Effectiveness of Acceptance and Commitment Therapy self-help for carers of people with multiple sclerosis: a feasibility randomised controlled trial

Objective: Acceptance and Commitment Therapy (ACT) may be a feasible, accessible and effective intervention to ‘informal’ carers of people with Multiple Sclerosis (MS) who may be experiencing strain as a result of their caring duties. The aim of this study was to assess the feasibility of randomised controlled trial (RCT) of ACT self-help, telephone-supported ACT self-help, compared to usual care (UC). Study objectives related to feasibility and acceptability of the study design and the two chosen interventions and assessing potential effectiveness at both individual and group level. Design: This study was a feasibility, mixed-methods, parallel three-armed RCT design. The three arms were: (1) ACT self-help workbook (SH), (2) ACT self-help workbook alongside weekly telephone calls (SH+), and (3) usual care. The SH group received an ACT self-help text over eight weeks, with chapters sent week-by-week via email or post. Those in the SH+ group received the intervention as those in the SH group, with the addition of weekly telephone support calls to guide them through the self-help text. Participants across all groups completed measures at baseline, at three-months and six-months post randomisation. Measures included were two measures of carer strain (Zarit Burden Interview; (ZBI) and Modified Carer Strain Index; (MCSI)), carer health-related quality of life measure (CAREQOL-MS) alongside two ACT process measures (Acceptance and Action Questionnaire; AAQ-II) and Comprehensive Assessment of Acceptance and Commitment Therapy; (CompACT). All participants randomised to the two intervention groups were invited to complete a feedback interview, which was analysed using a framework analysis to inform feasibility of the study. Results: Twenty-four self-defined primary carers of people with MS were randomised to one of the three groups previously described above. Overall, participants found the RCT design of the study to be feasible, although there were difficulties with the self-help text itself, as well as the timing of the intervention. The measures were predominantly feasible with one notable difficulty, whereby a measure of service use was omitted from the analysis and was deemed not feasible in its current form. A mixed linear model analysis showed improvement on only one outcome measure for the SH group (ZBI at 6-month follow-up), and participants reported difficulties engaging with the SH intervention in its current format. The SH+ group showed improvements on both measures of carer strain (consistent across both follow-ups) and attributed improvements both to the text as well as the telephone support. Both groups showed multiple significant improvements on process measures. Conclusions: A full trial of ACT-based, telephone-supported self-help is warranted, further to significant changes to the study design and protocol. Notably, the SH group (without telephone support) was not deemed a feasible intervention to progress to a full scale RCT, and therefore a two-armed RCT is recommended. Further work needs to be completed ahead of progressing to full trial, the major changes required would be to the intervention material and recruitment strategy. An internal pilot would, therefore, be necessary in order to assess the feasibility of the study after the suggested changes had been made. Personal reflections on the research process, chosen methodology, and intervention are offered

Descriptions of memory rehabilitation group interventions for neurological conditions: a systematic review

Objective: To establish what aspects of group-based cognitive rehabilitation for memory problems are reported, and to develop a checklist for authors, which may to improve reporting of these interventions in future studies. Data sources: A systematic search was conducted on Web of Knowledge, CINAHL, MEDLINE, AMED, EMBASE and PsycINFO electronic databases (last search: 01/05/2015). Review methods: Articles were included if the sample were adults with a neurological disorder, the intervention was group-based cognitive rehabilitation for memory problems, and if the study was a randomised controlled trial. Articles were independently screened for inclusion and data extracted by two researchers, with the third researcher arbitrating any disputes. Results: Fourteen studies were included in this review. The reporting of certain aspects of an intervention was found to be poor, particularly in relation to: duration of the programme (6 of 14 studies did not report), the development of the intervention (7 of 14 studies did not discuss), and the content and structure of intervention (7 of the 14 studies did not provide details). Conclusion: This review found that the overall reporting of memory rehabilitation content and format is poor. Refinement and adaption of pre-existing checklists to capture aspects of cognitive rehabilitation programmes may help authors when reporting complex interventions. A draft checklist is provided that could be refined and validated in further research

Mindfulness self-help interventions for symptoms of depression, anxiety and stress: review and meta-analysis

Background: Mindfulness-based therapy has been found to be an efficacious treatment for a range of mental and physical health conditions. There are increasing efforts to deliver benefits of mindfulness through less intensive/more accessible modalities but whether this efficacy holds in lower-intensity forms is unknown. This paper reviews the effectiveness of mindfulness delivered in a self-help manner for reducing symptoms of anxiety, depression and stress. Methods: We conducted a systematic search on a number of databases. Data were analysed with primary outcome measures of depression, anxiety and stress, and a secondary outcome of mindfulness. Sub-group analyses were completed for active control versus passive control. Findings: Analyses revealed statistically significant differences for primary and secondary outcomes, favouring the intervention group. Sub-group analyses were conducted for depression and anxiety (passive control) and depression (active control) and showed no significant differences. Discussion: There is support for the use of mindfulness in a self-help format, although there are relatively few studies and sample sizes are generally small. The high heterogeneity reduces the potential impact of these findings as well as mixed ratings for risk of bias within studies. Limitations of this review and implications for future research are discussed

A meta-synthesis of qualitative research on perceptions of people with long-term neurological conditions about group-based memory rehabilitation

The effectiveness of memory rehabilitation based on randomised controlled trials and meta-analyses has been inconclusive, but patient reports based on qualitative studies have been largely positive. We conducted a meta-synthesis of qualitative studies of group-based memory rehabilitation programmes for people with neurological conditions. Based on systematic searches of electronic databases and reference lists, five papers (87 participants) were selected. Quality appraisal of papers was conducted by two independent reviewers using the Critical Appraisal Skills Programme tool. Data synthesis was guided by the meta-ethnography approach. Fiver higher order themes were elicited. These suggested that memory rehabilitation was associated with insight and acceptance of participants’ neurological condition and resultant cognitive deficits. The therapeutic effects of the groups, with social support and leisure activities, helped with participants’ confidence. There were improvements in memory related to better self-awareness and learning to use new skills and strategies to compensate for memory deficits. These improvements also related to other psychological effects, in terms of positively affected mood, confidence and fatigue. Ultimately, these changes had a positive impact on daily life, with changes seen in the personal, inter-personal and professional spheres. Therefore, this synthesis of qualitative studies suggests that memory rehabilitation offers positive outcomes for people with long-term neurological conditions

Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II:Multi-Institutional Propensity Score Matched Analysis

BACKGROUND: In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown. STUDY DESIGN: SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma-specific mortality were compared. RESULTS: Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p 3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/ or >3 positive SLN

Active surveillance of patients who have sentinel node positive melanoma:An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy trial II (MSLT-2)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168248/1/cncr33483.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168248/2/cncr33483_am.pd

Loss of Cardioprotective Effects at the ADAMTS7 Locus as a Result of Gene-Smoking Interactions

BACKGROUND: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk. METHODS: We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a P value of <1.0x10(-3) (Bonferroni correction for 50 tests). RESULTS: We identified novel gene-smoking interaction for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (P= 1.3x10(-16)) in comparison with 5% in ever-smokers (P= 2.5x10(-4)), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction P value= 8.7x10(-5)). The protective T allele at rs7178051 was also associated with reduced ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of ADAMTS7. CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced ADAMTS7 expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular ADAMTS7 expression may contribute to the loss of CHD protection in smokers.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat