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Working memory training has been shown to improve performance on untrained working memory tasks in typically developing children, at least when compared to non-adaptive training; however, there is little evidence that it improves academic outcomes. The lack of transfer to academic outcomes may be because children are only learning skills and strategies in a very narrow context, which they are unable to apply to other tasks. Metacognitive strategy interventions, which promote metacognitive awareness and teach children general strategies that can be used on a variety of tasks, may be a crucial missing link in this regard. In this double-blind randomized controlled trial, 95 typically developing children aged 9-14 years were allocated to three cognitive training programmes that were conducted daily after-school. One group received Cogmed working memory training, another group received concurrent Cogmed and metacognitive strategy training, and the control group received adaptive visual search training, which better controls for expectancy and motivation than non-adaptive training. Children were assessed on four working memory tasks, reading comprehension, and mathematical reasoning before, immediately after, and 3 months after training. Working memory training improved working memory and mathematical reasoning relative to the control group. The improvements in working memory were maintained 3 months later, and these were significantly greater for the group that received metacognitive strategy training, compared to working memory training alone. Working memory training is a potentially effective educational intervention when provided in addition to school; however, future research will need to investigate ways to maintain academic improvements long term and to optimize metacognitive strategy training to promote far-transfer. A video abstract of this article can be viewed at https://youtu.be/-7MML48ZFgw more...

This randomized clinical trial evaluates which specific components of internet-delivered cognitive behavioral therapy are active ingredients that reduce symptoms among patients with depression. Key Points: Question: Which specific components within internet-delivered cognitive behavioral therapy (CBT) for depression are active ingredients that reduce symptoms? Findings: In this randomized optimization trial that included 767 adults with depression, 6 treatment components (activity scheduling, thought challenging, relaxation, concreteness training, functional analysis, and self-compassion training) did not show a significant main effect on depression. However, the presence of the absorption component outperformed its absence in reducing depression at 6-month follow-up. Meaning: The findings suggest that the majority of treatment benefit from internet-delivered CBT is likely to accrue from factors common to all CBT components and/or from generic factors common to all therapies, with the possible exception of absorption. Importance: There is limited understanding of how complex evidence-based psychological interventions such as cognitive behavioral therapy (CBT) for depression work. Identifying active ingredients may help to make therapy more potent, brief, and scalable. Objective: To test the individual main effects and interactions of 7 treatment components within internet-delivered CBT for depression to investigate its active ingredients. Design, Setting, and Participants: This randomized optimization trial using a 32-condition, balanced, fractional factorial optimization experiment (IMPROVE-2) recruited adults with depression (Patient Health Questionnaire−9 [PHQ-9] score ≥10) from internet advertising and the UK National Health Service Improving Access to Psychological Therapies service. Participants were randomized from July 7, 2015, to March 29, 2017, with follow-up for 6 months after treatment until December 29, 2017. Data were analyzed from July 2018 to April 2023. Interventions: Participants were randomized with equal probability to 7 experimental factors within the internet CBT platform, each reflecting the presence vs absence of specific treatment components (activity scheduling, functional analysis, thought challenging, relaxation, concreteness training, absorption, and self-compassion training). Main Outcomes and Measures: The primary outcome was depression symptoms (PHQ-9 score). Secondary outcomes include anxiety symptoms and work, home, and social functioning. Results: Among 767 participants (mean age [SD] age, 38.5 [11.62] years; range, 18-76 years; 635 women [82.8%]), 506 (66%) completed the 6-month posttreatment follow-up. On average, participants receiving internet-delivered CBT had reduced depression (pre-to-posttreatment difference in PHQ-9 score, −7.79 [90% CI, −8.21 to −7.37]; 6-month follow-up difference in PHQ-9 score, −8.63 [90% CI, −9.04 to −8.22]). A baseline score–adjusted analysis of covariance model using effect-coded intervention variables (−1 or +1) found no main effect on depression symptoms for the presence vs absence of activity scheduling, functional analysis, thought challenging, relaxation, concreteness training, or self-compassion training (posttreatment: largest difference in PHQ-9 score [functional analysis], −0.09 [90% CI, −0.56 to 0.39]; 6-month follow-up: largest difference in PHQ-9 score [relaxation], −0.18 [90% CI, −0.61 to 0.25]). Only absorption training had a significant main effect on depressive symptoms at 6-month follow-up (posttreatment difference in PHQ-9 score, 0.21 [90% CI, −0.27 to 0.68]; 6-month follow-up difference in PHQ-9 score, −0.54, [90% CI, −0.97 to −0.11]). Conclusions and Relevance: In this randomized optimization trial, all components of internet-delivered CBT except absorption training did not significantly reduce depression symptoms relative to their absence despite an overall average reduction in symptoms. The findings suggest that treatment benefit from internet-delivered CBT probably accrues from spontaneous remission, factors common to all CBT components (eg, structure, making active plans), and nonspecific therapy factors (eg, positive expectancy), with the possible exception of absorption focused on enhancing direct contact with positive reinforcers. Trial Registration: isrctn.org Identifier: ISRCTN24117387 [ABSTRACT FROM AUTHOR] more...

Behavioural Activation (BA) is associated with a substantial evidence base for treatment of acute unipolar depression, and has promise as an easily disseminable psychological intervention for bipolar depression. Using a randomised multiple baseline case series design we examined the feasibility and acceptability of an adapted version of BA in a U.K. outpatient sample of 12 adults with acute bipolar depression. Participants were allocated at random to a 3–8 week wait period before being offered up to 20 sessions of BA. They completed outcome measures at intake, pre- and post-treatment and weekly symptom measures across the study period. Retention in therapy was high (11/12 participants completed the target minimum number of sessions), and all participants returning acceptability measures reported high levels of satisfaction with the intervention. No therapy-related serious adverse events were reported, nor were there exacerbations in manic symptoms that were judged to be a result of the intervention. The pattern of change on outcome measures is consistent with the potential for clinical benefit; six of the nine participants with a stable baseline showed clinically significant improvement on the primary outcome measure. The findings suggest adapted BA for bipolar depression is a feasible and acceptable approach that merits further investigation. [ABSTRACT FROM AUTHOR] more...

Objective: The aim of this study was to examine the effects of sudden gains and depression spikes in a randomized controlled trial of cognitive behavioral therapy (CBT) and behavioral activation (BA) for depression (COBRA trial). Method: This is a secondary analysis of 300 adults with major depressive disorder (MDD) who received CBT (n = 156) or BA (n = 144) (Richards et al., 2016). The Patient Health Questionnaire (PHQ-9) and Structured Clinical Interview Schedule (SCID) were used to measure depression symptoms at 6-, 12-, and 18-month follow-up. Results: One-hundred and ten (37%) individuals experienced sudden gains, and 77 (26%) experienced depression spikes. There were no differences in rates of gains or spikes between treatments. Individuals with sudden gains had lower PHQ-9 scores across follow-up and were less likely to meet SCID criteria than those without a sudden gain. Generalized estimating equation (GEE) models demonstrated that individuals who had a sudden gain and were in CBT had lower PHQ-9 scores at 6 and 18 months than those in BA. Conversely, individuals who had a depression spike and were in CBT had higher PHQ-9 scores across follow-up compared to those without a depression spike and also a greater chance of meeting SCID criteria for MDD at 18 months than those who received BA. Conclusions: The short- and long-term impact of discontinuous change varied by type of treatment package. Identifying strategies within treatment packages and client processes that are associated with gains and spikes may help to inform treatment planning and clinical decision-making. What is the public health significance of this article?: This study suggests that cognitive behavioral therapy (CBT) for major depressive disorder may help those who experience sudden gains to sustain this symptom improvement over the course of treatment and follow-up. The sustained behavioral focus in behavioral activation (BA) therapy may help individuals who experience a depression spike to apply concrete emotion regulation strategies that are also useful over the 18-month follow-up period. [ABSTRACT FROM AUTHOR] more...

Experiences of childhood trauma (abuse and neglect) are disproportionately higher in those with opioid use disorder (OUD). Childhood trauma may affect the reinforcing and rewarding properties of opioid drugs and responses to pain, potentially via developmental changes to the endogenous opioid system. This has been supported by preclinical research, yet this has not been investigated in non‐addicted humans. Physically healthy participants with either a history of severe childhood trauma or no previous history of childhood trauma attended two sessions where they received either an intramuscular active dose of morphine (0.15 mg/kg) or a very low dose control (0.01 mg/kg) in a randomised, double‐blind crossover design. Sessions were held 1 week apart. Participants' physical pain threshold and tolerance were measured pre‐ and post‐drug administration using the cold water pressor test, alongside acute subjective and behavioural responses over 2.5 h. The trauma group reported liking the effects of morphine, feeling more euphoric and wanting more of the drug over the session, as well as feeling less nauseous, dizzy, and dislike of the effects of morphine compared to the non‐trauma comparison group. Morphine increased pain threshold and tolerance, yet this did not differ between the groups. Childhood trauma may therefore sensitise individuals to the pleasurable and motivational effects of opioids and reduce sensitivity to the negative effects, providing compelling evidence for individual differences in opioid reward sensitivity. This may explain the link between childhood trauma and vulnerability to OUD, with consequent implications on interventions for OUD, the prescribing of opioids, and reducing stigmas surrounding OUD. [ABSTRACT FROM AUTHOR] more...

Aims: Reference laboratories advise immediate separation and freezing of samples for the assay of proinsulin, which limit its practicability for smaller centres. Following the demonstration that insulin and C-peptide are stable in EDTA at room temperature for at least 24hours, we undertook simple stability studies to establish whether the same might apply to proinsulin. Methods: Venous blood samples were drawn from six adult women, some fasting, some not, aliquoted and assayed immediately and after storage at either 4°C or ambient temperature for periods from 2h to 24h. Results: There was no significant variation or difference with storage time or storage condition in either individual or group analysis. Conclusion: Proinsulin appears to be stable at room temperature in EDTA for at least 24h. Immediate separation and storage on ice of samples for proinsulin assay is not necessary, which will simplify sample transport, particularly for multicentre trials. [ABSTRACT FROM AUTHOR] more...

Background: Depression is a global health challenge. Although there are effective psychological and pharmaceutical interventions, our best treatments achieve remission rates less than 1/3 and limited sustained recovery. Underpinning this efficacy gap is limited understanding of how complex psychological interventions for depression work. Recent reviews have argued that the active ingredients of therapy need to be identified so that therapy can be made briefer, more potent, and to improve scalability. This in turn requires the use of rigorous study designs that test the presence or absence of individual therapeutic elements, rather than standard comparative randomised controlled trials. One such approach is the Multiphase Optimization Strategy, which uses efficient experimentation such as factorial designs to identify active factors in complex interventions. This approach has been successfully applied to behavioural health but not yet to mental health interventions. Methods/Design: A Phase III randomised, single-blind balanced fractional factorial trial, based in England and conducted on the internet, randomized at the level of the patient, will investigate the active ingredients of internet cognitive-behavioural therapy (CBT) for depression. Adults with depression (operationalized as PHQ-9 score ≥ 10), recruited directly from the internet and from an UK National Health Service Improving Access to Psychological Therapies service, will be randomized across seven experimental factors, each reflecting the presence versus absence of specific treatment components (activity scheduling, functional analysis, thought challenging, relaxation, concreteness training, absorption, self-compassion training) using a 32-condition balanced fractional factorial design (2IV7-2). The primary outcome is symptoms of depression (PHQ-9) at 12 weeks. Secondary outcomes include symptoms of anxiety and process measures related to hypothesized mechanisms. Discussion: Better understanding of the active ingredients of efficacious therapies, such as CBT, is necessary in order to improve and further disseminate these interventions. This study is the first application of a component selection experiment to psychological interventions in depression and will enable us to determine the main effect of each treatment component and its relative efficacy, and cast light on underlying mechanisms, so that we can systematically enhance internet CBT. [ABSTRACT FROM AUTHOR] more...

Background: Tibial stress fractures (TSFs) cause a significant burden to Royal Marines recruits. No prospective running gait analyses have previously been performed in military settings.Aim: We aimed to identify biomechanical gait factors and anthropometric variables associated with increased risk of TSF.Methods: 1065 Royal Marines recruits were assessed in week 2 of training. Bilateral plantar pressure and three-dimensional lower limb kinematics were obtained for barefoot running at 3.6 m/s, providing dynamic arch index, peak heel pressure and lower limb joint angles. Age, bimalleolar breadth, calf girth, passive hip internal/external range of motion and body mass index (BMI) were also recorded. 10 recruits who sustained a TSF during training were compared with 120 recruits who completed training injury-free using a binary logistic regression model to identify injury risk factors.Results: 4 variables significantly (p<0.05) predicted increased risk of TSF (ORs and 95% CI): smaller bimalleolar width (0.73, 0.58 to 0.93), lower BMI (0.56, 0.33 to 0.95), greater peak heel pressure (1.25, 1.07 to 1.46) and lower range of tibial rotation (0.78, 0.63 to 0.96).Summary: Reduced impact attenuation and ability to withstand load were implicated in tibial stress fracture risk. [ABSTRACT FROM AUTHOR] more...

A number of authors have identified multiple concurrent sexual partnerships by both men and women to lie at the root of the HIV/AIDS epidemic in sub-Saharan Africa. This study applies multilevel models to Demographic and Health Survey data collected during 2003–2008 in 20 sub-Saharan African countries to examine the influence of social and cultural context on involvement with multiple sexual partnerships in the region, above and beyond the effects of individual characteristics. The findings provide support for the ecological argument that health behaviours are shaped and determined by societal conditions, in addition to the effects of individual and household characteristics. Involvement with multiple sex partners is most prevalent in societies in which sexual norms are widely permissive and where polygyny is common. Individual autonomy is substantial and attitudes towards sexuality are more liberal among men and women who live in communities in which sexual norms are widely permissive. Men and women who are most likely to have multiple sex partners in the sub-Saharan region are those who initiated sexual activity earlier and those who have the individual attributes (e.g. young age, urban residence, education, media exposure and working for cash and away from home) that bring to them more rights and/or decision-making autonomy, but not necessarily more financial resources and economic security (mostly among women). On the other hand, involvement with multiple partners is determined by cultural norms (i.e. permissive sexual norms) and social change (i.e. mass education, expansion of cash employment). The findings suggest a number of opportunities for more effective policy and programmatic responses to curb the prevalence of multiple partnerships in sub-Saharan Africa. [ABSTRACT FROM PUBLISHER] more...

Background: Prevention of depression is a priority to reduce its global disease burden. Targeting specific risk factors, such as rumination, may improve prevention. Rumination-focused Cognitive Behavioral Therapy (RFCBT) was developed to specifically target depressive rumination.Objective: The primary objective of this study was to test whether guided Web-based RFCBT (i-RFCBT) would prevent the incidence of major depression relative to usual care in UK university students. The secondary objective was to test the feasibility and estimated effect sizes of unguided i-RFCBT.Methods: To address the primary objective, a phase III randomized controlled trial was designed and powered to compare high risk university students (N=235), selected with elevated worry/rumination, recruited via an open access website in response to circulars within universities and internet advertisements, randomized to receive either guided i-RFCBT (interactive Web-based RFCBT, supported by asynchronous written Web-based support from qualified therapists) or usual care control. To address the secondary objective, participants were also randomized to an adjunct arm of unguided (self-administered) i-RFCBT. The primary outcome was the onset of a major depressive episode over 15 months, assessed with structured diagnostic interviews at 3 (postintervention), 6, and 15 months post randomization, conducted by telephone, blind to the condition. Secondary outcomes of symptoms of depression and anxiety and levels of worry and rumination were self-assessed through questionnaires at baseline and the same follow-up intervals.Results: Participants were randomized to guided i-RFCBT (n=82), unguided i-RFCBT (n=76), or usual care (n=77). Guided i-RFCBT reduced the risk of depression by 34% relative to usual care (hazard ratio [HR] 0.66, 95% CI 0.35 to 1.25; P=.20). Participants with higher levels of baseline stress benefited most from the intervention (HR 0.43, 95% CI 0.21 to 0.87; P=.02). Significant improvements in rumination, worry, and depressive symptoms were found in the short-to-medium term. Of the 6 modules, guided participants completed a mean of 3.46 modules (SD 2.25), with 46% (38/82) being compliant (completing ≥4 modules). Similar effect sizes and compliance rates were found for unguided i-RFCBT.Conclusions: Guided i-RFCBT can reduce the onset of depression in high-risk young people reporting high levels of worry/rumination and stress. The feasibility study argues for formally testing unguided i-RFCBT for prevention: if the observed effect sizes are robustly replicated in a phase III trial, it has potential as a scalable prevention intervention.Trial Registration: ISRCTN Registry ISRCTN12683436; https://www.isrctn.com/ISRCTN12683436 (Archived by WebCite at http://www.webcitation.org/77fqycyBX).International Registered Report Identifier (irrid): RR2-10.1186/s13063-015-1128-9. [ABSTRACT FROM AUTHOR] more...