A noncanonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML.

RNA-binding proteins (RBPs) form a large and diverse class of factors, many members of which are overexpressed in hematologic malignancies. RBPs participate in various processes of messenger RNA (mRNA) metabolism and prevent harmful DNA:RNA hybrids or R-loops. Here, we report that PIWIL4, a germ stem cell-associated RBP belonging to the RNase H-like superfamily, is overexpressed in patients with acute myeloid leukemia (AML) and is essential for leukemic stem cell function and AML growth, but dispensable for healthy human hematopoietic stem cells. In AML cells, PIWIL4 binds to a small number of known piwi-interacting RNA. Instead, it largely interacts with mRNA annotated to protein-coding genic regions and enhancers that are enriched for genes associated with cancer and human myeloid progenitor gene signatures. PIWIL4 depletion in AML cells downregulates the human myeloid progenitor signature and leukemia stem cell (LSC)-associated genes and upregulates DNA damage signaling. We demonstrate that PIWIL4 is an R-loop resolving enzyme that prevents R-loop accumulation on a subset of AML and LSC-associated genes and maintains their expression. It also prevents DNA damage, replication stress, and activation of the ATR pathway in AML cells. PIWIL4 depletion potentiates sensitivity to pharmacological inhibition of the ATR pathway and creates a pharmacologically actionable dependency in AML cells.

Estimation of HbA1c after weight loss using a beta-regression for an economic evaluation of a behavioural weight management programme from the GLoW trial: a methodological study.

BACKGROUND: In economic evaluations, average intervention effects are usually applied to a population. However, this fails to reflect the change in the distribution of HbA1c due to heterogeneous responses to weight loss. We aimed to investigate whether allowing heterogeneous treatment effects using a beta regression better represented the distribution of HbA1c after a weight-loss intervention, and how this affected cost effectiveness. METHODS: The Glucose Lowering through Weight Management (GLoW) trial evaluated the effectiveness of a diabetes education and weight-loss intervention against a standard diabetes education programme. Adults diagnosed with type 2 diabetes within 3 years were recruited from Clinical Commissioning Groups across 159 sites in England from July 20, 2018, to July 22, 2018. Ethics approval (18/ES/0048) and participant informed consent were obtained. Considering the between-treatment-arm difference in HbA1c after 12 months, we compared a mean-effect estimated from a mixed-effects regression to a heterogeneous effect estimated from a beta regression performed on 12-month HbA1c conditional on baseline HbA1c, gender, diabetes duration and intervention group. We used the School of Public Health Research (SPHR) Diabetes Treatment model to apply these treatment effects and evaluate the lifetime NHS costs and quality-adjusted life-years (QALYs), discounted at 3·5%. The microsimulation model estimated diabetes-related health outcomes using the UK Prospective Diabetes Study Outcomes Model 2 risk equations and risk factor trajectory equations, alongside estimating diabetes remission, osteoarthritis, and cancer. We calculated the incremental net benefit (INB) of the intervention using a £20 000 per QALY valuation, by deterministic analysis. The GLoW trial is registered with the ISRCTN Registry, ISRCTN18399564. FINDINGS: The trial recruited 577 participants (mean age 60 years; 278 [53%] female, 247 [47%] male; 474 [91%] white ethnic background). Applying heterogeneous HbA1c changes better reproduced the skewness in post-intervention HbA1c than applying a mean-effect (Kolmogorov-Smirnov test p=0·02 compared with p=0·0000007). The beta-regression method suggested the intervention was more cost-effective, estimating an INB of £736 per person, compared with £584 when applying the mean-effect. INTERPRETATION: Alternative regression specification methods should be considered when evaluating the cost-effectiveness of interventions if the key intervention outcomes are not normally distributed. However, this alternative method requires further investigation to conclude its appropriateness in evaluating cost-effectiveness in different contexts. FUNDING: National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (Reference Number RP-PG0216-20010).

Magnetic Resonance-Guided Focused Ultrasound without Anesthesiologist Support.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) is an effective treatment option for essential tremor (ET) and tremor dominant Parkinson's disease (TDPD), which is often performed with sedation or in the presence of an anesthesiologist in an effort to minimize adverse events and maximize patient comfort. This study explores the safety, feasibility, and tolerability of performing MRgFUS without an anesthesiologist. METHODS: This is a single academic center, retrospective review of 180 ET and TDPD patients who underwent MRgFUS treatment without anesthesiologist support. Patient demographics, intra-procedural treatment parameters, peri-procedural adverse events, and 3-month Clinical Rating Scale for Tremor Part B (CRST-B) scores were compared to MRgFUS studies that utilized varying degrees of anesthesia. RESULTS: There were no anesthesia related adverse events or unsuccessful treatments. There were no early treatment terminations due to patient discomfort, regardless of skull density ratio. 94.6% of patients would repeat the procedure again. The most common side effects during treatment were facial/tongue paresthesia (26.3%), followed by nausea (22.3%), dysarthria (8.6%), and scalp pain (8.0%). No anxiolytic, pain, or antihypertensive medications were administered. The most common early adverse event after MRgFUS procedure was gait imbalance (58.3%). There was a significant reduction of 83.1% (83.4% ET and 80.5% TDPD) of the mean CRST-B scores of the treated hand when comparing 3-month and baseline scores (1.8 vs. 10.9, n = 109, p < 0.0001). CONCLUSION: MRgFUS without intra-procedural anesthesiologist support is a safe, feasible, and well-tolerated option, without an increase in peri-procedural adverse events.

Comparative analysis of hypoxic response of human microvascular and umbilical vein endothelial cells in 2D and 3D cell culture systems.

In vitro cultivation conditions play a crucial role in cell physiology and the cellular response to external stimuli. Oxygen concentrations represent an essential microenvironmental factor influencing cell physiology and behaviour both in vivo and in vitro. Therefore, new approaches are urgently needed to monitor and control oxygen concentrations in 2D and 3D cultures, as well as cell reactions to these concentrations. In this work, we modified two types of human endothelial cells-human microvascular (huMECs) and umbilical vein endothelial cells (huVECs) with genetically encoded hypoxia biosensors and monitored cell reactions in 2D to different oxygen concentrations. Moreover, we fabricated 3D cell spheroids of different cell numbers and sizes to reveal the onset of hypoxia in huVECs and huMECs. We could demonstrate a quantitative sensor response of two cell types to reduced oxygen supply in 2D and reveal different thresholds for hypoxic response. In 3D cell spheroids we could estimate critical construct sizes for the appearance of a hypoxic core. This work for the first time directly demonstrates different hypoxic signatures for huVECs and huMECs in 2D and 3D cell culture systems.

Supporting Weight Management during COVID-19 (SWiM-C): twelve-month follow-up of a randomised controlled trial of a web-based, ACT-based, guided self-help intervention.

OBJECTIVES: We developed a guided self-help intervention (Supporting Weight Management during COVID-19, "SWiM-C") to support adults with overweight or obesity in their weight management during the COVID-19 pandemic. This parallel, two-group trial (ISRCTN12107048) evaluated the effect of SWiM-C on weight and determinants of weight management over twelve months. METHODS: Participants (≥18 years, body-mass-index ≥25 kg/m2) were randomised to the SWiM-C intervention or to a standard advice group (unblinded). Participants completed online questionnaires at baseline, four months, and twelve months. The primary outcome was change in self-reported weight from baseline to twelve months; secondary outcomes were eating behaviour (uncontrolled eating, emotional eating, cognitive restraint of food intake), experiential avoidance, depression, anxiety, stress, wellbeing and physical activity. INTERVENTIONS: SWiM-C is based on acceptance and commitment therapy (ACT). Participants had access to an online web platform with 12 weekly modules and email and telephone contact with a trained, non-specialist coach. Standard advice was a leaflet on managing weight and mood during the COVID-19 pandemic. RESULTS: 388 participants were randomised (SWiM-C: n = 192, standard advice: n = 196). The baseline-adjusted difference in weight change between SWiM-C (n = 119) and standard advice (n = 147) was -0.81 kg (95% CI: -2.24 to 0.61 kg). SWiM-C participants reported a reduction in experiential avoidance (-2.45 [scale:10-70], 95% CI: -4.75 to -0.15), uncontrolled eating (-3.36 [scale: 0-100], 95% CI: -5.66 to -1.06), and emotional eating (-4.14 [scale:0-100], 95% CI: -7.25 to -1.02) and an increase in physical activity (8.96 [MET-min/week], 95% CI: 0.29 to 17.62) compared to standard advice participants. We found no evidence of an effect on remaining outcomes. No adverse events/side effects were reported. CONCLUSIONS: Whilst we were unable to conclude that the intervention had an effect on weight, SWiM-C improved eating behaviours, experiential avoidance and physical activity. Further refinement of the intervention is necessary to ensure meaningful effects on weight prior to implementation in practice. TRIAL REGISTRATION NUMBER: ISRCTN 12107048.

The impact of participant mental health on attendance and engagement in a trial of behavioural weight management programmes: secondary analysis of the WRAP randomised controlled trial.

BACKGROUND: Low attendance and engagement in behavioural weight management trials are common. Mental health may play an important role, however previous research exploring this association is limited with inconsistent findings. We aimed to investigate whether mental health was associated with attendance and engagement in a trial of behavioural weight management programmes. METHODS: This is a secondary data analysis of the Weight loss referrals for adults in primary care (WRAP) trial, which randomised 1267 adults with overweight or obesity to brief intervention, WW (formerly Weight Watchers) for 12-weeks, or WW for 52-weeks. We used regression analyses to assess the association of baseline mental health (depression and anxiety (by Hospital Anxiety and Depression Scale), quality of life (by EQ5D), satisfaction with life (by Satisfaction with Life Questionnaire)) with programme attendance and engagement in WW groups, and trial attendance in all randomised groups. RESULTS: Every one unit of baseline depression score was associated with a 1% relative reduction in rate of WW session attendance in the first 12 weeks (Incidence rate ratio [IRR] 0.99; 95% CI 0.98, 0.999). Higher baseline anxiety was associated with 4% lower odds to report high engagement with WW digital tools (Odds ratio [OR] 0.96; 95% CI 0.94, 0.99). Every one unit of global quality of life was associated with 69% lower odds of reporting high engagement with the WW mobile app (OR 0.31; 95% CI 0.15, 0.64). Greater symptoms of depression and anxiety and lower satisfaction with life at baseline were consistently associated with lower odds of attending study visits at 3-, 12-, 24-, and 60-months. CONCLUSIONS: Participants were less likely to attend programme sessions, engage with resources, and attend study assessments when reporting poorer baseline mental health. Differences in attendance and engagement were small, however changes may still have a meaningful effect on programme effectiveness and trial completion. Future research should investigate strategies to maximise attendance and engagement in those reporting poorer mental health. TRIAL REGISTRATION: The original trial ( ISRCTN82857232 ) and five year follow up ( ISRCTN64986150 ) were prospectively registered with Current Controlled Trials on 15/10/2012 and 01/02/2018.

European-wide policymaking at the urban level: a qualitative study.

BACKGROUND: Inter-urban area (UA) health inequalities can be as dramatic as those between high and low-income countries. Policies need to focus on the determinants of health specific to UAs to effect change. This study therefore aimed to determine the degree to which policymakers from different countries could make autonomous health and wellbeing policy decisions for their urban jurisdiction area. METHODS: We conducted a cross-sectional, qualitative interview study with policymakers recruited from eight European countries (N = 37). RESULTS: The reported autonomy among policymakers varied considerably between countries, from little or no autonomy and strict adherence to national directives (e.g. Slovak Republic) to a high degree of autonomy and ability to interpret national guidelines to local context (e.g. Norway). The main perceived barriers to implementation of local policies were political, and the importance of regular and effective communication with stakeholders, especially politicians, was emphasized. Having qualified health professionals in positions of influence within the UA was cited as a strong driver of the public health (PH) agenda at the UA level. CONCLUSION: Local-level policy development and implementation depends strongly on the degree of autonomy and independence of policymakers, which in turn depends on the organization, structure and financial budget allocation of PH services. While high levels of centralization in small, relatively homogenous countries may enhance efficient use of resources, larger, more diverse countries may benefit from devolution to smaller geographical regions.

The Role of Web-Based Health Information in Help-Seeking Behavior Prior to a Diagnosis of Lung Cancer: A Mixed-Methods Study.

BACKGROUND: Delays to diagnosis in lung cancer can lead to reduced chance of survival, and patients often wait for several months before presenting symptoms. The time between first symptom recognition until diagnosis has been theorized into three intervals: symptom appraisal, help-seeking, and diagnostic interval (here: "pathway to diagnosis"). Interventions are needed to reduce delays to diagnosis in lung cancer. The Web has become an important lay health information source and could potentially play a role in this pathway to diagnosis. OBJECTIVE: Our overall aim was to gain a preliminary insight into whether Web-based information plays a role in the pathway to diagnosis in lung cancer in order to assess whether it may be possible to leverage this information source to reduce delays to diagnosis. METHODS: Patients diagnosed with lung cancer in the 6 months before study entry completed a survey about whether (and how, if yes) they had used the Web to appraise their condition prior to diagnosis. Based on survey responses, we purposively sampled patients and their next-of-kin for semistructured interviews (24 interviews; 33 participants). Interview data were analyzed qualitatively using Framework Analysis in the context of the pathway to diagnosis model. RESULTS: A total of 113 patients completed the survey (age: mean 67.0, SD 8.8 years). In all, 20.4% (23/113) reported they or next-of-kin had researched their condition online before the diagnosis. The majority of searches (20/23, 87.0%) were conducted by or with the help of next-of-kin. Interview results suggest that patients and next-of-kin perceived an impact of the information found online on all three intervals in the time to diagnosis. In the appraisal interval, participants used online information to evaluate symptoms and possible causes. In the help-seeking interval, the Web was used to inform the decision of whether to present to health services. In the diagnostic interval, it was used to evaluate health care professionals' advice, to support requests for further investigation of symptoms, and to understand medical jargon. Within this interval, we identified two distinct subintervals (before/after relevant diagnostic tests were initiated), in which the Web reportedly played different roles. CONCLUSIONS: Because only 20.4% of the sample reported prediagnosis Web searches, it seems the role of the Web before diagnosis of lung cancer is at present still limited, but this proportion is likely to increase in the future, when barriers such as unfamiliarity with technology and unwillingness to be informed about one's own health are likely to decrease. Participants' perceptions suggest that the Web can have an impact on all three intervals in the pathway to diagnosis. Thus, the Web may hold the potential to reduce delays in the diagnostic process, and this should be explored in future research and interventions. Our results also suggest a division of the diagnostic interval into two subintervals may be useful.

Web Use for Symptom Appraisal of Physical Health Conditions: A Systematic Review.

BACKGROUND: The Web has become an important information source for appraising symptoms. We need to understand the role it currently plays in help seeking and symptom evaluation to leverage its potential to support health care delivery. OBJECTIVE: The aim was to systematically review the literature currently available on Web use for symptom appraisal. METHODS: We searched PubMed, EMBASE, PsycINFO, ACM Digital Library, SCOPUS, and Web of Science for any empirical studies that addressed the use of the Web by lay people to evaluate symptoms for physical conditions. Articles were excluded if they did not meet minimum quality criteria. Study findings were synthesized using a thematic approach. RESULTS: A total of 32 studies were included. Study designs included cross-sectional surveys, qualitative studies, experimental studies, and studies involving website/search engine usage data. Approximately 35% of adults engage in Web use for symptom appraisal, but this proportion varies between 23% and 75% depending on sociodemographic and disease-related factors. Most searches were symptom-based rather than condition-based. Users viewed only the top search results and interacted more with results that mentioned serious conditions. Web use for symptom appraisal appears to impact on the decision to present to health services, communication with health professionals, and anxiety. CONCLUSIONS: Web use for symptom appraisal has the potential to influence the timing of help seeking for symptoms and the communication between patients and health care professionals during consultations. However, studies lack suitable comparison groups as well as follow-up of participants over time to determine whether Web use results in health care utilization and diagnosis. Future research should involve longitudinal follow-up so that we can weigh the benefits of Web use for symptom appraisal (eg, reductions in delays to diagnosis) against the disadvantages (eg, unnecessary anxiety and health care use) and relate these to health care costs.

Understanding Spiritual Care: The Faith-Hope-Love Model of Spiritual Wellness.

Spiritual care has been associated with positive patient outcomes. Although nurses want to provide spiritual care, many have difficulty conceptualizing spiritual care outside of religion and religious activities. The Faith-Hope-Love Model of Spiritual Wellness, a theoretical model of spirituality and spiritual well-being, grounded in Christian theology and biblical text, can help nurses provide spiritual support to patients and families from multiple faith traditions or those without a faith background. Spirituality concepts are discussed, and description of how spirituality is related to finding meaning and purpose in life along with a summary of the spiritual needs identified from healthcare literature and the Bible, are provided.

Biglycan deficiency: increased aortic aneurysm formation and lack of atheroprotection.

Proteoglycans of the arterial wall play a critical role in vascular integrity and the development of atherosclerosis owing to their ability to organize extracellular matrix molecules and to bind and retain atherogenic apolipoprotein (apo)-B containing lipoproteins. Prior studies have suggested a role for biglycan in aneurysms and in atherosclerosis. Angiotensin II (angII) infusions into mice have been shown to induce abdominal aortic aneurysm development, increase vascular biglycan content, increase arterial retention of lipoproteins, and accelerate atherosclerosis. The goal of this study was to determine the role of biglycan in angII-induced vascular diseases. Biglycan-deficient or biglycan wildtype mice crossed to LDL receptor deficient (Ldlr-/-) mice (C57BL/6 background) were infused with angII (500 or 1000ng/kg/min) or saline for 28days while fed on normal chow, then pumps were removed, and mice were switched to an atherogenic Western diet for 6weeks. During angII infusions, biglycan-deficient mice developed abdominal aortic aneurysms, unusual descending thoracic aneurysms, and a striking mortality caused by aortic rupture (76% for males and 48% for females at angII 1000ng/kg/min). Histological analyses of non-aneurysmal aortic segments from biglycan-deficient mice revealed a deficiency of dense collagen fibers and the aneurysms demonstrated conspicuous elastin breaks. AngII infusion increased subsequent atherosclerotic lesion development in both biglycan-deficient and biglycan wildtype mice. However, the biglycan genotype did not affect the atherosclerotic lesion area induced by the Western diet after treatment with angII. Biglycan-deficient mice exhibited significantly increased vascular perlecan content compared to biglycan wildtype mice. Analyses of the atherosclerotic lesions demonstrated that vascular perlecan co-localized with apoB, suggesting that increased perlecan compensated for biglycan deficiency in terms of lipoprotein retention. Biglycan deficiency increases aortic aneurysm development and is not protective against the development of atherosclerosis. Biglycan deficiency leads to loosely packed aortic collagen fibers, increased susceptibility of aortic elastin fibers to angII-induced stress, and up-regulation of vascular perlecan content.

Backcasting the decline of a vulnerable Great Plains reproductive ecotype: identifying threats and conservation priorities.

Conservation efforts for threatened or endangered species are challenging because the multi-scale factors that relate to their decline or inhibit their recovery are often unknown. To further exacerbate matters, the perceptions associated with the mechanisms of species decline are often viewed myopically rather than across the entire species range. We used over 80 years of fish presence data collected from the Great Plains and associated ecoregions of the United States, to investigate the relative influence of changing environmental factors on the historic and current truncated distributions of the Arkansas River shiner Notropis girardi. Arkansas River shiner represent a threatened reproductive ecotype considered especially well adapted to the harsh environmental extremes of the Great Plains. Historic (n = 163 records) and current (n = 47 records) species distribution models were constructed using a vector-based approach in MaxEnt by splitting the available data at a time when Arkansas River shiner dramatically declined. Discharge and stream order were significant predictors in both models; however, the shape of the relationship between the predictors and species presence varied between time periods. Drift distance (river fragment length available for ichthyoplankton downstream drift before meeting a barrier) was a more important predictor in the current model and indicated river segments 375-780 km had the highest probability of species presence. Performance for the historic and current models was high (area under the curve; AUC > 0.95); however, forecasting and backcasting to alternative time periods suggested less predictive power. Our results identify fragments that could be considered refuges for endemic plains fish species and we highlight significant environmental factors (e.g., discharge) that could be manipulated to aid recovery.

Warfarin dosing and body mass index.

BACKGROUND: Warfarin is still the most commonly used anticoagulant for the treatment of venous thromboembolism and other hypercoagulable states. Warfarin metabolism is affected by multiple factors, including diet, medications, and individual patient characteristics. As both underdosing and overdosing can increase risks to patients, several studies have attempted to develop dosing protocols. However, few have investigated how patient weight and body mass index (BMI) affect warfarin dosing. OBJECTIVE: The objective of this study was to determine the association between BMI and the total weekly dose (TWD) of warfarin. METHODS: In this retrospective study, we identified patients taking warfarin who had an international normalized ratio (INR) within the therapeutic range to assess if there was a significant correlation between TWD, that is, maintenance warfarin dosing, and BMI in obese and nonobese patients. RESULTS: A total of 831 patients were studied, with a BMI range between 13.4 and 63.1 kg/m(2). We found that BMI is positively correlated with the total weekly warfarin dose. Our study showed that for each 1-point increase in BMI, the weekly warfarin dose increased by 0.69 mg. We found that the average warfarin weekly dose in this population can be estimated using the formula: 12.34 + 0.69 × BMI. CONCLUSION: There is an association between BMI and the TWD of warfarin. This could have dosing implications for both patients and prescribers, as patients with a high BMI will be expected to require higher doses of warfarin to maintain a therapeutic INR.

The association between patterns of weight change, diabetes status and glycaemia among adults with overweight and obesity.

AIMS: To investigate the associations between weight change patterns and 5-year incident non-diabetic hyperglycaemia (NDH), and glycated haemoglobin (HbA1c) levels among individuals who had overweight or obesity. METHODS: This longitudinal cohort study (N = 435) pooled data from a weight management trial. Participants were adults with a body mass index of ≥28 kg/m2. They were categorised as "no weight loss", "maintainers", and "regainers" based on their weight at 3 months and 12 months after baseline. Multivariable logistic regression models and linear regressions were conducted to examine the associations. RESULTS: Between 1-year and 5-year follow-ups, 77 participants developed NDH. We found no statistically significant association between weight change patterns and incident NDH at 5 years. Among weight loss maintainers, mean HbA1c was -0.15% (95% confidence intervals (CI): -0.22, -0.10) lower after 1 year and -0.15% (95% CI: -0.23, -0.06) lower after 5 years compared to the no weight loss group. There was no difference between weight loss regainers and no weight loss group in HbA1c levels. CONCLUSIONS: Compared to those who did not lose weight, participants who maintained their weight loss had lower HbA1c levels after 1 year and 5 years, which highlights the importance of providing long-term support to prevent weight regain.

Postoperative Adjacent Segment Disease in Minimally Invasive Transforaminal Lumbar Interbody Fusion with Adjacent Laminectomy for Grade I-II Spondylolisthesis and Adjacent Spinal Stenosis.

BACKGROUND AND OBJECTIVES: Studies have demonstrated increased risk of adjacent segment disease (ASD) after open fusion with adjacent-level laminectomy, with rates ranging from 16%-47%, potentially related to disruption of the posterior ligamentous complex. Minimally invasive surgical (MIS) approaches may offer a more durable result. We report institutional outcomes of simultaneous MIS transforaminal lumbar interbody fusion (MISTLIF) and adjacent-level laminectomy for patients with low grade spondylolisthesis and ASD. METHODS: Retrospective analysis was performed on patients who underwent MISTLIF with adjacent level laminectomy to treat grade I-II spondylolisthesis with adjacent stenosis at a single institution from 2007-2022. RESULTS: A total of 34 patients met criteria, with mean follow-up of 23.1 months. In total, 37 levels were fused and 45 laminectomies performed. In this group, 21 patients received a single level laminectomy and single-level MISTLIF, 10 patients received a 2-level laminectomy and single-level MISTLIF, 2 patients received a single-level laminectomy and 2-level MISTLIF, and 1 patient received a 2-level laminectomy and 2-level MISTLIF. Three (8.8%) patients experienced clinically significant postoperative ASD requiring reoperation. Three other patients required reoperation for other reasons. Multiple logistic regression did not reveal any association between development of ASD and surgical covariates. CONCLUSION: MISTLIF with adjacent-level laminectomy demonstrated a favorable safety profile with rates of postoperative ASD lower than published rates after open fusion and on par with the published rates of ASD from MISTLIF alone. Future prospective studies may better elucidate the durability of adjacent-level laminectomies when performed alongside MISTLIF, but retrospective data suggests it is safe and durable.

The relationship of within-individual and between-individual variation in mental health with bodyweight: An exploratory longitudinal study.

BACKGROUND: Poor mental health is associated with obesity, but existing studies are either cross-sectional or have long time periods between measurements of mental health and weight. It is, therefore, unclear how small fluctuations in mental wellbeing within individuals predict bodyweight over short time periods, e.g. within the next month. Studying this could identify modifiable determinants of weight changes and highlight opportunities for early intervention. METHODS: 2,133 UK adults from a population-based cohort completed monthly mental health and weight measurements using a mobile app over a period of 6-9 months. We used random intercept regression models to examine longitudinal associations of depressive symptoms, anxiety symptoms and stress with subsequent weight. In sub-group analyses, we included interaction terms of mental health variables with baseline characteristics. Mental health variables were split into "between-individual" measurements (= the participant's median score across all timepoints) and "within-individual" measurements (at each timepoint, the difference between the participant's current score and their median). RESULTS: Within-individual variation in depressive symptoms predicted subsequent weight (0.045kg per unit of depressive symptom severity, 95% CI 0.021-0.069). We found evidence of a moderation effect of baseline BMI on the association between within-individual fluctuation in depressive symptoms and subsequent weight: The association was only apparent in those with overweight/obesity, and it was stronger in those with obesity than those with overweight (BMI<25kg/m2: 0.011kg per unit of depressive symptom severity [95% CI -0.017 to 0.039]; BMI 25-29.9kg/m2: 0.052kg per unit of depressive symptom severity [95%CI 0.010-0.094kg]; BMI≥30kg/m2: 0.071kg per unit of depressive symptom severity [95%CI 0.013-0.129kg]). We found no evidence for other interactions, associations of stress and anxiety with weight, or for a reverse direction of association. CONCLUSION: In this exploratory study, individuals with overweight or obesity were more vulnerable to weight gain following higher-than-usual (for that individual) depressive symptoms than individuals with a BMI<25kg/m2.

The moderating and mediating role of eating behaviour traits in acceptance and commitment therapy-based weight management interventions: protocol for an individual participant data meta-analysis.

INTRODUCTION: Precision medicine approaches to obesity aim to maximise treatment effectiveness by matching weight management interventions (WMIs) to characteristics of individuals, such as eating behaviour traits (EBTs). Acceptance and commitment therapy (ACT)-based WMIs may address EBTs such as emotional and uncontrolled eating more effectively than standard interventions, and might be most effective in people with high levels of these traits. However, few studies have examined this directly. We will examine (a) whether ACT-based interventions are more effective for people with certain levels of EBTs (ie, moderation) and (b) whether ACT-based interventions operate through changes in EBTs (ie, mediation). METHODS AND ANALYSIS: This individual participant data (IPD) meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data guidance. We will include studies on ACT-based WMIs that assessed EBTs in people with a body mass index ≥25 kg/m2. We identified studies by screening studies included in a previous review of third wave cognitive behavioural interventions, and updating the search to 20 June 2022. We will request IPD from eligible published and unpublished studies. We will harmonise and re-analyse data using a two-stage random effects meta-analysis pooling within-trial interactions to investigate moderating effects and using a one-stage simultaneous equation model to examine mediating effects. We will assess the risk of bias in included studies using the Cochrane Risk of Bias tool 2 and the Risk of Bias in Non-randomised Studies of Interventions tool. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Cambridge Psychology Research Ethics Committee (Application No: PRE.2023.121). Data sharing will follow data transfer agreements and coauthorship will be offered to investigators contributing data. Findings will be disseminated through peer-reviewed journals and conferences and will contribute to the lead author's PhD thesis. PROSPERO REGISTRATION NUMBER: CRD42022359691.

Association between Indicators of Inequality and Weight Change following a Behavioural Weight Loss Intervention.

INTRODUCTION: Weight loss through behavioural weight management interventions can have important health benefits for people with obesity. However, to maximise the health benefits, weight loss must be maintained. Evidence suggests that behavioural weight loss interventions do not exacerbate inequalities in the short term. However, no study has yet considered whether inequalities exist in long-term weight change following intervention. We aimed to investigate if there are inequalities in weight change following weight loss intervention. METHODS: We conducted a cohort analysis of data from the Weight Loss Referrals for Adults in Primary Care (WRAP) trial (N = 1,267). WRAP randomised participants to receive a brief intervention information booklet or vouchers for 12-weeks or 52-weeks of WW (formerly WeightWatchers) and followed them for 5 years. Multiple linear regression estimated the association between exposures (indicators of inequality) and outcomes (change in weight between 1- and 5-years). Each model was adjusted for the intervention group, baseline weight, weight change between baseline and 1-year, research centre, and source of the 5-year weight data. RESULTS: Of the 1,267 participants in WRAP, 708 had weight change data available. Mean weight change between 1- and 5-years was +3.30 kg (SD 9.10 kg). A 1 year difference in age at baseline was associated with weight change of 0.11 kg ((95% CI 0.06, 0.16), p < 0.001). We did not find evidence of associations between ethnicity, gender, education, indices of multiple deprivation, household income, or other family members participating in a weight loss programme and weight change. CONCLUSION: Except for age, we did not find evidence of inequalities in weight change following a behavioural intervention. Findings further support the use of behavioural weight management interventions as part of a systems-wide approach to improving population health.

Are there inequalities in the attendance and effectiveness of behavioural weight management interventions for adults in the UK? Protocol for an individual participant data (IPD) meta-analysis.

INTRODUCTION: It is important to identify whether behavioural weight management interventions work well across different groups in the population so health inequalities in obesity are not widened. Previous systematic reviews of inequalities in the attendance and effectiveness of behavioural weight management interventions have been limited because few trials report relevant analyses and heterogeneity in the categorisation of inequality characteristics prevents meta-analysis. An individual participant data meta-analysis (IPD-MA) allows us to reanalyse all trials with available data in a uniform way. We aim to conduct an IPD meta-analysis of UK randomised controlled trials to examine whether there are inequalities in the attendance and effectiveness of behavioural weight interventions. METHODS AND ANALYSIS: In a recently published systematic review, we identified 17 UK-based randomised controlled trials of primary care-relevant behavioural interventions, conducted in adults living with overweight or obesity and reporting weight outcomes at baseline and 1-year follow-up. The corresponding author of each trial will be invited to contribute data to the IPD-MA. The outcomes of interest are weight at 12-months and intervention attendance (number of sessions offered vs number of sessions attended). We will primarily consider whether there is an interaction between intervention group and characteristics where inequalities occur, such as by gender/sex, socioeconomic status or age. The IPD-MA will be conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses of IPD guidelines. ETHICS AND DISSEMINATION: No further ethical approval was required as ethical approval for each individual study was obtained by the original trial investigators from appropriate ethics committees. The completed IPD-MA will be disseminated at conferences, in a peer-reviewed journal and contribute to the lead author's PhD thesis. Investigators of each individual study included in the final IPD-MA will be invited to collaborate on any publications that arise from the project.