Displacement Encoding With Stimulated Echoes Enables the Identification of Infarct Transmurality Early Postmyocardial Infarction.

BACKGROUND: Segmental extent of infarction assessed by late gadolinium enhancement (LGE) imaging early post-ST-segment elevation myocardial infarction (STEMI) has utility in predicting left ventricular functional recovery. HYPOTHESIS: We hypothesized that segmental circumferential strain with displacement encoding with stimulated echoes (DENSE) would be a stronger predictor of infarct transmurality than feature-tracking strain, and noninferior to extracellular volume fraction (ECV). STUDY TYPE: Prospective. POPULATION: Fifty participants (mean ± SD, 59 ± 9 years, 40 [80%] male) underwent cardiac MRI on day 1 post-STEMI. FIELD-STRENGTH/SEQUENCES: 1.5T/cine, DENSE, T1 mapping, ECV, LGE. ASSESSMENT: Two observers assessed segmental percentage LGE extent, presence of microvascular obstruction (MVO), circumferential and radial strain with DENSE and feature-tracking, T1 relaxation times, and ECV. STATISTICAL TESTS: Normality was tested using the Shapiro-Wilk test. Skewed distributions were analyzed utilizing Mann-Whitney or Kruskal-Wallis tests and normal distributed data using independent t-tests. Diagnostic cutoff values were identified using the Youden index. The difference in area under the curve was compared using the z-statistic. RESULTS: Segmental circumferential strain with DENSE was associated with the extent of infarction ≥50% (AUC [95% CI], cutoff value = 0.9 [0.8, 0.9], -10%) similar to ECV (AUC = 0.8 [0.8, 0.9], 37%) (P = 0.117) and superior to feature-tracking circumferential strain (AUC = 0.7[0.7, 0.8], -19%) (P < 0.05). For the detection of segmental infarction ≥75%, circumferential strain with DENSE (AUC = 0.9 [0.8, 0.9], -10%) was noninferior to ECV (AUC = 0.8 [0.7, 0.9], 42%) (P = 0.132) and superior to feature-tracking (AUC = 0.7 [0.7, 0.8], -13%) (P < 0.05). For MVO detection, circumferential strain with DENSE (AUC = 0.8 [0.8, 0.9], -12%) was superior to ECV (AUC = 0.8 [0.7, 0.8] 34%) (P < 0.05) and feature-tracking (AUC = 0.7 [0.6, 0.7] -21%) (P < 0.05). DATA CONCLUSION: Circumferential strain with DENSE is a functional measure of infarct severity and may remove the need for gadolinium contrast agents in some circumstances. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 5 J. MAGN. RESON. IMAGING 2020;52:1722-1731.

Circumferential Strain Predicts Major Adverse Cardiovascular Events Following an Acute ST-Segment-Elevation Myocardial Infarction.

Purpose To investigate the prognostic value of circumferential left ventricular (LV) strain measured by using cardiac MRI for prediction of major adverse cardiac events (MACE) following an acute ST-segment-elevation myocardial infarction (STEMI). Materials and Methods Participants with acute STEMI were prospectively enrolled from May 11, 2011, to November 22, 2012. Cardiac MRI was performed at 1.5 T during the index hospitalization. Displacement encoding with stimulated echoes (DENSE) and feature tracking of cine cardiac MRI was used to assess circumferential LV strain. MACE that occurred after discharge were independently assessed by cardiologists blinded to the baseline observations. Results A total of 259 participants (mean age, 58 years ± 11 [standard deviation]; 198 men [mean age, 58 years ± 11] and 61 women [mean age, 58 years ± 12]) underwent cardiac MRI 2.2 days ± 1.9 after STEMI. Average infarct size was 18% ± 13 of LV mass and circumferential strain was -13% ± 3 (DENSE method) and -24% ± 7 (feature- tracking method). Fifty-one percent (131 of 259 participants) had presence of microvascular obstruction. During a median follow-up period of 4 years, 8% (21 of 259) experienced MACE. Area under the curve (AUC) for DENSE was different from that of feature tracking (AUC, 0.76 vs 0.62; P = .03). AUC for DENSE was similar to that of initial infarct size (P = .06) and extent of microvascular obstruction (P = .08). DENSE-derived strain provided incremental prognostic benefit over infarct size for prediction of MACE (hazard ratio, 1.3; P < .01). Conclusion Circumferential strain has independent prognostic importance in study participants with acute ST-segment-elevation myocardial infarction. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Kramer in this issue.

Reactive Attachment Disorder in maltreated young children in foster care.

Reactive attachment disorder (RAD) is one of the least researched and most poorly understood psychiatric disorders. Very little is known about the prevalence and stability of RAD symptoms over time. Until recently it has been difficult to investigate RAD due to limited tools for informing a diagnosis. Utilising a newly developed observational tool along with the Disturbances of Attachment Interview. this short-term prospective longitudinal study explored RAD symptoms in maltreated young children in Scotland (n=100, age range =12-62 months) over 12 months. Children were recruited as part of The Best Services Trial (BeST?), in which all infants who came in to the care of the local authority in Glasgow due to child protection concerns were invited to participate. Prevalence of RAD was found to be 5.0% (n=5, 95% CI [0.7-9.3]) when children were first placed in to foster care. Following at least 1 year of improved care conditions, prevalence in the 76 children remaining in the study was 2.1% (n=2, 95% CI [below 0-4.7]). RAD was associated with some mental health and cognitive difficulties. While levels of carer-reported RAD symptoms decreased significantly over time, observed symptoms did not. Findings suggest that RAD resolved in a small majority of cases but further exploration in larger samples would be invaluable.

Community-based group guided self-help intervention for low mood and stress: randomised controlled trial.

BACKGROUND: To date no studies have explored the effectiveness of written cognitive-behavioural therapy (CBT) resources for low mood and stress delivered via a course of self-help classes in a community setting. Aims To assess the effectiveness of an 8-week community-based CBT self-help group classes on symptoms of depression, anxiety and social function at 6 months (trial registration: ISRCTN86292664). METHOD: In total, 142 participants were randomly allocated to immediate (n = 71) or delayed access to a low-intensity CBT intervention (n = 71). Measures of depression, anxiety and social function were collected at baseline and 6 months. RESULTS: There was a significant improvement for the primary outcome of Patient Health Questionnaire-9 (PHQ-9) score (mean between-group difference: -3.64, 95% CI -6.06 to -1.23; P = 0.004). The percentage of participants reducing their PHQ-9 score between baseline and 6 months by 50% or more was 17.9% for the delayed access group and 43.8% for the immediate access group. Secondary outcomes also improved including anxiety and social function. The intervention was cost neutral. The probabilities of a net benefit at willingness to pay thresholds of £20 000, £25 000 or £30 000 were 0.928, 0.944 and 0.955, respectively. CONCLUSIONS: Low-intensity class-based CBT delivered within a community setting is effective for reducing depression, anxiety and impaired social function at little additional cost. Declaration of interest C.W. is president of British Association for Behavioural & Cognitive Psychotherapies (BABCP) - the lead body for CBT in the UK. He is also author of a range of CBT-based resources available commercially. He is developer of the LLTTF classes evaluated in this study. He receives royalty, and is shareholder and director of a company that commercialises these resources.

Positive PsychoTherapy in ABI Rehab (PoPsTAR): A pilot randomised controlled trial.

Psychological distress is common following acquired brain injury (ABI), but the evidence base for psychotherapeutic interventions is small and equivocal. Positive psychotherapy aims to foster well-being by increasing experiences of pleasure, engagement and meaning. In this pilot trial, we investigated the feasibility and acceptability of brief positive psychotherapy in adults with ABI and emotional distress. Participants were randomised to brief positive psychotherapy plus usual treatment, or usual treatment only. Brief positive psychotherapy was delivered over eight individual out-patient sessions, by one research psychologist. A blinded assessor administered the Depression Anxiety Stress Scales (DASS-21) and the Authentic Happiness Inventory (AHI) at 5, 9 and 20 weeks post-baseline. Of 27 participants randomised (median age 57; 63% male; 82% ischaemic stroke survivors; median 5.7 months post-injury), 14 were assigned to positive psychotherapy, of whom 8 completed treatment. The intervention was feasible to deliver with excellent fidelity, and was acceptable to participants. Retention at 20 weeks was 63% overall. A full-scale trial would need to retain n = 39 per group to end-point, to detect a significant difference in change scores on the DASS-21 Depression scale of 7 points (two-tailed alpha = .05, power = .80). Trials including an active control arm would require larger sample sizes. We conclude that a full-scale trial to investigate efficacy is warranted.

Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients With an Acute ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Primary percutaneous coronary intervention is frequently successful at restoring coronary artery blood flow in patients with acute ST-segment-elevation myocardial infarction; however, failed myocardial reperfusion commonly passes undetected in up to half of these patients. The index of microvascular resistance (IMR) is a novel invasive measure of coronary microvascular function. We aimed to investigate the pathological and prognostic significance of an IMR>40, alone or in combination with a coronary flow reserve (CFR≤2.0), in the culprit artery after emergency percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction. METHODS: Patients with acute ST-segment-elevation myocardial infarction were prospectively enrolled during emergency percutaneous coronary intervention and categorized according to IMR (≤40 or >40) and CFR (≤2.0 or >2.0). Cardiac magnetic resonance imaging was acquired 2 days and 6 months after myocardial infarction. All-cause death or first heart failure hospitalization was a prespecified outcome (median follow-up, 845 days). RESULTS: IMR and CFR were measured in the culprit artery at the end of percutaneous coronary intervention in 283 patients with ST-segment-elevation myocardial infarction (mean±SD age, 60±12 years; 73% male). The median IMR and CFR were 25 (interquartile range, 15-48) and 1.6 (interquartile range, 1.1-2.1), respectively. An IMR>40 was a multivariable associate of myocardial hemorrhage (odds ratio, 2.10; 95% confidence interval, 1.03-4.27; P=0.042). An IMR>40 was closely associated with microvascular obstruction. Symptom-to-reperfusion time, TIMI (Thrombolysis in Myocardial Infarction) blush grade, and no (≤30%) ST-segment resolution were not associated with these pathologies. An IMR>40 was a multivariable associate of the changes in left ventricular ejection fraction (coefficient, -2.12; 95% confidence interval, -4.02 to -0.23; P=0.028) and left ventricular end-diastolic volume (coefficient, 7.85; 95% confidence interval, 0.41-15.29; P=0.039) at 6 months independently of infarct size. An IMR>40 (odds ratio, 4.36; 95% confidence interval, 2.10-9.06; P<0.001) was a multivariable associate of all-cause death or heart failure. Compared with an IMR>40, the combination of IMR>40 and CFR≤2.0 did not have incremental prognostic value. CONCLUSIONS: An IMR>40 is a multivariable associate of left ventricular and clinical outcomes after ST-segment-elevation myocardial infarction independently of the infarction size. Compared with standard clinical measures of the efficacy of myocardial reperfusion, including the ischemic time, ST-segment elevation, angiographic blush grade, and CFR, IMR has superior clinical value for risk stratification and may be considered a reference test for failed myocardial reperfusion. CLINICAL TRIAL REGISTRATION: URL: https//www.clinicaltrials.gov. Unique identifier: NCT02072850.

Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study.

BACKGROUND: CTX0E03 is an immortalised human neural stem-cell line from which a drug product (CTX-DP) was developed for allogeneic therapy. Dose-dependent improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients. METHODS: We did an open-label, single-site, dose-escalation study. Men aged 60 years or older with stable disability (National Institutes of Health Stroke Scale [NIHSS] score ≥6 and modified Rankin Scale score 2-4) 6-60 months after ischaemic stroke were implanted with single doses of 2 million, 5 million, 10 million, or 20 million cells by stereotactic ipsilateral putamen injection. Clinical and brain imaging data were collected over 2 years. The primary endpoint was safety (adverse events and neurological change). This trial is registered with ClinicalTrials.gov, number NCT01151124. FINDINGS: 13 men were recruited between September, 2010, and January, 2013, of whom 11 (mean age 69 years, range 60-82) received CTX-DP. Median NIHSS score before implantation was 7 (IQR 6-8) and the mean time from stroke was 29 (SD 14) months. Three men had subcortical infarcts only and seven had right-hemisphere infarcts. No immunological or cell-related adverse events were seen. Other adverse events were related to the procedure or comorbidities. Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients. At 2 years, improvement in NIHSS score ranged from 0 to 5 (median 2) points. INTERPRETATION: Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function. Our observations support further investigation of CTX-DP in stroke patients. FUNDING: ReNeuron Limited.

Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors.

AIMS: To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. CONCLUSION: Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted. CLINICALTRIALS. GOV IDENTIFIER: NCT02072850.

A community-based pilot randomised controlled study of life skills classes for individuals with low mood and depression.

BACKGROUND: Cognitive behavioural therapy (CBT) is recommended for the treatment of depression and anxiety. However, access is limited. Low-intensity approaches such as guided CBT self-help (bibliotherapy) can increase access to treatment and is recommended by UK guidelines. No previous research has explored the provision of group-based guidance/support for a bibliotherapy approach for depression and anxiety in community settings. The objective was to carry out a pilot study of a group guided self-help intervention, using community based recruitment methods. METHOD: A randomised controlled trial comparing an 8 week CBT group guided self-help intervention to usual care. Recruitment and the delivery of the intervention were carried out in Glasgow and Derry/Londonderry in partnership with national depression charities. Fifty-three people were randomised, however we refer only to the forty-six participants who provided baseline data: 16 males and 30 females, aged 16 or over, with a PHQ-9 score of ≥ 5, were recruited from the community. The mean age of the sample was 43.7 (sd = 13) and 93.5% of participants had suffered from low mood for a year or more. RESULTS: There was effective recruitment, randomisation, uptake and adherence with 21 Immediate Access (IA) and 25 Delayed Access Control (DAC) participants. The intervention was highly acceptable to participants attending on average 4.46 of the 8 sessions (sd 3.06), 65.2% attended more than half of all sessions. The mean satisfaction on the Client Satisfaction Questionnaire was 28 out of 32 (sd 4.8). The provisional results in the pilot suggest the intervention may improve both anxiety and depression. At three months, data collection was achieved from 74% of participants. The trial successfully provided estimates of the sample size needed for the future planned trial. CONCLUSIONS: Low-intensity group-based classes may offer an alternative method of managing depression and anxiety and warrant further research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84893887 . Registered 3 November 2011.

Towards system redesign: An exploratory analysis of neurodivergent traits in a childhood population referred for autism assessment.

BACKGROUND: Children's health services in many countries are moving from single condition diagnostic silo assessments to considering neurodevelopment in a more holistic sense. There has been increasing recognition of the importance of clinical overlap and co-occurrence of different neurotypes when assessing neurodivergent children. Using a cross-sectional service evaluation design, we investigated the overlap of neurodivergences in a cohort of children referred for autism assessment, focusing on motor, learning, and attention/activity level domains. We aimed to determine what proportion of children in a cohort referred for an autism assessment showed traits of additional neurodivergences, and what proportion were further investigated. METHODS: We evaluated anonymised medical records of children aged between two and 17 years referred for autism assessment. We used validated questionnaires to assess for neurodivergent traits. A weighted scoring system was developed to determine traits in each neurodevelopmental domain and a score above the median was considered to indicate a neurodivergent trait. Evidence of further investigations were recorded. We then examined the relationships between autism traits and traits of additional neurodivergence. RESULTS: 114 participants were included for evaluation. 62.3% (n = 71) had completed questionnaires for analysis. Of these, 71.8% (n = 51) scored greater than the median for at least one additional neurotype, indicating the presence of other neurodivergent traits, and 88.7% (n = 64) attracted a diagnosis of autism. Only 26.3% of children with evidence of additional neurotypes were further investigated beyond their autism assessment. CONCLUSIONS: Our results demonstrate the extensive overlap between additional neurodivergent traits in a population of children referred with suspected autism and show that only a small proportion were further investigated. The use of standardised questionnaires to uncover additional neurodivergences may have utility in improving the holistic nature of neurodevelopmental assessments.

Baseline Characteristics in the Remote Diet Intervention to REduce long-COVID Symptoms Trial (ReDIRECT).

Background: The persistence of symptoms for ≥12 weeks after a COVID-19 infection is known as Long COVID (LC), a condition with unclear pathophysiology and no proven treatments to date. Living with obesity is a risk factor for LC and has symptoms which may overlap with and aggravate LC. Methods: ReDIRECT is a remotely delivered trial assessing whether weight management can reduce LC symptoms. We recruited people with LC and BMI >27kg/m 2. The intervention was delivered remotely by dietitians, with online data collection (medical and dietary history, COVID-19 infection and vaccination, body composition, LC history/symptoms, blood pressure, quality of life, sociodemographic data). Participants self-selected the dominant LC symptoms they most wanted to improve from the intervention. Results: Participants (n=234) in England (64%) and Scotland (30%) were mainly women (85%) of white ethnicity (90%), with 13% living in the 20% most deprived areas, a mean age of 46 (SD10) years, and median BMI of 35kg/m 2 (IQR 32-40). Before starting the study, 30% reported more than one COVID-19 infection (82% confirmed with one or more positive tests). LC Diagnosis was mainly by GPs (71%), other healthcare professionals (9%), or self-diagnosed (21%). The median total number of symptoms was 6 (IQR 4-8). Self-selected dominant LC symptoms included fatigue (54%), breathlessness (16%), pain (12%), anxiety/depression (1%) and "other" (17%). At baseline, 82% were taking medication, 57% reported 1+ other medical conditions. Quality of life was poor; 20% were on long-term sick leave or reduced working hours. Most (92%) reported having gained weight since contracting COVID-19 (median weight change +11.5 kg, range -11.5 to +45.3 kg). Conclusions: Symptoms linked to LC and overweight are diverse and complex. Remote trial delivery enabled rapid recruitment across the UK yet certain groups (e.g. men and those from ethnic minority groups) were under-represented. Trial registration: ISRCTN registry ( ISRCTN12595520, 25/11/2021).

Long COVID (LC, symptoms lasting 12 weeks or more after a COVID-19 infection) is a poorly understood condition, with no proven treatments. Living with obesity increases the risk of developing LC; symptoms of obesity overlap and aggravate those of LC. The ReDIRECT study tests, in people living with both LC and overweight, whether weight management can reduce LC symptoms. The study involves total diet replacement (with porridge, soups and shakes) for 12 weeks and is delivered remotely, with dietitian support via internet and/or phone. Researchers collected all data via online forms (medical and diet history, COVID-19 infection and vaccination, weight, height, LC history and symptoms, blood pressure, quality of life, and other demographic data). Each participant selected the LC symptom they most wanted to see improve. Participants (n=234) lived across the UK, were mainly women (85%) of white ethnicity (90%), with 13% living in the 20% most deprived areas. Their average age was 46 years old with an average body mass index (BMI) of 35kg/m ². Diagnosis of LC was mainly by GPs (71%), other healthcare professionals (9%), or self-diagnosed (21%). Participants reported on average 6 symptoms each, identifying fatigue (54%), breathlessness (16%), pain (12%), anxiety/depression (1%) and "other" (17%) as the symptom they would most like to see improve. At the start of the study, most (82%) were taking medication, half (57%) reported 1+ other medical conditions. Quality of life was poor, and 20% were on long-term sick leave or reduced working hours. Most (92%) reported gaining weight since contracting COVID-19, on average +11.5 kg. The baseline characteristics of ReDIRECT study participants show that symptoms linked to LC and overweight are diverse and complex. The study being "remote" means that recruitment was rapid and across the UK, yet certain groups (e.g. men and those from ethnic minority groups) were under-represented.

Assessing the optimal time interval between growth measurements using a combined data set of weights and heights from 5948 infants.

BACKGROUND: Current guidance on the optimum interval between measurements in infancy is not evidence based. We used routine data to explore how measurement error and short-term variation ('noise') might affect interpretation of infant weight and length gain ('signal') over different time intervals. METHOD: Using a database of weights and lengths from 5948 infants aged 0-12 months, all pairs of measurements per child 2, 4 and 8 weeks apart were extracted. Separately, 20 babies aged 2-10 months were weighed on six occasions over 3 days to estimate the SD of the weight difference between adjacent measurements (=116 g). Values of 116 g and 0.5 cm for 'noise' were then used to model its impact on (a) the estimated velocity centile and (b) the chance of seeing no growth during the interval, in individuals. RESULTS: The average gain in weight and length was much larger than the corresponding SD over 8-week and 4-week time intervals, but not over 2 weeks. Noise tended to make apparent velocity less extreme; after age 6 months, a 2-week velocity that appeared to be on to the ninth centile, would truly be on the second-third centile if measured with no noise. For 2-week intervals, there was a 16% risk of no apparent growth by age 10 months. CONCLUSIONS: Growth in infancy is so rapid that the change in measurements 4-8 weeks apart is unlikely ever to be obscured by noise, but after age 6 months, measurements 2 weeks or less apart should be treated with caution when assessing growth faltering.

Online Cognitive Behavioral Therapy (CBT) Life Skills Program for Depression: Pilot Randomized Controlled Trial.

BACKGROUND: Depression is a common mental health problem with significant personal and social consequences. Studies have suggested that cognitive behavioral therapy (CBT) is an effective treatment for depression and anxiety when delivered one-to-one by an expert practitioner, but access to this talking therapy is often limited, and waiting lists can be long. However, a range of low-intensity interventions that can increase access to services are available including guided CBT self-help materials delivered via books, classes, and online packages. OBJECTIVE: This project aimed to pilot a randomized controlled trial (RCT) of an online CBT-based life skills course with community-based individuals experiencing depression. METHODS: Individuals with symptoms of depression were recruited directly from the community via newspaper advertisements. Participants were remotely randomized to receive either immediate access (IA) or delayed access (DA) to a research version of the Living Life to the Full online CBT-based life skills package (3rd edition) with telephone support provided by nonspecialist, charity-based workers while they used the online intervention. The primary end point was at 3 months postrandomization, at which point, the DA group were offered the intervention. Levels of depression, anxiety, social functioning, and satisfaction were assessed. RESULTS: There were effective recruitment, randomization, and uptake, with 19 IA and 17 DA control participants entering the pilot study via newspaper advertisements and 13 of the 19 participants taking up the intervention. Overall, 72% (26/36) were not currently under the care of their general practitioner. The online package was acceptable to participants; the mean satisfaction score on the Client Satisfaction Questionnaire was 21 out of 32 (SD 8.89). At 3 months, data collection was achieved from 78% (28/36) of the participants. The efficacy and retention data were used for a power calculation indicating that 72 participants in total will be required for a future substantive RCT. CONCLUSIONS: The research design successfully tested the recruitment, data collection, and intervention delivery. The pilot study has provided data for the required sample size for the full RCT. TRIAL REGISTRATION: ISRCTN registry ISRCTN12890709; https://doi.org/10.1186/ISRCTN12890709. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-016-1336-y.

Adherence to prescribed medications in patients with heart failure: insights from liquid chromatography-tandem mass spectrometry-based urine analysis.

AIMS: None of the existing studies on adherence have directly measured levels of all medications (or their metabolites) in patients with heart failure (HF). METHODS AND RESULTS: We used liquid chromatography-tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4-6 weeks after hospitalization with HF. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent, i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only seven out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed HF drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients. CONCLUSION: Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in one of five patients evaluated 4-6 weeks after hospitalization with HF.

Measuring the effects of listening for leisure on outcome after stroke (MELLO): A pilot randomized controlled trial of mindful music listening.

BACKGROUND: Cognitive deficits and low mood are common post-stroke. Music listening is suggested to have beneficial effects on cognition, while mindfulness may improve mood. Combining these approaches may enhance cognitive recovery and improve mood early post-stroke. AIMS: To assess the feasibility and acceptability of a novel mindful music listening intervention. METHODS: A parallel group randomized controlled feasibility trial with ischemic stroke patients, comparing three groups; mindful music listening, music listening and audiobook listening (control group), eight weeks intervention. Feasibility was measured using adherence to protocol and questionnaires. Cognition (including measures of verbal memory and attention) and mood (Hospital Anxiety and Depression Scale) were assessed at baseline, end of intervention and at six-months post-stroke. RESULTS: Seventy-two participants were randomized to mindful music listening (n = 23), music listening (n = 24), or audiobook listening (n = 25). Feasibility and acceptability measures were encouraging: 94% fully consistent with protocol; 68.1% completing ≥6/8 treatment visits; 80-107% listening adherence; 83% retention to six-month endpoint. Treatment effect sizes for cognition at six month follow-up ranged from d = 0.00 ([-0.64,0.64], music alone), d = 0.31, ([0.36,0.97], mindful music) for list learning; to d = 0.58 ([0.06,1.11], music alone), d = 0.51 ([-0.07,1.09], mindful music) for immediate story recall; and d = 0.67 ([0.12,1.22], music alone), d = 0.77 ([0.16,1.38]mindful music) for attentional switching compared to audiobooks. No signal of change was seen for mood. A definitive study would require 306 participants to detect a clinically substantial difference in improvement (z-score difference = 0.66, p = 0.017, 80% power) in verbal memory (delayed story recall). CONCLUSIONS: Mindful music listening is feasible and acceptable post-stroke. Music listening interventions appear to be a promising approach to improving recovery from stroke.

Predictors of segmental myocardial functional recovery in patients after an acute ST-Elevation myocardial infarction.

OBJECTIVE: We hypothesized that Displacement Encoding with Stimulated Echoes (DENSE) and feature-tracking derived circumferential strain would provide incremental prognostic value over the extent of infarction for recovery of segmental myocardial function. METHODS: Two hundred and sixty-one patients (mean age 59 years, 73% male) underwent MRI 2 days post-ST elevation myocardial infarction (STEMI) and 241 (92%) underwent repeat imaging 6 months later. The MRI protocol included cine, 2D-cine DENSE, T2 mapping and late enhancement. Wall motion scoring was assessed by 2-blinded observers and adjudicated by a third. (WMS: 1=normal, 2=hypokinetic, 3=akinetic, 4=dyskinetic). WMS improvement was defined as a decrease in WMS ≥ 1, and normalization where WMS = 1 on follow-up. Segmental circumferential strain was derived utilizing DENSE and feature-tracking. A generalized linear mixed model with random effect of subject was constructed and used to account for repeated sampling when investigating predictors of segmental myocardial improvement or normalization RESULTS: At baseline and follow-up, 1416 segments had evaluable data for all parameters. Circumferential strain by DENSE (p < 0.001) and feature-tracking (p < 0.001), extent of oedema (p < 0.001), infarct size (p < 0.001), and microvascular obstruction (p < 0.001) were associates of both improvement and normalization of WMS. Circumferential strain provided incremental predictive value even after accounting for infarct size, extent of oedema and microvascular obstruction, for segmental improvement (DENSE: odds ratio, 95% confidence intervals: 1.08 per -1% peak strain, 1.05-1.12, p < 0.001, feature-tracking: odds ratio, 95% confidence intervals: 1.05 per -1% peak strain, 1.03-1.07, p < 0.001) and segmental normalization (DENSE: 1.08 per -1% peak strain, 1.04-1.12, p < 0.001, feature-tracking: 1.06 per -1% peak strain, 1.04-1.08, p < 0.001). CONCLUSIONS: Circumferential strain provides incremental prognostic value over segmental infarct size in patients post STEMI for predicting segmental improvement or normalization by wall-motion scoring.

Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights.

OBJECTIVES: The aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI). BACKGROUND: The pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood. METHODS: Patients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used. RESULTS: In total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post-percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99). CONCLUSIONS: Smoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850).

Statin Use is Not Associated with Future Long-Term Care Admission: Extended Follow-Up of Two Randomised Controlled Trials.

BACKGROUND: Statins have been associated with later life, long-term care admission in observational studies. However, by preventing vascular events, statins may also prevent or delay admission. We wished to determine statin and long-term care admission associations in a randomised controlled trial context, and describe associations between long-term care admission and other clinical and demographic factors. METHODS: We used extended follow-up of two randomised trial populations, using national data to assign the long-term care admission outcome, and included individuals screened or recruited to two large randomised trials of pravastatin 40 mg daily-the West of Scotland Coronary Prevention Study (WOSCOPS) and the pravastatin in elderly individuals at risk of vascular disease (PROSPER) study. We described univariable and multivariable analyses of potential predictors of long-term care admission with corresponding survival curves of incident long-term care admission and analyses adjusted for competing risk. RESULTS: In total 11,015 (10%) of the trial participants were admitted to long-term care. There was no difference between participants in the statin or placebo arms of either trial in regard to admissions to long-term care. On multivariable analyses, independent associations with incident long-term care admission in the PROSPER trial were age (hazard ratio [HR] 1.06 per year, 95% confidence interval [CI] 1.03-1.09) and male sex (HR 0.72, 95% CI 0.53-0.99). In the WOSCOPS, age (HR 1.12 per year, 95% CI 1.10-1.13) and increasing social deprivation (HR 1.05, 95% CI 1.03-1.08) were associated with incident long-term care admission. CONCLUSION: We did not demonstrate an association between historical statin use and future long-term care admission. The strongest associations with incident long-term care admission were non-modifiable factors of age, sex and socioeconomic deprivation.

Maternal thyroid function and child educational attainment: prospective cohort study.

OBJECTIVE: To determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment. DESIGN: Prospective cohort study. SETTING: Avon Longitudinal Study of Parents and Children cohort in the UK. PARTICIPANTS: 4615 mother-child pairs with an available first trimester sample (median 10 weeks gestation, interquartile range 8-12). EXPOSURES: Free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies assessed as continuous measures and the seven clinical categories of maternal thyroid function. MAIN OUTCOME MEASURES: Five age-specific national curriculum assessments in 3580 children at entry stage assessment at 54 months, increasing up to 4461 children at their final school assessment at age 15. RESULTS: No strong evidence of clinically meaningful associations of first trimester free thyroxine and thyroid stimulating hormone levels with entry stage assessment score or Standard Assessment Test scores at any of the key stages was found. Associations of maternal free thyroxine or thyroid stimulating hormone with the total number of General Certificates of Secondary Education (GCSEs) passed (range 0-16) were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed when more detailed capped scores of GCSEs allowing for both the number and grade of pass or when language, mathematics, and science performance were examined individually or when all educational assessments undertaken by an individual from school entry to leaving were considered. 200 (4.3%) mothers were newly identified as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction attained an equivalent number of GCSEs and equivalent grades as children of mothers with euthyroidism. CONCLUSIONS: Maternal thyroid dysfunction in early pregnancy does not have a clinically important association with impaired child performance at school or educational achievement.

Participants' experiences of music, mindful music, and audiobook listening interventions for people recovering from stroke.

Existing research evidence suggests that both music listening and mindfulness interventions may have beneficial effects on mood and cognition poststroke. This mixed-methods study, nested within a pilot randomized controlled trial investigating the feasibility and acceptability of combining music listening and brief mindfulness training poststroke, explored study participants' experiences of engaging in the interventions. Fifty-six stroke survivors who were randomized to receive an 8-week intervention of mindful music listening (n = 15), music listening (n = 21), or audiobook listening (n = 20, control) using self-selected material participated in a postintervention individual semistructured interview with a researcher not involved in their intervention delivery. Interview questions focused on affective, cognitive, and physical experiences. Data were coded and analyzed using thematic analysis. Across groups, listening was associated with positive distraction from thoughts and worries. Mindful music listening was most strongly associated with relaxation and concentration, improved attentional control, and emotion regulation, as well as enjoyment. Music listening was most strongly associated with increased activity, memory reminiscence, and improved mood. In addition, participants provided valuable feedback on intervention feasibility and acceptability. The findings suggest that the interventions were feasible and enjoyable for people recovering from stroke.