Mindfulness-Based Online Intervention to Improve Quality of Life in Late-Stage Bipolar Disorder:A Randomized Clinical Trial

Objective: Adjunctive psychological interventions improve outcomes in bipolar disorder (BD), but people in latter stages likely have different clinical needs. The objective here was to test the hypothesis that for people with ≥⃒ 10 episodes of BD, a brief online mindfulness-based intervention (ORBIT 2.0) improves quality of life (QoL) relative to a Psychoeducation control. Method: A rater-masked, pragmatic superiority randomized clinical trial compared ORBIT 2.0 with active control. Both interventions were 5-week coach-supported programs with treatment as usual continued. Inclusion criteria included age 18–65 years, confirmed diagnosis of BD, and history of ≱ 10 episodes. Measures were collected at baseline, postintervention, and 3 and 6-month follow-ups. The main outcome was QoL, measured on the Brief Quality of Life in Bipolar Disorder (Brief QoL.BD) at 5 weeks, using intentiont treat analyses. Results: Among N = 302 randomized participants, the primary hypothesis was not supported (Treatment × Time β = −0.69, 95% CI [−2.69, 1.31], p =.50). The main effect of Time was not significant in either condition, indicating no improvement in either group. Recruitment was feasible, the platform was safe, both interventions were highly acceptable, but usage was suboptimal. Post hoc analyses found both interventions effective for participants not in remission from depression at baseline.Conclusions: In people with late-stage BD, an online mindfulness-based intervention was not superior to psychoeducational control in improving QoL. Online delivery was found to be safe and acceptable.Future interventions may need to be higher intensity, address engagement challenges, and target more symptomatic individual

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Online mindfulness-based interventions for late-stage bipolar disorder

Objectives People in the late stage of bipolar disorder (BD) experience elevated relapse rates and poorer quality of life (QoL) compared with those in the early stages. Existing psychological interventions also appear less effective in this group. To address this need, we developed a new online mindfulness-based intervention targeting quality of life (QoL) in late stage BD. Here, we report on an open pilot trial of ORBIT (online, recovery-focused, bipolar individual therapy). Methods Inclusion criteria were: self-reported primary diagnosis of BD, six or more episodes of BD, under the care of a medical practitioner, access to the internet, proficient in English, 18–65 years of age. Primary outcome was change (baseline – post-treatment) on the Brief QoL.BD (Michalak and Murray, 2010). Secondary outcomes were depression, anxiety, and stress measured on the DASS scales (Lovibond and Lovibond, 1993). Results Twenty-six people consented to participate (Age M=46.6 years, SD=12.9, and 75% female). Ten participants were lost to follow-up (38.5% attrition). Statistically significant improvement in QoL was found for the completers, t(15)=2.88, 95% CI:.89–5.98, p=.011, (Cohen׳s dz=.72, partial η2=.36), and the intent-to-treat sample t(25)=2.65, 95% CI:.47–3.76, (Cohen׳s dz=.52; partial η2=.22). A non-significant trend towards improvement was found on the DASS anxiety scale (p=.06) in both completer and intent-to-treat samples, but change on depression and stress did not approach significance. Limitations This was an open trial with no comparison group, so measured improvements may not be due to specific elements of the intervention. Structured diagnostic assessments were not conducted, and interpretation of effectiveness was limited by substantial attrition. Conclusion Online delivery of mindfulness-based psychological therapy for late stage BD appears feasible and effective, and ORBIT warrants full development. Modifications suggested by the pilot study include increasing the 3 weeks duration of the intervention, adding cautions about the impact of extended meditations, and addition of coaching support/monitoring to optimise engagement