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How to deal with regression to the mean in intervention studies

Cancer-related fatigue is common in patients with advanced lung cancer, persistently interfering with their health-related quality of life. Acceptance and Commitment Therapy (ACT) may effectively reduce fatigue interference and improve health-related quality of life in the advanced lung cancer population. This study aimed to evaluate the effects of an ACT-based intervention on fatigue interference and health-related quality of life in patients with advanced lung cancer.

An assessor-blinded, two-arm randomised controlled trial with 160 patients with advanced lung cancer was conducted. Participants were randomly allocated into either a four-week ACT-based intervention group (n = 80) or usual care control group (n = 80). The intervention consisted of a face-to-face session and three video-conferencing-based sessions and was delivered on an individual basis. The primary outcomes were fatigue interference and health-related quality of life. The secondary outcomes included cancer-related fatigue, depression and anxiety, cancer-specific distress, and activity level. Changes in psychological flexibility (PF), experiential avoidance, and cognitive fusion were also evaluated. Outcomes were measured at baselines (T0), one-week post-intervention (T1), and 3-month follow-up (T2). The intervention effects were assessed using generalised estimating equation models.

Compared with the control group, the intervention group demonstrated significant improvements in fatigue interference (T1: β = −0.50, p < 0.001; T2: β = −0.16, p = 0.007), health-related quality of life (T1: β = 16.01, p < 0.001; T2: β = 11.21, p < 0.001), depression (T1: β = −0.32, p < 0.001) and anxiety (T1: β = −0.20, p < 0.001), cancer-specific distress (T1: β = −7.37, p < 0.001; T2: β = −8.00, p < 0.001), activity level (intensity, T1: β = 3.24, p = 0.004; T2: β = 2.61, p = 0.020; frequency, T1: β = 2.44, p < 0.001; T2: β = 1.96, p < 0.001; duration, T1: β = 1.36, p < 0.001), PF (T1: β = 5.54, p < 0.001; T2: β = 8.63, p < 0.001), experiential avoidance (T1: β = −7.70, p < 0.001; T2: β = −10.07, p < 0.001), and cognitive fusion (T2: β = −3.31, p = 0.007). The changes in experiential avoidance at one-week post-intervention mediated the effects of ACT on reducing cancer-specific distress (β = −7.40, p < 0.001; β = −3.68, 95%CI, −5.77 to −1.58) and promoting HRQoL (β = 11.15, p < 0.001; β = 5.49, 95%CI, 3.09 to 8.31) at three-month follow-up. The changes in PF at one-week post-intervention mediated the effect of ACT on HRQoL (β = 11.15, p < 0.001; β = 2.25, 95%CI, 0.66 to 4.19) at three-month follow-up.

ACT-based intervention can effectively reduce fatigue interference and improve health-related quality of life in patients with advanced lung cancer. The intervention can be integrated into palliative care within the cancer system to contribute to the well-being of patients with advanced cancer.

Personalized interventions are regarded as a next-generation approach in almost all fields of biomedicine, such as clinical medicine, exercise, nutrition and pharmacology. At the same time, an increasing body of evidence indicates that redox processes regulate, at least in part, multiple aspects of human physiology and pathology. As a result, the idea of applying personalized redox treatments to improve their efficacy has gained popularity among researchers in recent years. The aim of the present primer-style review was to highlight some crucial yet underappreciated methodological, statistical, and interpretative concepts within the redox biology literature, while also providing a physiology-oriented perspective on personalized redox biology. The topics addressed are: (i) the critical issue of investigating the potential existence of inter-individual variability; (ii) the importance of distinguishing a genuine and consistent response of a subject from a chance finding; (iii) the challenge of accurately quantifying the effect of a redox treatment when dealing with ‘extreme’ groups due to mathematical coupling and regression to the mean; and (iv) research designs and analyses that have been implemented in other fields, and can be reframed and exploited in a redox biology context.

Substantial placebo response has been observed in trials assessing treatments in Raynaud's Phenomenon (RP), which makes any treatment effect difficult to detect. However, whether this response is due to a real placebo effect or to other nonspecific effects, such as regression towards the mean (RTM), has not been explored. Our objectives were to explore and quantify placebo response in RP, and to evaluate the magnitude of RTM contribution.

We combined trial-level and individual-level data from a series of n-of-1 trials and a network meta-analysis, respectively. Main outcomes were the daily frequency and the mean duration of RP attacks, as well as the Raynaud's Condition Score (RCS). We estimated the placebo response by the mean difference between the placebo period (or arm) and the baseline. RTM was estimated by the relationship between placebo response and baseline, and with Galton squeeze plots. Finally, we simulated the effect of the threshold used for inclusion in clinical trials on RTM.

We observed a large and significant placebo response from both individual and trial data for RCS [-1.20 (-1.63, -0.77) and -0.65 (-0.89, -0.41)] and the daily frequency of RP [-0.61 (-0.85, -0.37) and -0.75 (-0.95, -0.54)]. Outcome at baseline was significantly associated with placebo response, suggesting the presence of RTM. The latter was confirmed on individual data, through Galton squeeze plots.

Placebo response is large in RP trials, and likely due to regression towards the mean rather than ‘true’ placebo effect. This should be carefully considered when designing future trials.

This work has been partially supported by MIAI @ Grenoble Alpes (ANR-19-P3IA-0003).

Despite high prevalence, child neglect has long been passed over in research. Serious long-term consequences call for effective intervention programs. However, as a result of the lack of research, there is a lack of effective interventions. In order to develop such intervention programs and to maximize the effectiveness of existing programs, it is necessary to examine what factors are related to the reduction of neglect and, subsequently, what change mechanisms their effectiveness is based on.

In this intervention study we investigated whether changes in parental mental health and parental stress after Multisystemic Therapy for Child Abuse and Neglect (MST-CAN), an effective evidence-based intervention program for child neglect, are related to changes in child neglect.

Study participants were 144 parent-child dyads participating in the MST-CAN program.

We analyzed changes from pre- to post-treatment in child neglect, parental mental health, and parental stress, and conducted a multiple regression analysis to examine whether changes in parental mental health and parental stress predict changes in child neglect.

Our results showed that child neglect, as well as parental stress, significantly decreased and parental mental health significantly improved during the program. While improvements in parental mental health were not related to the reduction of child neglect, a decrease in parental stress significantly predicted the reduction of child neglect.

These findings suggest that parental stress might be a promising target for evidence-based intervention programs to reduce the occurrence of child neglect. Implications and suggestions for further research are discussed.

To investigate the symptom network structure of major depressive disorder (MDD) with mixed features and implications for treatment.

In this post-hoc analysis of a previously reported randomized trial, patients meeting DSM-IV-TR criteria for MDD presenting with two or three manic symptoms (DSM-5 mixed features specifier) were randomized to 6 weeks of double-blind treatment with lurasidone 20–60 mg/d (N = 109) or placebo (N = 100). The network structure of symptoms at baseline and their treatment moderating effects were investigated.

Network analyses showed that both ``elevated mood'' (YMRS item 1) and ``increased motor activity-energy'' (YMRS item 2) were associated with ``sleep disturbance'' (“bridge" symptom) and the depressive symptom cluster. Presence of both “elevated mood” and “increased motor activity-energy” at baseline predicted significantly less improvement in MADRS and CGI-S score at week 6 with lurasidone (vs. placebo) compared to patients without these manic symptoms at baseline. The network model also showed “rapid/pressured speech” (YMRS item 6) at baseline predicted improvement in both manic and depressive symptoms with lurasidone vs. placebo treatment.

This was a post-hoc analysis where findings need to be confirmed by prospective controlled studies.

This post-hoc analysis describes the symptom network structure of MDD with mixed features in a patient sample at study baseline. Specific manic symptoms were found to be linked to sleep disturbance (characterized as a “bridge” symptom), which in turn linked the manic and depressive symptom clusters. The presence (vs. absence) of the specific manic symptoms we identified moderated the antidepressant and antimanic effects of lurasidone in the treatment of MDD with mixed (subthreshold hypomanic) features.