Abstract Purpose The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers. Methods Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient). Metabolite fingerprinting was carried out by flow infusion electrospray ionisation high-resolution mass spectrometry and metabolomic data were analysed using the R-based platform MetaboAnalyst. The metabolites were identified using DIMEdb (dimedb.ibers.aber.ac.uk) from their mass/charge ratios. These metabolomic data were also re-analysed using individual and cluster-level analysis. The individual-level models were adjusted for confounders, such as age, sex, noradrenaline dosage and patient (random effect). Results Analysis was undertaken at cluster- and individual-level. There were no significant differences in cytokine concentration level between trial arms nor survivors and non-survivors over the duration of the observations from day 1 to day 4. Metabolomic analysis showed some separation in the levels of ceramides and cardiolipins between those who survived and those who died. Following adjusted analysis for confounders, plasma metabolite concentrations remained statistically different between landiolol and standard care arms for succinic acid, l -tryptophan, l -alanine, 2,2,2-trichloroethanol, lactic acid and d -glucose. Conclusions In a study of ICU patients with established septic shock and a tachycardia, landiolol treatment used to reduce the heart rate from above 95 to a range between 80 and 94 beats per minute did not induce significant cytokine changes. d -Glucose, lactic acid, succinic acid, l -alanine, l -tryptophan and trichloroethanol were pathways that may merit further investigation. Trial Registration : EU Clinical Trials Register Eudra CT: 2017-001785-14 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001785-14/GB ); ISRCTN registry Identifier: ISRCTN12600919 ( https://www.isrctn.com/ISRCTN12600919 ).
Abstract Background Although multiple qualitative studies have explored participants' experiences of behavioural activation (BA) for unipolar depression, none have investigated the experiences of BA in people with bipolar depression. This is of particular interest because qualitative studies concerning the experience of receiving therapy can help inform the theory of change underpinning the intervention. Aim The purpose of this study was to explore the experiences and perspectives of individuals with bipolar disorder who received a course of one‐to‐one BA for bipolar depression. We sought to explore participants' experience of the effects of BA therapy, both proximally and distally. Method Semi‐structured interviews were conducted with nine individuals meeting research diagnostic criteria for bipolar I or II disorder who had received up to 20 sessions of BA adapted for bipolar depression. Thematic analysis using a framework approach was used to explore and describe the experiences of participants. Results Participants' perspectives on the impact of therapy were categorized under four subthemes: client behaviour inside and outside sessions, changes in clients' perspectives, the impact on symptoms and impact on life and functioning. Conclusions Participants' accounts of the impact of therapy were broadly consistent with the theory underpinning a behavioural approach. Participants described a central role for perspective change, and particularly increased acceptance of the self and mood states, as facilitating behavioural changes and more distal benefits. Process evaluations embedded in future trials may include quantitative measures of key processes described by our participants, as well as those clearly implied by the behavioural theory of depression.
Abstract The majority of research into the mental health benefits of blue space (outdoor places where water is a central feature) has focussed on the associations between neighbourhood exposure to these spaces and population‐level incidence of unipolar depression or anxiety disorder. There has been little exploration of the therapeutic use of blue space by those navigating bipolar, schizophrenia or other psychotic conditions. Knowledge arising from such an exploration could assist in the design and optimisation of nature‐based care for people with these conditions, as well as with self‐management. We conducted semi‐structured online and telephone interviews with 19 adults who self‐reported experience of these conditions. Interviews were conducted in the United Kingdom from August to December 2021. We describe four of the key interpretive themes identified via an in‐depth inductive thematic analysis of the interview transcripts to highlight how participants sought out moments of affective sanctuary through their blue encounters. Blue spaces were described as having the potential to reset the mind, emotions and body. This was in part due to their socially undemanding nature, and ability to provide respite from a socially stressful world. Participants described developing a blue identity, whereby a sense of attachment to and shared history with these places was articulated as well as incorporating blue spaces into self‐ and emotion‐regulation practices. Finally, participants described experiences of and recommendations for a therapeutic blue intervention. The role of biodiversity in contributing to the benefits of blue spaces was implied primarily in terms of perceived soundscapes, but also through visual observations. Synthesis and applications . Blue care for people with bipolar, schizophrenia or other psychotic conditions should consider the need that some individuals have for solitude and proximity to their home when they visit blue spaces, as well as individual differences in the features of blue space interactions that provide the greatest benefit. Read the free Plain Language Summary for this article on the Journal blog.
In bipolar spectrum disorder, some individuals experience ongoing, frequent fluctuations in mood outside of affective episodes. There are currently no evidence-based psychological interventions designed to address this. This feasibility study is a phase II evaluation of a dialectical behavioural therapy-informed approach (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). It seeks to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. Patients will be randomised 1:1 to either treatment as usual only (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points will be at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point for the candidate primary outcome measures. We aim to recruit 48 individuals meeting diagnostic criteria for a bipolar spectrum disorder and reporting frequent mood swings outside of acute episodes, through primary and secondary care services and self-referral. To evaluate feasibility and acceptability, we will examine recruitment and retention rates, completion rates for study measures and feedback from participants on their experience of study participation and therapy. Proceeding to a definitive trial will be indicated if the following criteria are met: (1) trial participation does not lead to serious negative consequences for our participants; (2) any serious concerns about the acceptability and feasibility of the trial procedures can be rectified prior to a definitive trial; (3) follow-up data at 9 months are available for at least 60% of participants; (4) at least 60% of patients in the ThrIVe-B arm complete treatment. ISRCTN, ISRCTN54234300 . Registered on 20 July 2017.
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.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.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.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).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.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%).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.ClinicalTrials.gov Identifier: NCT02908308.
We have reported the advantageous clinical outcome of adding cognitive therapy to medication in the prevention of relapse of bipolar disorder.This 30-month study compares the cost-effectiveness of cognitive therapy with standard care.We randomly allocated 103 individuals with bipolar 1 disorder to standard treatment and cognitive therapy plus standard treatment. Service use and costs were measured at 3-month intervals and cost-effectiveness was assessed using the net-benefit approach.The group receiving cognitive therapy had significantly better clinical outcomes. The extra costs were offset by reduced service use elsewhere. The probability of cognitive therapy being cost-effective was high and robust to different therapy prices.Combination of cognitive therapy and mood stabilizers was superior to mood stabilizers alone in terms of clinical outcome and cost-effectiveness for those with frequent relapses of bipolar disorder.
Background Depression is a common, debilitating and costly disorder. The best-evidenced psychological therapy – cognitive–behavioural therapy (CBT) – is complex and costly. A simpler therapy, behavioural activation (BA), may be an effective alternative. Objectives To determine the clinical effectiveness and cost-effectiveness of BA compared with CBT for depressed adults at 12 and 18 months’ follow-up, and to investigate the processes of treatments. Design Randomised controlled, non-inferiority trial stratified by depression severity, antidepressant use and recruitment site, with embedded process evaluation; and randomisation by remote computer-generated allocation. Setting Three community mental health services in England. Participants Adults aged ≥ 18 years with major depressive disorder (MDD) recruited from primary care and psychological therapy services. Interventions BA delivered by NHS junior mental health workers (MHWs); CBT by NHS psychological therapists. Outcomes Primary: depression severity (as measured via the Patient Health Questionnaire-9; PHQ-9) at 12 months. Secondary: MDD status; number of depression-free days; anxiety (as measured via the Generalised Anxiety Disorder-7); health-related quality of life (as measured via the Short Form questionnaire-36 items) at 6, 12 and 18 months; and PHQ-9 at 6 and 18 months, all collected by assessors blinded to treatment allocation. Non-inferiority margin was 1.9 PHQ-9 points. We undertook intention-to-treat (ITT) and per protocol (PP) analyses. We explored cost-effectiveness by collecting direct treatment and other health- and social-care costs and calculating quality-adjusted life-years (QALYs) using the EuroQol-5 Dimensions, three-level version, at 18 months. Results We recruited 440 participants (BA, n = 221; CBT, n = 219); 175 (79%) BA and 189 (86%) CBT participants provided ITT data and 135 (61%) BA and 151 (69%) CBT participants provided PP data. At 12 months we found that BA was non-inferior to CBT {ITT: CBT 8.4 PHQ-9 points [standard deviation (SD) 7.5 PHQ-9 points], BA 8.4 PHQ-9 points (SD 7.0 PHQ-9 points), mean difference 0.1 PHQ-9 points, 95% confidence interval (CI) –1.3 to 1.5 PHQ-9 points, p = 0.89; PP: CBT 7.9 PHQ-9 points (SD 7.3 PHQ-9 points), BA 7.8 PHQ-9 points (SD 6.5 PHQ-9 points), mean difference 0.0 PHQ-9 points, 95% CI –1.5 to 1.6 PHQ-9 points, p = 0.99}. We found no differences in secondary outcomes. We found a significant difference in mean intervention costs (BA, £975; CBT, £1235; p < 0.001), but no differences in non-intervention (hospital, community health, social care and medication costs) or total (non-intervention plus intervention) costs. Costs were lower and QALY outcomes better in the BA group, generating an incremental cost-effectiveness ratio of –£6865. The probability of BA being cost-effective compared with CBT was almost 80% at the National Institute for Health and Care Excellence’s preferred willingness-to-pay threshold of £20,000–30,000 per QALY. There were no trial-related adverse events. Limitations In this pragmatic trial many depressed participants in both groups were also taking antidepressant medication, although most had been doing so for a considerable time before entering the trial. Around one-third of participants chose not to complete a PP dose of treatment, a finding common in both psychotherapy trials and routine practice. Conclusions We found that BA is as effective as CBT, more cost-effective and can be delivered by MHWs with no professional training in psychological therapies. Future work Settings and countries with a paucity of professionally qualified psychological therapists, might choose to investigate the delivery of effective psychological therapy for depression without the need to develop an extensive and costly professional infrastructure. Trial registration Current Controlled Trials ISRCTN27473954. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 46. See the NIHR Journals Library website for further project information.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
