Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials

Objective Mindfulness-based interventions (MBIs) can reduce risk of depressive relapse for people with a history of recurrent depression who are currently well. However, the cognitive, affective and motivational features of depression and anxiety might render MBIs ineffective for people experiencing current symptoms. This paper presents a meta-analysis of randomised controlled trials (RCTs) of MBIs where participants met diagnostic criteria for a current episode of an anxiety or depressive disorder. Method Post-intervention between-group Hedges g effect sizes were calculated using a random effects model. Moderator analyses of primary diagnosis, intervention type and control condition were conducted and publication bias was assessed. Results Twelve studies met inclusion criteria (n = 578). There were significant post-intervention between-group benefits of MBIs relative to control conditions on primary symptom severity (Hedges g = −0.59, 95% CI = −0.12 to −1.06). Effects were demonstrated for depressive symptom severity (Hedges g = −0.73, 95% CI = −0.09 to −1.36), but not for anxiety symptom severity (Hedges g = −0.55, 95% CI = 0.09 to −1.18), for RCTs with an inactive control (Hedges g = −1.03, 95% CI = −0.40 to −1.66), but not where there was an active control (Hedges g = 0.03, 95% CI = 0.54 to −0.48) and effects were found for MBCT (Hedges g = −0.39, 95% CI = −0.15 to −0.63) but not for MBSR (Hedges g = −0.75, 95% CI = 0.31 to −1.81). Conclusions This is the first meta-analysis of RCTs of MBIs where all studies included only participants who were diagnosed with a current episode of a depressive or anxiety disorder. Effects of MBIs on primary symptom severity were found for people with a current depressive disorder and it is recommended that MBIs might be considered as an intervention for this population

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study

Background: Tyrosine kinase inhibitors have shown activity in osteosarcoma and might enhance the efficacy of chemotherapy. We aimed to determine the recommended phase 2 dose and antitumour activity of lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma. // Methods: This multicentre, open-label, multicohort, phase 1/2 trial was done at 17 hospitals in six countries. Eligible patients were aged 2–25 years, had relapsed or refractory osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Lansky play–performance score or Karnofsky performance score of 50% or higher, up to one previous VEGF or VEGF receptor-targeted therapy, and a life expectancy of at least 3 months. This study includes a combination dose-finding phase 1 part (cohort 3A) and a phase 2 combination expansion in patients with osteosarcoma (cohort 3B). Lenvatinib was administered orally at a starting dose of 11 mg/m2 per day, capped at 24 mg per day, and etoposide (100 mg/m2 per day) plus ifosfamide (3000 mg/m2 per day) were administered intravenously on days 1–3 of each 21-day cycle for a maximum of five cycles. Lenvatinib monotherapy continued after these five cycles until disease progression, toxic effects, or patient choice to discontinue. The phase 1 primary endpoint was to determine the recommended phase 2 dose by evaluating dose-limiting toxicity and the phase 2 primary endpoint was progression-free survival at 4 months. Progression-free survival was measured in the full analysis set, which included all patients enrolled for efficacy outcomes; safety was assessed in all patients who received any study drug. This study is registered with ClinicalTrials.gov, NCT02432274. // Findings: 30 patients were screened for enrolment into cohort 3A between May 9, 2016, and June 3, 2019, and 22 patients for enrolment into cohort 3B between Sept 13, 2018, and July 18, 2019. Eight patients from cohort 3A and two from cohort 3B were ineligible for enrolment in the study. In phase 1, dose-limiting toxicities were observed in three patients (one in the lenvatinib 11 mg/m2 combination group and two in the 14 mg/m2 combination group) and the recommended phase 2 dose was determined as lenvatinib 14 mg/m2 per day (with daily dose cap of 24 mg) and etoposide 100 mg/m2 per day plus ifosfamide 3000 mg/m2 per day administered intravenously on days 1–3 of each 21-day cycle for a maximum of five cycles. 35 patients from phase 1 (cohort 3A; n=15) and phase 2 (cohort 3B; n=20) were treated at the recommended phase 2 dose and their results were pooled. Progression-free survival at 4 months was 51% (95% CI 34–69) in 18 of 35 patients per the binomial estimate. The most common grade 3–4 treatment-emergent adverse events were neutropenia (27 [77%] of 35), thrombocytopenia (25 [71%]), anaemia (19 [54%]), and decreased white blood cell count (19 [54%]). 26 [74%] of 35 patients had serious treatment-emergent adverse events and no treatment-related deaths occurred. // Interpretation: Lenvatinib with etoposide plus ifosfamide shows promising antitumour activity with no new safety signals in patients with refractory and relapsed osteosarcoma. These findings warrant further investigation in an ongoing randomised phase 2 study (NCT04154189)

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

Glycogen Utilization during Running: Intensity, Sex, and Muscle-specific Responses.

PURPOSE: To quantify net glycogen utilisation in the vastus lateralis (VL) and gastrocnemius (G) of male (n=11) and female (n=10) recreationally active runners during three outdoor training sessions. METHODS: After 2 days standardisation of carbohydrate (CHO) intakes (6 g.kg body mass per day), glycogen was assessed before and after 1) a 10-mile road run (10-mile) at lactate threshold, 2) 8 x 800 m track intervals (8 x 800 m) at velocity at V[Combining Dot Above]O2max and 3) 3 x 10 minute track intervals (3 x 10 min) at lactate turnpoint. RESULTS: Resting glycogen concentration was lower in the G of females compared with males (P0.05). Net glycogen utilisation was greater in males than females in both VL (P=0.02) and G (P=0.07) during the 10-mile road run. With the exception of males during the 3 x 10 min protocol (P=0.28), greater absolute glycogen utilisation was observed in the G versus the VL muscle in both males and females and during all training protocols (all comparisons, P<0.05). CONCLUSION: Data demonstrate 1) prolonged steady state running necessitates a greater glycogen requirement than shorter but higher intensity track running sessions, 2) females display evidence of reduced resting muscle glycogen concentration and net muscle glycogen utilisation when compared with males and 3), net glycogen utilisation is higher in the gastrocnemius muscle compared with the vastus lateralis

Measuring perceived exercise capability and investigating its relationship with childhood obesity: a feasibility study.

BACKGROUND/OBJECTIVES: According to the COM-B ('Capability', 'Opportunity', 'Motivation' and 'Behaviour') model of behaviour, three factors are essential for behaviour to occur: capability, opportunity and motivation. Obese children are less likely to feel capable of exercising. The implementation of a new methodological approach to investigate the relationship between perceived exercise capability (PEC) and childhood obesity was conducted, which involved creating a new instrument, and demonstrating how it can be used to measure obesity intervention outcomes. SUBJECTS/METHODS: A questionnaire aiming to measure perceived exercise capability, opportunity and motivation was systematically constructed using the COM-B model and administered to 71 obese children (aged 9-17 years (12.24±0.2.01), body mass index (BMI) standard deviation scores (SDS) 2.80±0.660) at a weight-management camp in northern England. Scale validity and reliability was assessed. Relationships between PEC, as measured by the questionnaire, and BMI SDS were investigated for the children at the weight-management camp, and for 45 Spanish schoolchildren (aged 9-13 years, (10.52±1.23), BMI SDS 0.80±0.99). A pilot study, demonstrating how the questionnaire can be used to measure the effectiveness of an intervention aiming to bring about improved PEC for weight-management camp attendees, was conducted. No participants withdrew from these studies. RESULTS: The questionnaire domain (exercise capability, opportunity and motivation) composite scales were found to have adequate internal consistency (a=0.712-0.796) and construct validity (χ(2)/degrees of freedom=1.55, root mean square error of approximation=0.072, comparative fit index=0.92). Linear regression revealed that low PEC was associated with higher baseline BMI SDS for both UK (b=-0.289, P=0.010) and Spanish (b=-0.446, P=0.047) participants. Pilot study findings provide preliminary evidence for PEC improvements through intervention being achievable, and measurable using the questionnaire. CONCLUSIONS: Evidence is presented for reliability and validity of the questionnaire, and for feasibility of its use in the context of a childhood obesity intervention. Future research could investigate the link between PEC and childhood obesity further

Phylogenetic Patterns of Colonization and Extinction in Experimentally Assembled Plant Communities

Evolutionary history has provided insights into the assembly and functioning of plant communities, yet patterns of phylogenetic community structure have largely been based on non-dynamic observations of natural communities. We examined phylogenetic patterns of natural colonization, extinction and biomass production in experimentally assembled communities.We used plant community phylogenetic patterns two years after experimental diversity treatments (1, 2, 4, 8 or 32 species) were discontinued. We constructed a 5-gene molecular phylogeny and statistically compared relatedness of species that colonized or went extinct to remaining community members and patterns of aboveground productivity. Phylogenetic relatedness converged as species-poor plots were colonized and speciose plots experienced extinctions, but plots maintained more differences in composition than in phylogenetic diversity. Successful colonists tended to either be closely or distantly related to community residents. Extinctions did not exhibit any strong relatedness patterns. Finally, plots that increased in phylogenetic diversity also increased in community productivity, though this effect was inseparable from legume colonization, since these colonists tended to be phylogenetically distantly related.We found that successful non-legume colonists were typically found where close relatives already existed in the sown community; in contrast, successful legume colonists (on their own long branch in the phylogeny) resulted in plots that were colonized by distant relatives. While extinctions exhibited no pattern with respect to relatedness to sown plotmates, extinction plus colonization resulted in communities that converged to similar phylogenetic diversity values, while maintaining differences in species composition

A randomised controlled trial of a brief online mindfulness-based intervention in a non-clinical population: replication and extension

Building on previous research, this study compared the effects of two brief, online mindfulness-based interventions (MBIs; with and without formal meditation practice) and a no intervention control group in a non-clinical sample. One hundred and fifty-five university staff and students were randomly allocated to a 2-week, self-guided, online MBI with or without mindfulness meditation practice, or a wait list control. Measures of mindfulness, perceived stress, perseverative thinking and anxiety/depression symptoms within were administered before and after the intervention period. Intention to treat analysis identified significant differences between groups on change over time for all measured outcomes. Participation in the MBIs was associated with significant improvements in all measured domains (all ps < 0.05), with effect sizes in the small to medium range (0.25 to 0.37, 95% CIs 0.11 to 0.56). No significant changes on these measures were found for the control group. Change in perseverative thinking was found to mediate the relationship between condition and improvement on perceived stress and anxiety/ depression symptom outcomes. Contrary to our hypotheses, no differences between the intervention conditions were found. Limitations of the study included reliance on self-report data, a relatively high attrition rate and absence of a longer-term follow-up. This study provides evidence in support of the feasibility and effectiveness of brief, self-guided MBIs in a non-clinical population and suggests that reduced perseverative thinking may be a mechanism of change. Our findings provide preliminary evidence for the effectiveness of a mindfulness psychoeducation condition, without an invitation to formal mindfulness meditation practice. Further research is needed to confirm and better understand these results and to test the potential of such interventions