions in disability. Although pain may be an expected precursor of disability, the finding that fatigue mediates the relationship between a mind-body intervention like yoga and disability appears novel. Fatigue should be measured more widely in yoga research and considered when designing interventions for specific populations such as military veterans with chronic pain.

Do Physical Therapy and Yoga Improve Pain and Disability through Psychological Mechanisms? A Causal Mediation Analysis of Adults with Chronic Low Back Pain.

OBJECTIVE: To investigate whether indirect effects via psychological mechanisms explain the effects of physical therapy (PT) or yoga versus education on back-related outcomes. DESIGN: Mediation analyses using data from a randomized controlled trial of PT, yoga, and education interventions for chronic low back pain. METHODS: Primary outcomes were changes in back-related pain on the 11-point numeric rating scale and disability on the modified 23-point Roland-Morris Disability Questionnaire, measured at 52 weeks after randomization. Hypothesized mediators were 12-week changes in pain self-efficacy, fear-avoidance beliefs, depression, anxiety, perceived stress, and sleep quality. We used causal mediation analysis to estimate the total effect, direct effect, indirect effect, and proportion mediated. RESULTS: We analyzed data from 230 adults (mean age = 46.2 years, 69.6% female, 79.6% non-White). In the PT-versus-education model, when the mediator was perceived stress, the total effect on disability was 2.6 points (95% confidence interval [CI]: 0.3, 4.9) and decomposed into a direct effect of 1.7 points (95% CI: -0.4, 3.8) and an indirect effect 0.9 points (95% CI: 0.1, 2.0; proportion mediated, 34%). No other psychological construct was a significant mediator. CONCLUSION: Improvements in perceived stress mediated improvements in disability after PT treatment compared to education. Other psychological outcomes did not mediate the effect of yoga or PT on pain or disability outcomes compared to education. J Orthop Sports Phys Ther 2022;52(7):470-483. Epub: 18 May 2022. doi:10.2519/jospt.2022.10813.

Mindful awareness as a mechanism of change for natural childbirth in pregnant women with high fear of childbirth: a randomised controlled trial.

BACKGROUND: Mindfulness-Based Childbirth and Parenting (MBCP) is effective in increasing natural childbirth in pregnant women with high fear of childbirth (FOC) as compared to enhanced care as usual (ECAU). We aimed to examine through which pathway of action MBCP reaches this effect, based on a model of approaching or avoiding the challenges related to childbirth. METHODS: One hundred eleven pregnant women with high FOC were measured pre- and post-intervention on FOC (emotion pathway), catastrophic beliefs about labour pain (cognition pathway) and mindful awareness (attention pathway). A multiple mediation model was used to examine through which pathway the mechanism of change operated in relation to approach (i.e., natural childbirth) versus avoidance (i.e., self-requested caesarean section). RESULTS: It was found that greater mindful awareness (18% R2 = 0.18, F[1107] = 22.77, p < 0.0001) was the only significant mechanism of change operating through the attentional pathway leading to natural childbirth. More specifically, nonreactivity to inner experience (a facet of mindful awareness) showed to be the strongest mechanism of change. More extensive meditation practice was positively associated with natural childbirth; however, the number of completed MBCP sessions was not associated with the outcome. CONCLUSIONS: An increase in mindful awareness was the strongest mechanism of change for better adaptation to the challenges of childbirth. Decreases in neither FOC nor catastrophic beliefs about labour pain were identified as mechanisms of change. Additionally, the more one meditated, the more one was inclined towards a natural childbirth. MBCP enhances adaptation to the challenges of childbirth and less use of obstetric interventions in the presence of high FOC. TRIAL REGISTRATION: The Netherlands Trial Register (NTR; 4302 ).

How does the Untire app alleviate cancer-related fatigue? A longitudinal mediation analysis.

OBJECTIVE: A waiting-list randomized controlled trial supported the effectiveness of the multimodal Untire app in reducing cancer-related fatigue (CRF) in cancer patients and survivors. However, little is known about the causal mechanisms of different app components through which the intervention effect was achieved. We aim to examine whether specifically targeted factors (i.e., fatigue catastrophizing, depression, mindfulness, sleep, and physical activity) mediated the intervention effects of the Untire app on fatigue outcomes. METHODS: Seven hundred ninety-nine persons with CRF were randomized (2:1) into intervention (n = 519) and waiting-list control (n = 280) groups. Self-report data on the primary outcome fatigue severity and interference and the abovementioned potential mediators were collected at baseline and 12 weeks. Participants who completed the 12-week assessment were included in the analyses (intervention = 159; control = 176). We performed longitudinal multi-categorical multiple mediation analysis using PROCESS macro to examine whether the potential mediators explained the overall intervention effects. RESULTS: Improvements in fatigue catastrophizing (bootstrap 95% CI (-0.110; -0.011)), depression (bootstrap 95% CI (-0.082; -0.004)), and mindfulness (bootstrap 95% CI (-0.082; -0.002)), significantly mediated the intervention effect on fatigue severity, whereas sleep quality (bootstrap 95% CI (-0.081; 0.009)), sleep disturbance (bootstrap 95% CI (-0.038; 0.029)), and physical activity (bootstrap 95% CI (-0.068; 0.000)) did not. Similar associations were found for fatigue interference. CONCLUSIONS: Untire app access reduces fatigue severity and interference mainly by decreasing fatigue catastrophizing, depression, and by increasing mindfulness. Supporting these psychological mechanisms is crucial for reducing fatigue among cancer patients and survivors.