From Fetus to Eight: the CHILD Cohort Study.

The CHILD Cohort Study is an active multi-center longitudinal, prospective, population pregnancy cohort study following Canadian infants from fetal life until adulthood. We hypothesized that early life physical and psychosocial environments interact with biological factors (e.g. immunologic, genetic, physiologic, and metabolic) influencing burdensome non-communicable disease outcomes, including asthma and allergic disorders, growth and development, cardio-metabolic health, and neurodevelopmental outcomes that manifest during the life-course. Detailed clinical and physiologic phenotyping at strategic intervals was complemented by environmental sampling, actigraphy and global positioning system measures, biological sampling including gut, breastmilk and nasal microbiome, nutritional studies, genetics, and epigenetic profiling. Of 3,454 families recruited from 2008 to 2012, study retention was 96.0% at 1-year, 93.2% at 5-years and 90.7% at 8-years. Data collection during the SARS-2 COVID-19 pandemic was partially completed via virtual visits. A sub-cohort was implemented, capturing detailed information on the prevalence and predictors of SARS-CoV-2 infection and the health and psychosocial impact of the pandemic on Canadian families. The 13-year clinical assessment launched in 2022 will be completed in 2025. Ultimately, the CHILD Cohort Study provides a data science platform designed to enable a deep understanding of early life factors associated with the development of chronic non-communicable diseases and multimorbidity.

A guide to behavioural experiments in bipolar disorder.

Behavioural experiments are an important component of cognitive-behavioural therapy. However, there exists little up-to-date guidance on how to conduct these in people with a diagnosis of bipolar disorder. This paper provides recommendations on how to conduct behavioural experiments in this population. The aim is to upskill and empower clinicians to conduct behavioural experiments. The paper combines the expertise of senior clinicians working in the United Kingdom. The article starts by providing general advice on conducting behavioural experiments in people with bipolar disorder. It then offers specific examples of behavioural experiments targeting cognitions around the uncontrollability and danger of affective states, and related behavioural strategies, which have been implicated in the maintenance of bipolar mood swings. The article finishes by providing examples of behavioural experiments for non-mood related difficulties that commonly occur with bipolar experiences including perfectionistic thinking, need for approval, and intrusive memories. Behavioural experiments offer a useful therapeutic technique for instigating cognitive and behavioural change in bipolar disorder. Conducted sensitively and collaboratively, in line with people's recovery-focused goals, behavioural experiments can be used to overcome mood- and non-mood related difficulties.

Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial.

BACKGROUND: Depression is a common, debilitating, and costly disorder. Many patients request psychological therapy, but the best-evidenced therapy-cognitive behavioural therapy (CBT)-is complex and costly. A simpler therapy-behavioural activation (BA)-might be as effective and cheaper than is CBT. We aimed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression. METHODS: In this randomised, controlled, non-inferiority trial, we recruited adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder from primary care and psychological therapy services in Devon, Durham, and Leeds (UK). We excluded people who were receiving psychological therapy, were alcohol or drug dependent, were acutely suicidal or had attempted suicide in the previous 2 months, or were cognitively impaired, or who had bipolar disorder or psychosis or psychotic symptoms. We randomly assigned participants (1:1) remotely using computer-generated allocation (minimisation used; stratified by depression severity [Patient Health Questionnaire 9 (PHQ-9) score of <19 vs ≥19], antidepressant use, and recruitment site) to BA from junior mental health workers or CBT from psychological therapists. Randomisation done at the Peninsula Clinical Trials Unit was concealed from investigators. Treatment was given open label, but outcome assessors were masked. The primary outcome was depression symptoms according to the PHQ-9 at 12 months. We analysed all those who were randomly allocated and had complete data (modified intention to treat [mITT]) and also all those who were randomly allocated, had complete data, and received at least eight treatment sessions (per protocol [PP]). We analysed safety in the mITT population. The non-inferiority margin was 1·9 PHQ-9 points. This trial is registered with the ISCRTN registry, number ISRCTN27473954. FINDINGS: Between Sept 26, 2012, and April 3, 2014, we randomly allocated 221 (50%) participants to BA and 219 (50%) to CBT. 175 (79%) participants were assessable for the primary outcome in the mITT population in the BA group compared with 189 (86%) in the CBT group, whereas 135 (61%) were assessable in the PP population in the BA group compared with 151 (69%) in the CBT group. BA was non-inferior to CBT (mITT: CBT 8·4 PHQ-9 points [SD 7·5], BA 8·4 PHQ-9 points [7·0], mean difference 0·1 PHQ-9 points [95% CI -1·3 to 1·5], p=0·89; PP: CBT 7·9 PHQ-9 points [7·3]; BA 7·8 [6·5], mean difference 0·0 PHQ-9 points [-1·5 to 1·6], p=0·99). Two (1%) non-trial-related deaths (one [1%] multidrug toxicity in the BA group and one [1%] cancer in the CBT group) and 15 depression-related, but not treatment-related, serious adverse events (three in the BA group and 12 in the CBT group) occurred in three [2%] participants in the BA group (two [1%] patients who overdosed and one [1%] who self-harmed) and eight (4%) participants in the CBT group (seven [4%] who overdosed and one [1%] who self-harmed). INTERPRETATION: We found that BA, a simpler psychological treatment than CBT, can be delivered by junior mental health workers with less intensive and costly training, with no lesser effect than CBT. Effective psychological therapy for depression can be delivered without the need for costly and highly trained professionals. FUNDING: National Institute for Health Research.

Evaluating gulls as potential vehicles of Salmonella enterica serotype Newport (JJPX01.0061) contamination of tomatoes grown on the eastern shore of Virginia.

Salmonella enterica serovar Newport pattern JJPX01.0061 has been identified as causing several multistate outbreaks in the last 10 years, primarily due to contamination of tomatoes grown in Virginia. The goal of this study was to evaluate gulls as a potential vehicle of S. Newport pattern 61 contamination for tomatoes grown on the Eastern Shore of Virginia. Gull fecal samples were collected at four sites in eastern Virginia for 3 months (May to July) in 2012, resulting in 360 samples, among which Salmonella was isolated from 62 samples. Twenty-two serotypes and 26 pulsed-field gel electrophoresis DNA fingerprint patterns, including S. Newport pattern 61, were identified. All of the patterns that were isolated multiple times, with the exception of S. Newport patterns JJPX01.0030 and JJPX01.0061, were clustered in time and geographical location. These results strongly suggest that both patterns of S. Newport are endemic to sites on the Eastern Shore where gulls were sampled. This study provides additional information regarding the epidemiology of S. Newport pattern 61 in Virginia and how tomatoes sold interstate may become contaminated in the field.

Ultra-Brief Breath Counting (Mindfulness) Training Abolishes Negative Affect-Induced Alcohol Motivation in Hazardous Community Drinkers.

Objectives: Mindfulness therapy improves drinking outcomes arguably by attenuating negative mood-induced drinking, but this mechanism has not been demonstrated in hazardous community drinkers. To address this, three studies tested whether a key ingredient of mindfulness, breath counting, would attenuate the increase in motivation for alcohol produced by experimentally induced negative mood, in hazardous community drinkers. Method: In three studies, hazardous community drinkers were randomized to receive either a 6-min breath counting training or listen to a recited extract from a popular science book, before all participants received a negative mood induction. Motivation for alcohol was measured before and after listening to either the breath counting training or the control audio files, with a craving questionnaire in two online studies (n = 122 and n = 111), or an alcohol versus food picture choice task in a pub context in one in-person study (n = 62). Results: In Study 1, breath counting reduced alcohol craving. However, since the mood induction protocol did not increase craving, the effect of breath counting in reversing such increase could not be demonstrated. Online breath counting eliminated the increase in alcohol craving induced by negative mood (Study 2) and eliminated the stress-induced increase in alcohol picture choice in the pub environment (Study 3). Conclusions: Briefly trained breath counting attenuated negative mood-induced alcohol motivation in hazardous community drinkers. These results suggest that breath counting is a reliable and practical method for reducing the impact of negative emotional triggers on alcohol motivation. Preregistration: These studies are not preregistered.

Augmented Depression Therapy for young adults: A mixed methods randomised multiple baseline case series evaluation.

Augmented Depression Therapy (ADepT) is an individual psychotherapy for depression, which has been shown to be effective in the general adult population. A randomised multiple baseline case series evaluated the feasibility, acceptability, and effectiveness of ADepT in young adults (aged 20-24). Eleven depressed young adults were recruited from a UK university wellbeing service to receive ADepT during the COVID-19 pandemic, with outcomes evaluated relative to pre-specified continuation targets. All participants received a minimum adequate treatment dose (>60% target); 89% judged ADepT as acceptable and satisfactory and would recommend it to others (>60% target); only 9% showed reliable deterioration for depression or wellbeing (meeting <30% target); and there were no trial- or treatment-related serious adverse events. Qualitative interviews revealed most participants were satisfied with and experienced benefits from ADepT. At post-treatment, reliable improvement was shown by 33% of participants for depression and 67% of participants for wellbeing (not meeting target of both >60%), with medium effect size improvements for depression (g = 0.78) and large effect size improvement for wellbeing (g = 0.93; not meeting target of both >0.80). ADepT is feasible, acceptable, and safe in young adults but may require modification to maximise effectiveness. Further research outside of the COVID-19 pandemic is warranted.

Experiences of imagery-based treatment for anxiety in bipolar disorder: A qualitative study embedded within the image based emotion regulation feasibility randomised controlled trial.

OBJECTIVES: Intrusive mental imagery is associated with anxiety in bipolar disorder (BD) and presents a novel treatment target. Imagery-based treatments show promise in targeting anxiety and improving mood instability. This qualitative study explored experiences of receiving up to 12 sessions of a brief structured psychological intervention: Image-Based Emotion Regulation (IBER), which targets maladaptive mental imagery in the context of BD with an aim to modify the emotional impact of these images. DESIGN: A qualitative study embedded within the Image Based Emotion Regulation (IBER) feasibility randomised controlled trial. METHODS: Semi-structured interviews were conducted with 12 participants in the treatment arm of the trial who received IBER + treatment as usual. Data were analysed using thematic analysis. RESULTS: Despite some initial scepticism about imagery-focused treatment, all participants expressed broadly positive accounts of treatment experiences. High levels of engagement with imagery modification techniques, beneficial use of techniques post treatment and improvements in anxiety management and agency were described by some. Three sub-groups were identified: those who reported a powerful transformative impact of treatment; those who embedded some new techniques into their daily lives, and those who felt they had techniques to use when needed. No participants reported overall negative experiences of the IBER treatment. CONCLUSIONS: Findings from this study highlight the value for treatment recipients of modifying the underlying meanings associated with maladaptive imagery, and the personalised skills development to manage anxiety within bipolar disorders. Findings can inform treatment refinements and further trial-based evaluations.

Fatigue outcomes following COVID-19: a systematic review and meta-analysis.

OBJECTIVES: Fatigue is a pervasive clinical symptom in coronaviruses and may continue beyond the acute phase, lasting for several months or years. This systematic review and meta-analysis aimed to incorporate the current evidence for postinfection fatigue among survivors of SARS-CoV-2 and investigate associated factors. METHODS: Embase, PsyINFO, Medline, CINAHL, CDSR, Open Grey, BioRxiv and MedRxiv were systematically searched from January 2019 to December 2021. Eligible records included all study designs in English. Outcomes were fatigue or vitality in adults with a confirmed diagnosis of SARS-CoV-2 measured at >30 days post infection. Non-confirmed cases were excluded. JBI risk of bias was assessed by three reviewers. Random effects model was used for the pooled proportion with 95% CIs. A mixed effects meta-regression of 35 prospective articles calculated change in fatigue overtime. Subgroup analyses explored specific group characteristics of study methodology. Heterogeneity was assessed using Cochran's Q and I2 statistic. Egger's tests for publication bias. RESULTS: Database searches returned 14 262 records. Following deduplication and screening, 178 records were identified. 147 (n=48 466 participants) were included for the meta-analyses. Pooled prevalence was 41% (95% CI: 37% to 45%, k=147, I2=98%). Fatigue significantly reduced over time (-0.057, 95% CI: -107 to -0.008, k=35, I2=99.3%, p=0.05). A higher proportion of fatigue was found in studies using a valid scale (51%, 95% CI: 43% to 58%, k=36, I2=96.2%, p=0.004). No significant difference was found for fatigue by study design (p=0.272). Egger's test indicated publication bias for all analyses except valid scales. Quality assessments indicated 4% at low risk of bias, 78% at moderate risk and 18% at high risk. Frequently reported associations were female gender, age, physical functioning, breathlessness and psychological distress. CONCLUSION: This study revealed that a significant proportion of survivors experienced fatigue following SARS-CoV-2 and their fatigue reduced overtime. Non-modifiable factors and psychological morbidity may contribute to ongoing fatigue and impede recovery. PROSPERO REGISTRATION NUMBER: CRD42020201247.

Preliminary clinical and cost effectiveness of augmented depression therapy versus cognitive behavioural therapy for the treatment of anhedonic depression (ADepT): a single-centre, open-label, parallel-group, pilot, randomised, controlled trial.

Background: Anhedonia (reduced interest/pleasure) symptoms and wellbeing deficits are core to depression and predict a poor prognosis. Current depression psychotherapies fail to target these features adequately, contributing to sub-optimal outcomes. Augmented Depression Therapy (ADepT) has been developed to target anhedonia and wellbeing. We aimed to establish clinical and economic proof of concept for ADepT and to examine feasibility of a future definitive trial comparing ADepT to Cognitive Behavioural Therapy (CBT). Methods: In this single-centre, open-label, parallel-group, pilot randomised controlled trial, adults meeting diagnostic criteria for a current major depressive episode, scoring ≥10 on the Patient Health Questionnaire (PHQ-9) and exhibiting anhedonic features (PHQ-9 item 1 ≥ 2) were recruited primarily from high intensity Improving Access to Psychological Therapy (IAPT) service waiting lists in Devon, UK. Participants were randomised to receive 20 sessions of CBT or ADepT, using a mimimisation algorithm to balance depression severity and antidepressant use between groups. Treatment was delivered in an out-patient university-based specialist mood disorder clinic. Researcher-blinded assessments were completed at intake and six, 12, and 18 months. Co-primary outcomes were depression (PHQ-9) and wellbeing (Warwick Edinburgh Mental Wellbeing Scale) at 6 months. Primary clinical proof-of-concept analyses were intention to treat. Feasibility (including safety) and health economic analyses used complete case data. This trial is registered at the ISRCTN registry, ISRCTN85278228. Findings: Between 3/29/2017 and 7/31/2018, 82 individuals were recruited (102% of target sample) and 41 individuals were allocated to each arm. A minimum adequate treatment dose was completed by 36/41 (88%) of CBT and 35/41 (85%) of ADepT participants. There were two serious adverse events in each arm (primarily suicide attempts; none of which were judged to be trial- or treatment-related), with no other evidence of harms. Intake and six-month primary outcome data was available for 37/41 (90%) CBT participants and 32/41 (78%) ADepT participants. Between-group effects favoured ADepT over CBT for depression (meanΔ = -1.35, 95% CI = -3.70, 1.00, d = 0.23) and wellbeing (meanΔ = 2.64, 95% CI = -1.71, 6.99, d = 0.27). At 18 months, the advantage of ADepT over CBT was preserved and ADepT had a >80% probability of cost-effectiveness. Interpretation: These findings provide proof of concept for ADepT and warrant continuation to definitive trial. Funding: NIHR Career Development Fellowship.

The IBER study: a feasibility randomised controlled trial of imagery based emotion regulation for the treatment of anxiety in bipolar disorder.

BACKGROUND: Intrusive mental imagery is associated with anxiety and mood instability within bipolar disorder and therefore represents a novel treatment target. Imagery Based Emotion Regulation (IBER) is a brief structured psychological intervention developed to enable people to use the skills required to regulate the emotional impact of these images. METHODS: Participants aged 18 and over with a diagnosis of bipolar disorder and at least a mild level of anxiety were randomly assigned (1:1) to receive IBER plus treatment as usual (IBER + TAU) or treatment as usual alone (TAU). IBER was delivered in up to 12 sessions overs 16 weeks. Clinical and health economic data were collected at baseline, end of treatment and 16-weeks follow-up. Objectives were to inform the recruitment process, timeline and sample size estimate for a definitive trial and to refine trial procedures. We also explored the impact on participant outcomes of anxiety, depression, mania, and mood stability at 16-weeks and 32-weeks follow-up. RESULTS: Fifty-seven (28: IBER + TAU, 27: TAU) participants from two sites were randomised, with 50 being recruited within the first 12 months. Forty-seven (82%) participants provided outcome data at 16 and 32-weeks follow-up. Thirty-five participants engaged in daily mood monitoring at the 32-week follow-up stage. Retention in IBER treatment was high with 27 (96%) attending ≥ 7 sessions. No study participants experienced a serious adverse event. DISCUSSION: The feasibility criteria of recruitment, outcome completion, and intervention retention were broadly achieved, indicating that imagery-focused interventions for bipolar disorder are worthy of further investigation.

Off-pump injectable versus on-pump conventional tissue valves for pulmonary valve replacement: the injectable valve implantation randomised trial (INVITE).

OBJECTIVES: To assess the effectiveness of injectable tissue pulmonary valve compared with standard pulmonary valve in patients requiring pulmonary valve replacement surgery. DESIGN: A multicentre, single-blind, parallel two-group randomised controlled trial. Participants were blind to their allocation. Follow-up continued for 6 months. Randomised allocations were generated by a computer using block randomisation, stratified by centre. SETTING: Two National Health Service secondary care centres in the UK. PARTICIPANTS: People aged 12-80 years requiring pulmonary valve replacement. INTERVENTIONS: Participants were randomly allocated (1:1 ratio) to injectable pulmonary valve replacement (IPVR) without cardiopulmonary bypass (CPB) or standard pulmonary valve replacement (SPVR) with CPB. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was chest drainage volume over the first 24 hours after surgery. Secondary outcomes included in-hospital clinical outcomes; valve and heart function 6 months postsurgery and health-related quality of life 6 weeks and 6 months postsurgery. RESULTS: Nineteen participants agreed to take part. Eleven were allocated to IPVR and eight to SPVR. The trial was stopped before the target sample size of 60 participants was reached due to challenges in recruitment. The primary analysis includes all randomised participants; there were no withdrawals. Chest drain volume 24 hours after surgery was on average 277.6 mL lower with IPVR (IPVR mean 340.0 mL; SPVR mean 633.8 mL; mean difference, -277.6; 95% CI, -484.0 to -71.2; p=0.005). There were no statistically significant differences in time to readiness for extubation (p=0.476), time to fitness for discharge (p=0.577) and time to first discharge from the intensive care unit (p=0.209). Six participants with IPVR required CPB. Safety profiles and quality of life scores were similar. CONCLUSIONS: IPVR reduced chest drain volume despite >50% of participants requiring CPB. There was no evidence of any other benefit of IPVR. TRIAL REGISTRATION NUMBER: ISRCTN23538073.

Cohort profile: investigating SARS-CoV-2 infection and the health and psychosocial impact of the COVID-19 pandemic in the Canadian CHILD Cohort.

The coronavirus disease 2019 (COVID-19) pandemic has affected all Canadian families, with some impacted differently than others. Our study aims to: (1) determine the prevalence and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Canadian families, (2) identify predictors of infection susceptibility and severity of SARS-CoV-2, and (3) identify health and psychosocial impacts of the COVID-19 pandemic. This study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3,454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009 and 2012. During the pandemic, CHILD households were invited to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure and testing, vaccination status, physical and mental health, and pandemic-driven life changes; and (3) in-home biological sampling kits to collect blood and stool. In total, 1,462 households (5,378 participants) consented to the CHILD COVID-19 Add-On Study: 2,803 children (mean±standard deviation [SD], 9.0±2.7 years; range, 0-17 years) and 2,576 adults (mean±SD, 43.0±6.5 years; range, 18-85 years). We will leverage the wealth of pre-pandemic CHILD data to identify risk and resilience factors for susceptibility and severity to the direct and indirect pandemic effects. Our short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.

Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest: A Predefined Analysis of the TTM2 Randomized Clinical Trial.

Importance: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. Objectives: To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. Design, Setting, and Participants: This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. Interventions: Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). Main outcomes and measures: Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. Results: At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). Conclusions: In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common. Trial Registration: ClinicalTrials.gov Identifier: NCT02908308.

A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development.

The chemokine stromal cell-derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell alpha chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics.

The impact of COVID-19 on the eating habits of families engaged in a healthy eating pilot trial: a thematic analysis.

BACKGROUND: The eating habits of children and adults have been impacted by the COVID-19 pandemic, with evidence of increases in snacking and emotional eating, including eating to relieve boredom. We explored the experiences of families with children aged 4-8 years who had recently participated in a healthy eating pilot trial when the first national lockdown began in England. METHODS: Eleven mothers were interviewed in April and May 2020. Interview questions were developed based on the COM-B model of behaviour. Four main themes were constructed using inductive thematic analysis. RESULTS: The first theme related to an initial panic phase, in which having enough food was the primary concern. The second related to ongoing challenges during the lockdown, with sub-themes including difficulties accessing food, managing children's food requests and balancing home and work responsibilities. The perception that energy-dense foods met families' needs during this time led to increased purchasing of (and thus exposure to) energy-dense foods. In the third theme, families described a turning point, with a desire to eat a healthier diet than they had in the early stages of the lockdown. Finally, in the fourth theme, families reported a number of strategies for adapting and encouraging a balanced diet with their children. CONCLUSIONS: Our results suggest that even if parents have the capability (e.g. knowledge) and motivation to provide a healthy diet for their family, opportunity challenges (e.g. time, access to resources, environmental stressors) mean this is not always practical. Healthy eating interventions should not assume parents lack motivation and should be sensitive to the context within which parents make feeding decisions.

Adapted Behavioural Activation for Bipolar Depression: A Randomised Multiple Baseline Case Series.

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.

Do psychological interventions reduce symptoms of depression for patients with bipolar I or II disorder? A meta-analysis.

BACKGROUND: Psychological therapies may play an important role in the treatment of bipolar disorders. Several meta-analyses that examine the effectiveness of psychotherapies for patients with bipolar disorder include conclusions about the impact upon bipolar depression. However, these tend not to consider differences in depression outcome depending upon whether the therapy primarily targets acute depression, nor severity of baseline depression. This may affect the conclusions drawn about the effectiveness of these therapies for acute bipolar depression treatment. OBJECTIVES: This meta-analysis explored the effectiveness of psychological therapies in reducing bipolar depression, in particular examining whether: (1) the effect of therapy is greater when baseline depressive symptoms are more severe, and (2) the effect of therapy is greater when the primary focus of the therapy is the treatment of acute bipolar depression? DATA SOURCES: A systematic search was conducted using the following electronic databases; Cochrane Controlled Register of Trials (1996), MEDLINE (1966 onwards), EMBASE (1980 onwards), PsycINFO (1974 onwards), Scopus, Web of Science and Clinical Trials Registries (listed at:https://www.hhs.gov/ohrp/international/clinical-trial-registries/index.html). ELIGIBILITY CRITERIA: Eligible studies were randomized controlled trials evaluating a psychological intervention for adults diagnosed with Bipolar I or II disorder. The comparators were usual care, wait-list, placebo, active treatment control. Post-treatment depression status was required to be measured continuously using a validated self- or observer- report measure, or categorically by a validated diagnostic instrument or clinical diagnosis by a suitably qualified person. DATA EXTRACTION AND SYNTHESIS: Titles and abstracts were screened, followed by full texts. Two reviewers conducted each stage until agreement was reached, and both independently extracted study information. Means, standard deviations (SDs) and number of participants were retrieved from articles and used to perform a meta-analysis. The primary outcome was depressive symptom score. RESULTS: The database search identified 6388 studies. After removing the duplicates, 3298 studies remained, of which, 28 studies were included in the qualitative review and 22 in the meta-analysis. Effect sizes range from -1.99 [-2.50, -1.49] to 0.89 [-0.12, 1.90]. There was low quality evidence of a significant effect on symptoms of depression for cognitive behavioral therapy and dialectical behavior therapy. Trials of psychoeducation, mindfulness-based therapy, family therapy and interpersonal and social rhythm therapy showed no evidence of any effect on depression. We found no significant relationship between baseline depression score and depression outcome post-treatment when we controlled for therapy type and comparator. The result also showed that the effect sizes for studies targeting acute depression to be tightly clustered around a small overall effect size. CONCLUSIONS: Some psychological therapies may reduce acute bipolar depression although this conclusion should be viewed with caution given the low quality of evidence. More research using similar therapy types and comparators is needed to better understand the relationship between depression status at baseline and outcome.

How well do Cognitive Behavioural Therapy and Behavioural Activation for depression repair anhedonia? A secondary analysis of the COBRA randomized controlled trial.

A secondary analysis of the COBRA randomized controlled trial was conducted to examine how well Cognitive Behavioural Therapy (CBT) and Behavioural Activation (BA) repair anhedonia. Patients with current major depressive disorder (N = 440) were randomized to receive BA or CBT, and anhedonia and depression outcomes were measured after acute treatment (six months) and at two further follow up intervals (12 and 18 months). Anhedonia was assessed using the Snaith Hamilton Pleasure Scale (SHAPS; a measure of consummatory pleasure). Both CBT and BA led to significant improvements in anhedonia during acute treatment, with no significant difference between treatments. Participants remained above healthy population averages of anhedonia at six months, and there was no further significant improvement in anhedonia at 12-month or 18-month follow up. Greater baseline anhedonia severity predicted reduced repair of depression symptoms and fewer depression-free days across the follow-up period in both the BA and CBT arms. The extent of anhedonia repair was less marked than the extent of depression repair across both treatment arms. These findings demonstrate that CBT and BA are similarly and only partially effective in treating anhedonia. Therefore, both therapies should be further refined or novel treatments should be developed in order better to treat anhedonia.