Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial.

BACKGROUND AND AIMS: Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear. METHODS: From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy. RESULTS: Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)]. CONCLUSIONS: Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.

An Automated, Online Feasibility Randomized Controlled Trial of a Just-In-Time Adaptive Intervention for Smoking Cessation (Quit Sense).

INTRODUCTION: Learned smoking cues from a smoker's environment are a major cause of lapse and relapse. Quit Sense, a theory-guided Just-In-Time Adaptive Intervention smartphone app, aims to help smokers learn about their situational smoking cues and provide in-the-moment support to help manage these when quitting. METHODS: A two-arm feasibility randomized controlled trial (N = 209) to estimate parameters to inform a definitive evaluation. Smoker's willing to make a quit attempt were recruited using online paid-for adverts and randomized to "usual care" (text message referral to NHS SmokeFree website) or "usual care" plus a text message invitation to install Quit Sense. Procedures, excluding manual follow-up for nonresponders, were automated. Follow-up at 6 weeks and 6 months included feasibility, intervention engagement, smoking-related, and economic outcomes. Abstinence was verified using cotinine assessment from posted saliva samples. RESULTS: Self-reported smoking outcome completion rates at 6 months were 77% (95% CI 71%, 82%), viable saliva sample return rate was 39% (95% CI 24%, 54%), and health economic data 70% (95% CI 64%, 77%). Among Quit Sense participants, 75% (95% CI 67%, 83%) installed the app and set a quit date and, of those, 51% engaged for more than one week. The 6-month biochemically verified sustained abstinence rate (anticipated primary outcome for definitive trial), was 11.5% (12/104) among Quit Sense participants and 2.9% (3/105) for usual care (adjusted odds ratio = 4.57, 95% CIs 1.23, 16.94). No evidence of between-group differences in hypothesized mechanisms of action was found. CONCLUSIONS: Evaluation feasibility was demonstrated alongside evidence supporting the effectiveness potential of Quit Sense. IMPLICATIONS: Running a primarily automated trial to initially evaluate Quit Sense was feasible, resulting in modest recruitment costs and researcher time, and high trial engagement. When invited, as part of trial participation, to install a smoking cessation app, most participants are likely to do so, and, for those using Quit Sense, an estimated one-half will engage with it for more than 1 week. Evidence that Quit Sense may increase verified abstinence at 6-month follow-up, relative to usual care, was generated, although low saliva return rates to verify smoking status contributed to considerable imprecision in the effect size estimate.

Association of Spontaneous and Induced Self-Affirmation With Smoking Cessation in Users of a Mobile App: Randomized Controlled Trial.

BACKGROUND: Most smokers attempt to stop using cigarettes numerous times before successfully quitting. Cigarette cravings may undermine perceived competence to quit and thus constitute psychological threats to the individual's self-concept. Self-affirmation may promote smoking cessation by offsetting these threats. OBJECTIVE: This study examines whether self-affirmation is associated with smoking cessation in the context of a cessation app. Two types of self-affirmation are examined: tendency to spontaneously self-affirm, and self-affirmation inductions added to a publicly available smoking cessation app (Smoke-Free Quit Smoking Now). In addition, this study explores whether optimism and emotional states (happiness, anger, anxiousness, hopefulness, sadness) predict smoking cessation. METHODS: All users who met the inclusion criteria, provided consent to participate, and completed a baseline assessment, including all individual difference measures, were randomized to 1 of 4 conditions. Half of the participants were randomly assigned to complete a self-affirmation induction upon study entry. Orthogonally, half of the participants were randomly assigned to receive self-affirming text notifications during their quit attempt or to receive conventional notifications. The induction and the text notifications were fully automated, and all data were collected through self-assessments in the app. Self-reported smoking cessation was assessed 1 month and 3 months following study entry. RESULTS: The study enrolled 7899 participants; 647 completed the 1-month follow-up. Using an intent-to-treat analysis at the 1-month follow-up, 7.2% (569/7899) of participants self-reported not smoking in the previous week and 6.4% (503/7899) self-reported not smoking in the previous month. Greater tendency to spontaneously self-affirm predicted a greater likelihood of cessation (P<.001) at 1 month after controlling for smoking-related variables. Neither self-affirmation induction influenced cessation. In addition, spontaneous self-affirmation did not moderate the relationship between self-affirmation inductions and cessation. Greater baseline sadness was associated with a lower likelihood of reporting successful cessation. Optimism predicted past-week cessation at the 1-month follow-up, and both happiness and anger predicted past-month cessation at the 1-month follow-up; however, none of these potential predictors moderated the relationship between self-affirmation conditions and successful cessation. CONCLUSIONS: Spontaneous self-affirmation may be an important psychological resource for managing threats to self-concept during the smoking cessation process. Sadness may hinder quit attempts. Future research can explicate how spontaneous versus induced self-affirmation can promote smoking cessation and examine boundary conditions for the effectiveness of disseminated self-affirmation interventions. TRIAL REGISTRATION: ISRCTN Registry 56646695; https://www.isrctn.com/ISRCTN56646695.

BOLD-based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease.

Cerebrovascular reactivity (CVR) is a dynamic measure of the cerebral blood vessel response to vasoactive stimulus. Conventional CVR measures amplitude changes in the blood-oxygenation-level-dependent (BOLD) signal per unit change in end-tidal CO2 (PET CO2 ), effectively discarding potential timing information. This study proposes a deconvolution procedure to characterize CVR responses based on a vascular transfer function (VTF) that separates amplitude and timing CVR effects. We implemented the CVR-VTF to primarily evaluate normal-appearing white matter (WM) responses in those with a range of small vessel disease. Comparisons between simulations of PET CO2 input models revealed that boxcar and ramp hypercapnia paradigms had the lowest relative deconvolution error. We used a T2 * BOLD-MRI sequence on a 3 T MRI scanner, with a boxcar delivery model of CO2 , to test the CVR-VTF approach in 18 healthy adults and three white matter hyperintensity (WMH) groups: 20 adults with moderate WMH, 12 adults with severe WMH, and 10 adults with genetic WMH (CADASIL). A subset of participants performed a second CVR session at a one-year follow-up. Conventional CVR, area under the curve of VTF (VTF-AUC), and VTF time-to-peak (VTF-TTP) were assessed in WM and grey matter (GM) at baseline and one-year follow-up. WMH groups had lower WM VTF-AUC compared with the healthy group (p < 0.0001), whereas GM CVR did not differ between groups (p > 0.1). WM VTF-TTP of the healthy group was less than that in the moderate WMH group (p = 0.016). Baseline VTF-AUC was lower than follow-up VTF-AUC in WM (p = 0.013) and GM (p = 0.026). The intraclass correlation for VTF-AUC in WM was 0.39 and coefficient of repeatability was 0.08 [%BOLD/mm Hg]. This study assessed CVR timing and amplitude information without applying model assumptions to the CVR response; this approach may be useful in the development of robust clinical biomarkers of CSVD.

Behavior Change Techniques Used in Digital Behavior Change Interventions to Reduce Excessive Alcohol Consumption: A Meta-regression.

Background: Digital behavior change interventions (DBCIs) appear to reduce alcohol consumption, but greater understanding is needed of their mechanisms of action. Purpose: To describe the behavior change techniques (BCTs) used in DBCIs and examine whether individual BCTs, the inclusion of more BCTs or more Control Theory congruent BCTs is associated with increased effectiveness. Methods: Forty-one randomized control trials were extracted from a Cochrane review of alcohol reduction DBCIs and coded for up to 93 BCTs using an established and reliable method. Random effects unadjusted and adjusted meta-regression models were performed to assess associations between BCTs and intervention effectiveness. Results: Interventions used a mean of 9.1 BCTs (range 1-22), 23 different BCTs were used in four or more trials. Trials that used "Behavior substitution" (-95.112 grams per week [gpw], 95% CI: -162.90, -27.34), "Problem solving" (-45.92 gpw, 95% CI: -90.97, -0.87) and "Credible source" (-32.09 gpw, 95% CI: -60.64, -3.55) were significantly associated with greater alcohol reduction than trials without these BCTs. The "Behavior substitution" result should be treated as preliminary because it was reported in only four trials, three of which were conducted by the same research group. "Feedback" was used in 98% of trials (n = 41); other Control Theory congruent BCTs were used less frequently: for example, "Goal setting" 43% (n = 18) and "Self-monitoring" 29%, (n = 12). Conclusions: "Behavior substitution," "Problem solving," and "Credible source" were associated with greater alcohol reduction. Many BCTs were used infrequently in DBCIs, including BCTs with evidence of effectiveness in other domains, such as "Self-monitoring" and "Goal setting."

Reported Theory Use by Digital Interventions for Hazardous and Harmful Alcohol Consumption, and Association With Effectiveness: Meta-Regression.

BACKGROUND: Applying theory to the design and evaluation of interventions is likely to increase effectiveness and improve the evidence base from which future interventions are developed, though few interventions report this. OBJECTIVE: The aim of this paper was to assess how digital interventions to reduce hazardous and harmful alcohol consumption report the use of theory in their development and evaluation, and whether reporting of theory use is associated with intervention effectiveness. METHODS: Randomized controlled trials were extracted from a Cochrane review on digital interventions for reducing hazardous and harmful alcohol consumption. Reporting of theory use within these digital interventions was investigated using the theory coding scheme (TCS). Reported theory use was analyzed by frequency counts and descriptive statistics. Associations were analyzed with meta-regression models. RESULTS: Of 41 trials involving 42 comparisons, half did not mention theory (50% [21/42]), and only 38% (16/42) used theory to select or develop the intervention techniques. Significant heterogeneity existed between studies in the effect of interventions on alcohol reduction (I2=77.6%, P<.001). No significant associations were detected between reporting of theory use and intervention effectiveness in unadjusted models, though the meta-regression was underpowered to detect modest associations. CONCLUSIONS: Digital interventions offer a unique opportunity to refine and develop new dynamic, temporally sensitive theories, yet none of the studies reported refining or developing theory. Clearer selection, application, and reporting of theory use is needed to accurately assess how useful theory is in this field and to advance the field of behavior change theories.

Personalised digital interventions for reducing hazardous and harmful alcohol consumption in community-dwelling populations.

BACKGROUND: Excessive alcohol use contributes significantly to physical and psychological illness, injury and death, and a wide array of social harm in all age groups. A proven strategy for reducing excessive alcohol consumption levels is to offer a brief conversation-based intervention in primary care settings, but more recent technological innovations have enabled people to interact directly via computer, mobile device or smartphone with digital interventions designed to address problem alcohol consumption. OBJECTIVES: To assess the effectiveness and cost-effectiveness of digital interventions for reducing hazardous and harmful alcohol consumption, alcohol-related problems, or both, in people living in the community, specifically: (i) Are digital interventions more effective and cost-effective than no intervention (or minimal input) controls? (ii) Are digital interventions at least equally effective as face-to-face brief alcohol interventions? (iii) What are the effective component behaviour change techniques (BCTs) of such interventions and their mechanisms of action? (iv) What theories or models have been used in the development and/or evaluation of the intervention? Secondary objectives were (i) to assess whether outcomes differ between trials where the digital intervention targets participants attending health, social care, education or other community-based settings and those where it is offered remotely via the internet or mobile phone platforms; (ii) to specify interventions according to their mode of delivery (e.g. functionality features) and assess the impact of mode of delivery on outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, ERIC, HTA and Web of Knowledge databases; ClinicalTrials.com and WHO ICTRP trials registers and relevant websites to April 2017. We also checked the reference lists of included trials and relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effectiveness of digital interventions compared with no intervention or with face-to-face interventions for reducing hazardous or harmful alcohol consumption in people living in the community and reported a measure of alcohol consumption. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 57 studies which randomised a total of 34,390 participants. The main sources of bias were from attrition and participant blinding (36% and 21% of studies respectively, high risk of bias). Forty one studies (42 comparisons, 19,241 participants) provided data for the primary meta-analysis, which demonstrated that participants using a digital intervention drank approximately 23 g alcohol weekly (95% CI 15 to 30) (about 3 UK units) less than participants who received no or minimal interventions at end of follow up (moderate-quality evidence).Fifteen studies (16 comparisons, 10,862 participants) demonstrated that participants who engaged with digital interventions had less than one drinking day per month fewer than no intervention controls (moderate-quality evidence), 15 studies (3587 participants) showed about one binge drinking session less per month in the intervention group compared to no intervention controls (moderate-quality evidence), and in 15 studies (9791 participants) intervention participants drank one unit per occasion less than no intervention control participants (moderate-quality evidence).Only five small studies (390 participants) compared digital and face-to-face interventions. There was no difference in alcohol consumption at end of follow up (MD 0.52 g/week, 95% CI -24.59 to 25.63; low-quality evidence). Thus, digital alcohol interventions produced broadly similar outcomes in these studies. No studies reported whether any adverse effects resulted from the interventions.A median of nine BCTs were used in experimental arms (range = 1 to 22). 'B' is an estimate of effect (MD in quantity of drinking, expressed in g/week) per unit increase in the BCT, and is a way to report whether individual BCTs are linked to the effect of the intervention. The BCTs of goal setting (B -43.94, 95% CI -78.59 to -9.30), problem solving (B -48.03, 95% CI -77.79 to -18.27), information about antecedents (B -74.20, 95% CI -117.72 to -30.68), behaviour substitution (B -123.71, 95% CI -184.63 to -62.80) and credible source (B -39.89, 95% CI -72.66 to -7.11) were significantly associated with reduced alcohol consumption in unadjusted models. In a multivariable model that included BCTs with B > 23 in the unadjusted model, the BCTs of behaviour substitution (B -95.12, 95% CI -162.90 to -27.34), problem solving (B -45.92, 95% CI -90.97 to -0.87), and credible source (B -32.09, 95% CI -60.64 to -3.55) were associated with reduced alcohol consumption.The most frequently mentioned theories or models in the included studies were Motivational Interviewing Theory (7/20), Transtheoretical Model (6/20) and Social Norms Theory (6/20). Over half of the interventions (n = 21, 51%) made no mention of theory. Only two studies used theory to select participants or tailor the intervention. There was no evidence of an association between reporting theory use and intervention effectiveness. AUTHORS' CONCLUSIONS: There is moderate-quality evidence that digital interventions may lower alcohol consumption, with an average reduction of up to three (UK) standard drinks per week compared to control participants. Substantial heterogeneity and risk of performance and publication bias may mean the reduction was lower. Low-quality evidence from fewer studies suggested there may be little or no difference in impact on alcohol consumption between digital and face-to-face interventions.The BCTs of behaviour substitution, problem solving and credible source were associated with the effectiveness of digital interventions to reduce alcohol consumption and warrant further investigation in an experimental context.Reporting of theory use was very limited and often unclear when present. Over half of the interventions made no reference to any theories. Limited reporting of theory use was unrelated to heterogeneity in intervention effectiveness.

Multisite evaluations of a T2 -relaxation-under-spin-tagging (TRUST) MRI technique to measure brain oxygenation.

PURPOSE: Venous oxygenation (Yv ) is an important index of brain physiology and may be indicative of brain diseases. A T2 -relaxation-under-spin-tagging (TRUST) MRI technique was recently developed to measure Yv . A multisite evaluation of this technique would be an important step toward broader availability and potential clinical utilizations of Yv measures. METHODS: TRUST MRI was performed on a total of 250 healthy subjects, 125 from the developer's site and 25 each from five other sites. All sites were equipped with a 3 Tesla (T) MRI of the same vendor. The estimated Yv and the standard error (SE) of the estimation εYv were compared across sites. RESULTS: The averaged Yv and εYv across six sites were 61.1% ± 1.4% and 1.3% ± 0.2%, respectively. Multivariate regression analysis showed that the estimated Yv was dependent on age (P = 0.009) but not on performance site. In contrast, the SE of the Yv estimation was site-dependent (P = 0.024) but was less than 1.5%. Further analysis revealed that εYv was positively associated with the amount of subject motion (P < 0.001) but negatively associated with blood signal intensity (P < 0.001). CONCLUSION: This work suggests that TRUST MRI can yield equivalent results of Yv estimation across different sites.

Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients.

PURPOSE: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. METHODS: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. RESULTS: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. CONCLUSION: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.

Evaluating the effectiveness of a smartphone app to reduce excessive alcohol consumption: protocol for a factorial randomised control trial.

BACKGROUND: Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed. Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol. However, there has been little evaluation of the effectiveness of existing smartphone interventions. A systematic review, amongst other methodologies, identified promising modular content that could be delivered by an app: self-monitoring and feedback; action planning; normative feedback; cognitive bias re-training; and identity change. This protocol reports a factorial randomised controlled trial to assess the comparative potential of these five intervention modules to reduce excessive alcohol consumption. METHODS: A between-subject factorial randomised controlled trial. Hazardous and harmful drinkers aged 18 or over who are making a serious attempt to reduce their drinking will be randomised to one of 32 (2(5)) experimental conditions after downloading the 'Drink Less' app. Participants complete baseline measures on downloading the app and are contacted after 1-month with a follow-up questionnaire. The primary outcome measure is change in past week consumption of alcohol. Secondary outcome measures are change in AUDIT score, app usage data and usability ratings for the app. A factorial between-subjects ANOVA will be conducted to assess main and interactive effects of the five intervention modules for the primary and secondary outcome measures. DISCUSSION: This study will establish the extent to which the five intervention modules offered in this app can help reduce hazardous and harmful drinking. This is the first step in optimising and understanding what component parts of an app could help to reduce excessive alcohol consumption. The findings from this study will be used to inform the content of a future integrated treatment app and evaluated against a minimal control in a definitive randomised control trial with long-term outcomes. TRIAL REGISTRATION: ISRCTN40104069 Date of registration: 10/2/2016.

Vascular risk factor burden correlates with cerebrovascular reactivity but not resting state coactivation in the default mode network.

PURPOSE: White matter hyperintensities (WMH) are prevalent among older adults and are often associated with cognitive decline and increased risk of stroke and dementia. Vascular risk factors (VRFs) are linked to WMH, yet the impact of multiple VRFs on gray matter function is still unclear. The goal of this study was to test for associations between the number of VRFs and cerebrovascular reactivity (CVR) and resting state (RS) coactivation among individuals with WMH. MATERIALS AND METHODS: Twenty-nine participants with suspected WMH were grouped based on the number of VRFs (subgroups: 0, 1, or ≥2). CVR and RS coactivation were measured with blood oxygenation level-dependent (BOLD) imaging on a 3T magnetic resonance imaging (MRI) system during hypercapnia and rest, respectively. Default-mode (DMN), sensory-motor, and medial-visual networks, generated using independent component analysis of RS-BOLD, were selected as networks of interest (NOIs). CVR-BOLD was analyzed using two methods: 1) a model-based approach using CO2 traces, and 2) a dual-regression (DR) approach using NOIs as spatial inputs. Average CVR and RS coactivations within NOIs were compared between VRF subgroups. A secondary analysis investigated the correlation between CVR and RS coactivation. RESULTS: VRF subgroup differences were detected using DR-based CVR in the DMN (F20,2 = 5.17, P = 0.015) but not the model-based CVR nor RS coactivation. DR-based CVR was correlated with RS coactivation in the DMN (r(2) = 0.28, P = 0.006) but not the sensory-motor nor medial-visual NOIs. CONCLUSION: In individuals with WMH, CVR in the DMN was inversely associated with the number of VRFs and correlated with RS coactivation.

Automated removal of spurious intermediate cerebral blood flow volumes improves image quality among older patients: A clinical arterial spin labeling investigation.

PURPOSE: To evaluate the impact of rejecting intermediate cerebral blood flow (CBF) images that are adversely affected by head motion during an arterial spin labeling (ASL) acquisition. MATERIALS AND METHODS: Eighty participants were recruited, representing a wide age range (14-90 years) and heterogeneous cerebrovascular health conditions including bipolar disorder, chronic stroke, and moderate to severe white matter hyperintensities of presumed vascular origin. Pseudocontinuous ASL and T1 -weigthed anatomical images were acquired on a 3T scanner. ASL intermediate CBF images were included based on their contribution to the mean estimate, with the goal to maximize CBF detectability in gray matter (GM). Simulations were conducted to evaluate the performance of the proposed optimization procedure relative to other ASL postprocessing approaches. Clinical CBF images were also assessed visually by two experienced neuroradiologists. RESULTS: Optimized CBF images (CBFopt ) had significantly greater agreement with a synthetic ground truth CBF image and greater CBF detectability relative to the other ASL analysis methods (P < 0.05). Moreover, empirical CBFopt images showed a significantly improved signal-to-noise ratio relative to CBF images obtained from other postprocessing approaches (mean: 12.6%; range 1% to 56%; P < 0.001), and this improvement was age-dependent (P = 0.03). Differences between CBF images from different analysis procedures were not perceptible by visual inspection, while there was a moderate agreement between the ratings (κ = 0.44, P < 0.001). CONCLUSION: This study developed an automated head motion threshold-free procedure to improve the detection of CBF in GM. The improvement in CBF image quality was larger when considering older participants.

Exercise intensity modulates the change in cerebral blood flow following aerobic exercise in chronic stroke.

The mechanisms supporting functional improvement by aerobic exercise following stroke remain incompletely understood. This study investigated how cycling intensity and aerobic fitness influence cerebral blood flow (CBF) following a single exercise session. Thirteen community-living stroke survivors performed 20 min of semi-recumbent cycling at low and moderate intensities (40-50 and 60-70 % of heart rate reserve, respectively) as determined from an exercise stress test. CBF was quantified by arterial spin labeling MRI at baseline, as well as 30 and 50 min post-exercise. An intensity-dependent effect was observed in the right post-central and supramarginal gyri up to 50 min after exercise (uncorrected p < 0.005, cluster size ≥10). Regional CBF was increased 18 ± 17 % and reduced 8 ± 12 % following moderate- and low-intensity cycling, respectively. In contrast, CBF changes were similar between sessions in the right lentiform nucleus and mid-frontal gyrus, as well as the left temporal and parietal gyri. Aerobic fitness was directly related to posterior cingulate and thalamic CBF, and inversely related to precuneal CBF at rest (R (2) ≥ 0.75); however, no relationship between fitness and the post-exercise change in CBF was observed. Divergent changes in regional CBF were observed in the right parietal cortex following low- and moderate-intensity exercise, which suggests that intensity of prescribed exercise may be useful in optimizing rehabilitation.

Declines in polybrominated diphenyl ether contamination of San Francisco Bay following production phase-outs and bans.

California has implemented unique consumer product flammability standards. Polybrominated diphenyl ether (PBDE) flame retardants were once widely incorporated into products to meet these standards, but concerns regarding toxicity and accumulation in humans and biota led to nationwide phase-outs and state bans. A decade of PBDE monitoring in San Francisco Bay has resulted in a data set that covers periods during and after PBDE use and consists of hundreds of measurements of water, sediment, and biota. While PBDEs remain widely detected in biota, levels have declined by nearly half in sport fish and 74-95% in bivalves and bird eggs. Concentrations of BDE-47 in sediment have dropped by over one-third from 2002 to 2012; in water, a decline is not yet evident. The dominant congener in sediment, DecaBDE component BDE-209, showed no temporal trend. U.S. production of DecaBDE ended in 2013; future monitoring may reveal declines. Overall, the data indicate that reduced production can result in relatively rapid reductions in the concentrations of some hydrophobic contaminants in biota and sediment, particularly when implemented after only a few decades of heavy use. Recent changes to California's flammability standards may lessen the use of other flame retardants and similarly reduce Bay contamination.

Behavior change techniques in popular alcohol reduction apps: content analysis.

BACKGROUND: Mobile phone apps have the potential to reduce excessive alcohol consumption cost-effectively. Although hundreds of alcohol-related apps are available, there is little information about the behavior change techniques (BCTs) they contain, or the extent to which they are based on evidence or theory and how this relates to their popularity and user ratings. OBJECTIVE: Our aim was to assess the proportion of popular alcohol-related apps available in the United Kingdom that focus on alcohol reduction, identify the BCTs they contain, and explore whether BCTs or the mention of theory or evidence is associated with app popularity and user ratings. METHODS: We searched the iTunes and Google Play stores with the terms "alcohol" and "drink", and the first 800 results were classified into alcohol reduction, entertainment, or blood alcohol content measurement. Of those classified as alcohol reduction, all free apps and the top 10 paid apps were coded for BCTs and for reference to evidence or theory. Measures of popularity and user ratings were extracted. RESULTS: Of the 800 apps identified, 662 were unique. Of these, 13.7% (91/662) were classified as alcohol reduction (95% CI 11.3-16.6), 53.9% (357/662) entertainment (95% CI 50.1-57.7), 18.9% (125/662) blood alcohol content measurement (95% CI 16.1-22.0) and 13.4% (89/662) other (95% CI 11.1-16.3). The 51 free alcohol reduction apps and the top 10 paid apps contained a mean of 3.6 BCTs (SD 3.4), with approximately 12% (7/61) not including any BCTs. The BCTs used most often were "facilitate self-recording" (54%, 33/61), "provide information on consequences of excessive alcohol use and drinking cessation" (43%, 26/61), "provide feedback on performance" (41%, 25/61), "give options for additional and later support" (25%, 15/61) and "offer/direct towards appropriate written materials" (23%, 14/61). These apps also rarely included any of the 22 BCTs frequently used in other health behavior change interventions (mean 2.46, SD 2.06). Evidence was mentioned by 16.4% of apps, and theory was not mentioned by any app. Multivariable regression showed that apps including advice on environmental restructuring were associated with lower user ratings (Β=-46.61, P=.04, 95% CI -91.77 to -1.45) and that both the techniques of "advise on/facilitate the use of social support" (Β=2549.21, P=.04, 95% CI 96.75-5001.67) and the mention of evidence (Β=1376.74, P=.02, 95%, CI 208.62-2544.86) were associated with the popularity of the app. CONCLUSIONS: Only a minority of alcohol-related apps promoted health while the majority implicitly or explicitly promoted the use of alcohol. Alcohol-related apps that promoted health contained few BCTs and none referred to theory. The mention of evidence was associated with more popular apps, but popularity and user ratings were only weakly associated with the BCT content.

Modeling and correction of bolus dispersion effects in dynamic susceptibility contrast MRI.

PURPOSE: Bolus dispersion in DSC-MRI can lead to errors in cerebral blood flow (CBF) estimation by up to 70% when using singular value decomposition analysis. However, it might be possible to correct for dispersion using two alternative methods: the vascular model (VM) and control point interpolation (CPI). Additionally, these approaches potentially provide a means to quantify the microvascular residue function. METHODS: VM and CPI were extended to correct for dispersion by means of a vascular transport function. Simulations were performed at multiple dispersion levels and an in vivo analysis was performed on a healthy subject and two patients with carotid atherosclerotic disease. RESULTS: Simulations showed that methods that could not address dispersion tended to underestimate CBF (ratio in CBF estimation, CBFratio = 0.57-0.77) in the presence of dispersion; whereas modified CPI showed the best performance at low-to-medium dispersion; CBFratio = 0.99 and 0.81, respectively. The in vivo data showed trends in CBF estimation and residue function that were consistent with the predictions from simulations. CONCLUSION: In patients with atherosclerotic disease the estimated residue function showed considerable differences in the ipsilateral hemisphere. These differences could partly be attributed to dispersive effects arising from the stenosis when dispersion corrected CPI was used. It is thus beneficial to correct for dispersion in perfusion analysis using this method.

Modeling the residue function in DSC-MRI simulations: analytical approximation to in vivo data.

PURPOSE: An exponential residue function is commonly used in numerical simulations to assess the accuracy of perfusion quantification using dynamic susceptibility contrast (DSC) MRI. Although this might be a reasonable assumption for normal tissue, microvascular hemodynamics are likely to be significantly altered in pathology. Thus the exponential function may no longer be appropriate and the estimated accuracy of DSC-MRI quantification might be inappropriate. The purpose of this study was to characterize in vivo residue function variations in normal and infarcted tissue in a chronic atherosclerotic disease cohort, and to find the most appropriate model for use in DSC simulations. METHODS: Residue functions were measured in vivo in patients with atherosclerotic disease using a nonparametric Control Point Interpolation method, which has been shown to provide a robust characterization of the shape of the residue function. The observed residue functions were approximated with five commonly used analytical expressions: exponential, bi-exponential, Lorentzian, and Fermi functions, and a previously proposed Vascular Model. RESULTS: The lowest error was found with the bi-exponential function approximations to the in vivo residue functions from both normal and infarcted tissue. CONCLUSION: A bi-exponential model should therefore be used in future numerical simulations of DSC-MRI instead of the exponential function.

Modulation of the default-mode network between rest and task in Alzheimer's Disease.

Default-mode network (DMN) connectivity at rest is disrupted in Alzheimer's Disease (AD), but it is unknown whether this abnormality is a static feature, or if it varies across cognitive states. We measured DMN integrity in 16 patients with mild AD and 18 controls during resting state and a simple visual task. Patients showed resting-state deficits in the parahippocampal gyrus and posterior cingulate. No group differences were found during the task. Controls exhibited higher DMN connectivity of multiple regions during rest than task, while the patient group showed no modulation of the DMN between states. However, the relative degree of increased resting- versus task-state co-activation in the posterior cingulate and precuneus was predictive of mini-mental status exam (MMSE) scores in AD patients, while measures at rest or task alone were not associated with MMSE. These findings suggest that a resting state may be more suited to detecting DMN abnormalities in AD than a simple task. However, the degree of state-dependent modulation in the DMN may be a better predictor of the individual cognitive status than a single-state acquisition. This study demonstrates an apparent reduction in the capacity for DMN modulation in individuals with mild AD, the degree of which uniquely predicted cognitive status.

Treating Tobacco Dependency in National Health Service Workers in Greater Manchester: An Evaluation of a Bespoke Digital Service.

Introduction: Treating tobacco dependency in National Health Service (NHS) workers delivers substantial benefits at an individual, population, and health care system level. We report the outcomes from the Greater Manchester Integrated Care Partnership's tobacco dependency treatment program for NHS workers which includes 6-months' access to behavioral support and 12 weeks of treatment through a digital application. Methods: Aggregate results for all participants across the program from January 1, 2022, to September 1, 2023, are reported including a deep-dive evaluation of 300 participants recruited to provide chemically validated outcomes. Results: A total of 1567 NHS workers participated in the program within the evaluation period, completing 24,048 sessions with specialist advisors within the application, ordering 18,710 nicotine vape liquids, 6927 nicotine patches, and 297 short-acting nicotine products. Users reported achieving 89,464 smoke-free days, 1,258,069 less cigarettes smoked, and a financial saving of £622,231. The deep-dive evaluation revealed a CO-verified 12-week abstinence rate of 37% (111 of 300). Conclusion: This evaluation provides assurance of clinical effectiveness within a bespoke digital tobacco dependency treatment program for NHS workers across an Integrated Care Partnership.

A smoking cessation smartphone app that delivers real-time 'context aware' behavioural support: the Quit Sense feasibility RCT.

Background: During a quit attempt, cues from a smoker's environment are a major cause of brief smoking lapses, which increase the risk of relapse. Quit Sense is a theory-guided Just-In-Time Adaptive Intervention smartphone app, providing smokers with the means to learn about their environmental smoking cues and provides 'in the moment' support to help them manage these during a quit attempt. Objective: To undertake a feasibility randomised controlled trial to estimate key parameters to inform a definitive randomised controlled trial of Quit Sense. Design: A parallel, two-arm randomised controlled trial with a qualitative process evaluation and a 'Study Within A Trial' evaluating incentives on attrition. The research team were blind to allocation except for the study statistician, database developers and lead researcher. Participants were not blind to allocation. Setting: Online with recruitment, enrolment, randomisation and data collection (excluding manual telephone follow-up) automated through the study website. Participants: Smokers (323 screened, 297 eligible, 209 enrolled) recruited via online adverts on Google search, Facebook and Instagram. Interventions: Participants were allocated to 'usual care' arm (n = 105; text message referral to the National Health Service SmokeFree website) or 'usual care' plus Quit Sense (n = 104), via a text message invitation to install the Quit Sense app. Main outcome measures: Follow-up at 6 weeks and 6 months post enrolment was undertaken by automated text messages with an online questionnaire link and, for non-responders, by telephone. Definitive trial progression criteria were met if a priori thresholds were included in or lower than the 95% confidence interval of the estimate. Measures included health economic and outcome data completion rates (progression criterion #1 threshold: ≥ 70%), including biochemical validation rates (progression criterion #2 threshold: ≥ 70%), recruitment costs, app installation (progression criterion #3 threshold: ≥ 70%) and engagement rates (progression criterion #4 threshold: ≥ 60%), biochemically verified 6-month abstinence and hypothesised mechanisms of action and participant views of the app (qualitative). Results: Self-reported smoking outcome completion rates were 77% (95% confidence interval 71% to 82%) and health economic data (resource use and quality of life) 70% (95% CI 64% to 77%) at 6 months. Return rate of viable saliva samples for abstinence verification was 39% (95% CI 24% to 54%). The per-participant recruitment cost was £19.20, which included advert (£5.82) and running costs (£13.38). In the Quit Sense arm, 75% (95% CI 67% to 83%; 78/104) installed the app and, of these, 100% set a quit date within the app and 51% engaged with it for more than 1 week. The rate of 6-month biochemically verified sustained abstinence, which we anticipated would be used as a primary outcome in a future study, was 11.5% (12/104) in the Quit Sense arm and 2.9% (3/105) in the usual care arm (estimated effect size: adjusted odds ratio = 4.57, 95% CIs 1.23 to 16.94). There was no evidence of between-arm differences in hypothesised mechanisms of action. Three out of four progression criteria were met. The Study Within A Trial analysis found a £20 versus £10 incentive did not significantly increase follow-up rates though reduced the need for manual follow-up and increased response speed. The process evaluation identified several potential pathways to abstinence for Quit Sense, factors which led to disengagement with the app, and app improvement suggestions. Limitations: Biochemical validation rates were lower than anticipated and imbalanced between arms. COVID-19-related restrictions likely limited opportunities for Quit Sense to provide location tailored support. Conclusions: The trial design and procedures demonstrated feasibility and evidence was generated supporting the efficacy potential of Quit Sense. Future work: Progression to a definitive trial is warranted providing improved biochemical validation rates. Trial registration: This trial is registered as ISRCTN12326962. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 17/92/31) and is published in full in Public Health Research; Vol. 12, No. 4. See the NIHR Funding and Awards website for further award information.

Smokers often fail to quit because of urges to smoke triggered by their surroundings (e.g. being around smokers). We developed a smartphone app ('Quit Sense') which learns about an individual's surroundings and locations where they smoke. During a quit attempt, Quit Sense uses in-built sensors to identify when smokers are in those locations and sends 'in the moment' advice to help prevent them from smoking. We ran a feasibility study to help plan for a future large study to see if Quit Sense helps smokers to quit. This feasibility study was designed to tell us how many participants complete study measures; recruitment costs; how many participants install and use Quit Sense; and estimate whether Quit Sense may help smokers to stop and how it might do this. We recruited 209 smokers using online adverts on Google search, Facebook and Instagram, costing £19 per participant. Participants then had an equal chance of receiving a web link to the National Health Service SmokeFree website ('usual care group') or receive that same web link plus a link to the Quit Sense app ('Quit Sense group'). Three-quarters of the Quit Sense group installed the app on their phone and half of these used the app for more than 1 week. We followed up 77% of participants at 6 months to collect study data, though only 39% of quitters returned a saliva sample for abstinence verification. At 6 months, more people in the Quit Sense group had stopped smoking (12%) than the usual care group (3%). It was not clear how the app helped smokers to quit based on study measures, though interviews found that the process of training the app helped people quit through learning about what triggered their smoking behaviour. The findings support undertaking a large study to tell us whether Quit Sense really does help smokers to quit.