Journal of Psychosomatic Research

PurposeSurvivors of severe COVID-19 commonly experience post-intensive care syndrome (PICS), which includes depression and fatigue. Fatigue is far more common and may inflate depression severity given overlapping symptoms. We sought to disentangle fatigue from depression in PICS. MethodsWe conducted a cross-sectional analysis of the RAFT COVID study, a national multicenter longitudinal cohort of severe prolonged COVID-19 survivors. We included participants who completed validated surveys at 1-year from hospitalization for depression (PHQ-9) and fatigue (FACIT-Fatigue). We described correlation of FACIT-fatigue with the PHQ9, and separately with PHQ-2 and PHQ-7, which both omit the two items we hypothesized are influenced by fatigue--tiredness and sleeping. Using a MIMIC model, we performed differential item functioning to evaluate the impact of fatigue on depression directly through these two questions and indirectly with the latent depression construct. We then compared PHQ-7 to PHQ-9 scores by fatigue status. ResultsAmong 82 participants, 61.0% reported fatigue (reverse-scored FACIT-Fatigue [&ge;]9), and 15.9% moderately severe depression (PHQ-9 [&ge;]10). FACIT-fatigue was strongly correlated with PHQ-9 (r=.87, p<.001), but less so for PHQ-2 (r=.76, p<.001) and PHQ-7 (r=.82, p<.001). The MIMIC model identified significant direct effects on tiredness ({lambda}=.89, p<.001) and sleep ({lambda}=.52, p<.001). Among fatigued participants, the rescaled PHQ-7 was lower than the PHQ-9 (median of 4.5, IQR 1.50-9.75, vs 7, IQR 4-9.75). ConclusionsFatigue significantly inflated depression symptoms in severe COVID-19 survivors through tiredness and sleeping PHQ-9 items. PHQ-2 may better screen for true depressive symptoms in PICS, minimizing the risk of misdiagnosis and overtreatment. PLAIN ENGLISH SUMMARYSurvivors of severe COVID-19 illness commonly experience post-intensive care syndrome (PICS), which includes depression and fatigue. Fatigue is far more common and may inflate depression severity given overlapping symptoms. We sought to disentangle fatigue from depression in PICS. We found that the presence of fatigue inflated depression severity through symptoms of tiredness and difficulty sleeping, which are two of the nine items of a commonly used depression screening tool, known as the Patient Health Questionnaire-9 (PHQ-9). Depression screening tools that omit these two items, such as the PHQ-2, may better screen for depressive symptoms in PICS, minimizing the risk of overestimating depression symptoms and potentially misdiagnosis.

BackgroundFunctional motor disorder (FMD) is a common and disabling condition with incompletely understood pathophysiology. Eye-tracking offers a method to objectively examine cognitive and motor control processes and their underlying neural pathways. We aimed to quantify saccade, blink and pupil responses in FMD and healthy controls performing an interleaved pro-/anti-saccade task, and to investigate the relationships between oculomotor measures and motor and non-motor symptom severity. MethodsWe conducted video-based eye-tracking in 104 patients with clinically definite FMD and 115 age- and sex-matched healthy controls performing the saccade task. Patients completed questionnaires on depressive, pain-related, dissociative, non-motor somatic symptoms. Clinician-rated motor severity and centrally acting medication was recorded in FMD patients. ResultsCompared to controls, FMD patients showed increased anti-saccade error rates (p < 0.001), anticipatory saccades (p [&le;] 0.003), altered blink distribution (p < 0.001), and reduced pupil dilation velocity (p < 0.001). However, reduced pupil dilation velocity was not significant in subsample of unmedicated patients. Higher anti-saccade error rates were significantly associated with depressive symptoms, pain severity, dissociative symptoms, non-motor somatic symptom burden, and motor severity (all p < 0.05). ConclusionsWe hypothesize that the altered saccade and blink responses result from altered processing in the frontal cortex and basal ganglia which provide critical input to brainstem oculomotor control areas in FMD. These results support neurobiological models proposing altered predictive and attentional processing underlying FMD. Association between oculomotor measures and symptom severity suggests that specific cognitive abnormalities may play a role in the pathophysiology of these symptoms in FMD. WHAT IS ALREADY KNOWN ON THIS TOPICFMD is increasingly interpreted through predictive coding models suggesting abnormalities in predictions about motor and sensory states driven by abnormally focused attention. Yet the underlying neurobiology remains poorly defined. Empirical studies directly probing basic predictive processes in FMD are scarce, and implicit cognitive-motor interactions, particularly those involving motor learning and adaptation, have been insufficiently explored. WHAT THIS STUDY ADDSOnly two previous studies have used eye-tracking in FMD, focusing mainly on diagnostic saccadic markers. Using time-series analyses of saccadic, blink, and pupillary data, we show abnormalities in inhibitory control, predictive processing, and implicit learning. Due to strong homology between human and primate neurophysiology and neuroimaging findings in oculomotor control, the findings can be linked to dysfunction within cortico-basal ganglia circuits. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYOculomotor abnormalities correlated with motor and non-motor symptom severity, indicating mechanistic relevance. The findings provide empirical support for predictive coding accounts and point to involvement of subcortical structures including projections from the frontal cortex to the basal ganglia. This highlights the value of studying cortico-basal ganglia circuits with implications for treatment and of developing oculomotor measures as potential biomarkers in FMD.

Background Unplanned hospital admissions in Inflammatory Bowel Diseases (IBD) account for nearly three-quarters of IBD inpatient stays in the United Kingdom. Although costly to services and distressing for patients, research exploring experiences and potential drivers of admissions is limited. We undertook a qualitative study to explore the healthcare experiences and access needs of people with IBD who had unplanned admissions, along with their caregivers and clinicians. Methods Semi-structured interviews with 25 participants from a single tertiary IBD service in England (17 people with IBD, 3 informal caregivers, 5 clinicians) were conducted. We applied thematic framework analysis, guided by the Candidacy Framework, and worked with 2 patient and public contributors to generate final themes. Results We identified four themes: 1) Difficulties in Identifying flares and asserting severity before admission, summarised the prevailing uncertainty in identifying a flare and access to timely IBD care. 2) Navigating a disjointed healthcare system, highlighted how lack of care plans and systemic barriers can delay access. 2) Emergency care access challenges highlighted the gaps in emergency and inpatient care during flares. Whilst 4) fighting for care and individual advocacy needs, described the persistent assertion for care that may disproportionally impact access to vulnerable groups, also highlighting the importance of positive interpersonal relationships. Conclusions Individual, interpersonal and healthcare factors across the patient pathway were perceived to shape access to care in unplanned IBD admissions. Potentially reducing admissions requires proactive strategies, including the integration of patient education, monitoring tools, establishment of specialist rapid-access pathways, and formal psychological support to address barriers to access.

Despite the global prevalence of postpartum depression (PPD), current referral uptake rates are far from satisfactory. While some qualitative studies have investigated factors affecting PPD referrals, a gap in quantitative analysis remains. Addressing this, our study utilized a discrete choice experiment (DCE) to understand the procedural elements influencing PPD referral uptake among diagnosed women. The DCE was conducted via home visits by healthcare providers and a comprehensive mobile app questionnaire. We constructed seven distinct referral attributes to explore participants' preferences, analyzed using mixed logit models and latent class analysis. This analysis identified key determinants and revealed the heterogeneities in referral preferences. A total of 698 individuals completed the DCE questionnaire. All assessed attributes, except for Accompaniment (going to clinic with a family member), were important determinants of preference. Participants generally preferred referrals to psychiatric clinics, face-to-face consultations, lower costs, and shorter waiting times. Significantly, participants' personal and socio-demographic characteristics also played a critical role in their referral preferences. Latent class analysis categorized participants into four distinct groups based on their preferences, with treatment cost and waiting times being the most decisive factors. In conclusion, the preference for PPD referrals is predominantly driven by convenience and access to specialist care. To enhance referral uptake, developing flexible and personalized referral programs that cater to these preferences is crucial.

Introduction: Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) is a debilitating condition characterised by severe fatigue and post-exertional malaise (PEM). Reported neuropsychophysiological abnormalities suggest ME/CFS is multifactorial, but current knowledge remains fragmented. This study protocol outlines a multimodal investigation designed to (1) compare neuropsychophysiological mechanisms between ME/CFS patients and healthy participants, (2) test an integrative model of ME/CFS, (3) identify neuropsychophysiological subgroups within the patient population, and (4) identify predictors of symptom response during rehabilitation. Methods and analysis: This study will enroll 115 ME/CFS patients and 55 healthy participants. Groups will be comparable in age, sex, and education level, with a larger patient sample enabling subgroup and longitudinal analyses. A cross-sectional assessment at baseline will be carried out in both groups. Patients will then be evaluated longitudinally throughout a standardized cognitive-behavioral therapy rehabilitation program delivered as routine care. Baseline measures include systemic inflammation and general health biomarkers, measures of autonomic and central nervous system function, neuroinflammation (magnetic resonance spectroscopy, [18F]DPA714 PET in a subsample), serum short-chain fatty acid levels, gut microbiota composition and function, and neuroendocrine and self-reported responses to psychosocial stress. Fatigue severity (physical and cognitive) and PEM will be assessed through validated questionnaires, ecological momentary assessment, and laboratory tasks. These will be re-evaluated during therapy, and all non-neuroimaging measures will be repeated after the rehabilitation program. Statistical analyses will comprise multivariate analysis of variance, general linear models, classification algorithms, structural equation models, least absolute shrinkage selection operator principal component regression (LASSO-PCR), cluster analysis and latent class growth analysis (LCGA).

Oxytocin is a hypothalamic hormone and neuromodulator that has been linked to a variety of different functions, including parturition, social behavior, and cognitive processing. More recently, oxytocin has also been associated with metabolism and energy balance. However, evidence to date in this field has been inconsistent, especially in human research. To address this, we performed a preregistered systematic review and meta-analysis, which synthesized existing literature on the effect of exogenous oxytocin administration compared to a placebo on caloric intake and appetite in humans, using a living meta-analysis approach. Results indicated a significant, reductive effect of oxytocin administration on appetite in participants belonging to certain patient groups (e.g., obesity or type II diabetes; Hedges' g = -0.21). A separate moderator analysis evaluating oxytocin's effect on caloric intake revealed a conditional effect depending on the patient group, with the obesity group showing a significant effect. We did not find any statistically significant effects in healthy participants. However, further analyses revealed that these effects were also not equivalent, indicating that the data are currently too insensitive to draw clear conclusions. Taken together, the results provide some evidence for the role of oxytocin in regulating appetite in an anorexigenic, possibly homeostatic fashion. Future updates in this living meta-analysis may lead to more definitive conclusions.

Introduction/Aim: Type 2 diabetes (T2D) is a growing global health burden, with lifestyle behaviors playing a key role in its management. Physical activity (PA), sedentary behavior (SB), and sleep are increasingly conceptualized as interdependent components of 24-hour movement behaviors. While behavior change techniques (BCTs) are commonly used to target individual behaviors, their effectiveness across multiple behaviors in adults with T2D remains unclear. This systematic review and meta-analysis aimed to evaluate the effectiveness of behavior change interventions incorporating BCTs on PA, SB, and sleep outcomes, and to identify effective BCT clusters. Methods: A systematic search of PubMed, Web of Science, and Embase was conducted from inception to December 18, 2023. Randomized and non-randomized controlled trials including adults with T2D were eligible if they evaluated behavior change or lifestyle interventions targeting PA, SB, and/or sleep and included at least one BCT. Data extraction, BCT coding (using the BCT Taxonomy), and risk of bias assessment (Cochrane RoB 2) were performed independently by multiple reviewers. Meta-analyses using random-effects models were conducted for relevant outcomes. Subgroup analyses examined the effects of three common BCT clusters: goals and planning, feedback and monitoring, and social support. Results: Sixty-six studies (n = 18,725 participants) were included. Interventions significantly improved several PA outcomes, including steps/day (+1991 steps/day; p<0.001), total PA (SMD=0.36; p=0.02), moderate-to-vigorous PA (SMD=0.55; p<0.001), and light-intensity PA (SMD=0.62; p=0.01). Sedentary time decreased significantly (SMD=-0.32; p=0.008). Sleep quality improved (MD=-1.39; p=0.02), whereas sleep duration showed no significant change. Subgroup analyses demonstrated that BCT clusters involving goals and planning, feedback and monitoring, and social support were consistently associated with improvements in PA and SB, with comparable effect sizes to overall analyses. Effects on sleep outcomes were limited due to the small number of studies. Conclusion: Behavior change interventions incorporating BCTs effectively increase PA, reduce SB, and improve sleep quality in adults with T2D. BCTs such as goal setting, self-monitoring, feedback, and social support appear particularly beneficial. However, sleep - especially duration - remains underexplored. Future interventions should adopt a 24-hour movement behavior perspective and more explicitly integrate and report BCTs to optimize long-term diabetes management.

Background Chronic pain and depression are leading causes of disability and frequently co-occur. Depression presents with diverse symptoms, but despite this variability, the prevalence of individual depressive symptoms in chronic pain and the genetic and causal associations linking these traits remain poorly characterised. Methods Using data from 142,688 age- and sex-matched UK Biobank participants, we compared depressive symptom severity levels and item-level Patient Health Questionnaire-9 (PHQ-9) prevalences, spanning affective, cognitive and somatic domains, between participants with and without chronic pain. Using genome-wide association study (GWAS) summary statistics of multisite chronic pain (MCP), major depressive disorder (MDD), and individual symptoms of depression, genetic correlations and bidirectional causal effects between MCP and depressive phenotypes (MDD and individual symptoms) were estimated via linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomisation (MR), respectively. Results Depression (at every severity level) was more common in the chronic pain group compared to controls, with the largest between-group difference for severe symptoms (7.50-fold increase). All individual depressive symptoms were at least 2.79 times as prevalent in chronic pain. Additionally, chronic pain had a significant and positive genetic correlation with MDD (rg = 0.59) and all depressive symptoms (rg = [0.24, 0.55]). MR supported a bidirectional causal association between MCP and MDD (MCP[-&gt;]MDD: OR = 1.85, pFDR < 0.001, MDD[-&gt;]MCP: {beta} = 0.17, pFDR < 0.001). At the symptom level, MR indicated bidirectional effects between MCP and anhedonia (MCP[-&gt;]anhedonia: OR = 1.60, pFDR < 0.001, anhedonia[-&gt;]MCP: {beta} = 0.08, pFDR = 0.005), and unidirectional effects of MCP on appetite/weight gain (OR = 1.90, pFDR = 0.022) and appetite/weight loss (OR = 1.63, pFDR = 0.005), concentration problems (OR = 1.63, pFDR = 0.044), and suicidal thoughts (OR = 1.46, pFDR = 0.021). Additionally, genetic liability to concentration problems was associated with a lower risk of MCP ({beta} = -0.04, pFDR = 0.022). Conclusion Chronic pain is associated with a marked depressive burden spanning all symptom domains. Shared genetic architecture and symptom-specific causal pathways, particularly involving anhedonia, highlight potential targets for improved treatment of comorbid chronic pain and depression.

IntroductionThe bidirectional relationship between depression and type 2 diabetes (T2D) is well-established. Women are disproportionately affected by their co-occurrence, particularly during midlife, yet sex- and age-specific studies on phenotypic and mechanistic factors underlying risk for their co-occurrence are limited. The purpose of this study was to identify combined risk profiles (i.e., depression, T2D) in women during midlife and to determine if microRNAs (miRs) that are associated with high-risk profiles provide mechanistic insights into multimorbidity. Materials and MethodsThis study included baseline data from women during midlife (ages 40-64 years) who participated in the Diabetes Prevention Program (DPP) (n = 603). Unsupervised k-means clustering was used to identify multimorbid risk profiles. Clinical characteristics included for risk profiling included Beck Depression Inventory (BDI-I), age, BMI, waist circumference, triglycerides, high HDL, FBG, and HbA1c. Associations between risk profiles and individual miRs and principal components of co-expressed miRs were determined via logistic regression models adjusted for participant race and ethnicity. False discovery rate (q< 0.05) was used to control for multiple comparisons. ResultsTwo distinct profiles were identified, with the high-risk profile characterized by younger age yet higher adiposity, glycemic biomarkers, and depression symptom burden compared to the low-risk profile. MiR-320a and miR-320c were associated with increased odds of high-risk profile assignment, and a co-expression cluster enriched for miRs belonging to the miR-320 family (PC3) was significantly associated with increased odds of high-risk profile assignment. Across all models, Black race demonstrated at least threefold higher odds of high-risk profile assignment. DiscussionThese findings highlight distinct multimorbid risk profiles in women during midlife, emphasizing the potential utility of integrated, multidimensional approaches for risk stratification. Findings also revealed mechanisms that may underly risk for co-occurrence of T2D and depression in women during midlife and potential therapeutic targets for prevention and treatment.

BackgroundHealth-related quality of life is a key secondary endpoint in stroke trials. Differential item functioning (DIF) occurs when individuals with the same underlying HRQOL interpret and respond differently to questionnaire items due to group characteristics, potentially biasing treatment comparisons. This study evaluates DIF in the patient-reported five-level EuroQOL (EQ-5D-5L) among patients with acute ischemic stroke across age, sex, and treatment groups. MethodsData were obtained from the AcT trial, a registry-based randomized comparison of alteplase and tenecteplase. Patients completed the EQ-5D-5L at 90 days post-stroke. DIF was assessed using multigroup graded response models with the Wald-based sweep procedure, which accounts for between-group differences in latent trait distributions. We quantified effect sizes using signed weighted area between curves (sWABC), considering |sWABC| <0.10 as negligible. ResultsAmong 1,264 patients (51.2% tenecteplase; 46.5% female; 30.1% aged [&ge;]80). Omnibus testing revealed significant DIF only for age (X{superscript 2} = 86.9, p < 0.001); neither sex (X{superscript 2} = 31.7, p = 0.063) nor treatment (X{superscript 2} = 22.4, p = 0.379) showed evidence of DIF. At the item level, four items flagged for age-related DIF: self-care, usual activities, pain/discomfort, and anxiety/depression. However, only self-care (sWABC = -0.46) and usual activities (sWABC = - 0.34) showed moderate effects, while pain/discomfort (sWABC = -0.002) and anxiety/depression (sWABC = 0.09) were negligible. Importantly, factor scores from models with and without DIF adjustment correlated (correlation coefficient = 0.98). ConclusionsThe EQ-5D-5L appears to function equivalently across sex and treatment groups in this stroke population. Age-related DIF, though statistically detectable in physical functioning items, had little practical consequence for individual scores, findings that support the instruments use for HRQOL comparisons in stroke trials. RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

ObjectiveTo examine the bidirectional relationships between depression, anxiety, neuroticism, and urinary incontinence in women. DesignA prospective time-to-event and two-sample Mendelian randomisation (MR) study. SettingIndividual participant data from the UK Biobank and summary genome-wide association (GWAS) study data from international consortia. ParticipantsUp to 118 526 UK Biobank women with linked health records and up to 1.6 million participants with GWAS summary data. Main outcome measuresUrinary incontinence (UI) and its subtypes (stress, urge, mixed), urinary urgency (irrespective of leakage), depression, anxiety, and neuroticism. ResultsWe triangulated evidence to demonstrate bidirectional relationships between depression/anxiety and UI. In prospective analyses adjusted for confounders, depression was associated with a higher rate of new onset UI (any UI: Hazard Ratio (HR) 1.67; 95% Confidence Intervals (CI) 1.55 to 1.81) and its subtypes, with the strongest associations observed for mixed UI (HR 1.91; 95%CI 1.59 to 2.31). Similarly, anxiety and higher neuroticism scores were prospectively associated with UI and its subtypes. In the reverse direction, all UI subtypes were associated with a higher rate of new onset depression (e.g. any UI: HR 1.40; 95%CI 1.27 to 1.54) and anxiety (e.g. any UI: HR 1.28; 95%CI 1.17 to 1.39). Two-sample MR provided evidence for a causal effect of genetic liability to depression and neuroticism on UI and its subtypes (e.g. depression on any UI: ORivw; 1.25 95%CI 1.16 to 1.35). Evidence for a causal effect in the reverse direction was weaker, with modest effects of genetic liability to any UI on depression. Little evidence was found for causal effects of anxiety with UI subtypes in either direction. Results were largely robust to sensitivity analyses. ConclusionWe find evidence of bidirectional relationships between depression/anxiety and UI. Evidence that depression, anxiety and neuroticism are predictors of UI onset has implications for treatment. Research is needed to examine if treatments for depression/anxiety could be effective in alleviating UI. KEY MESSAGEO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIUrinary incontinence (UI) co-occurs with depression and anxiety, but the exact nature of the relationship is poorly understood because much of the existing evidence comes from cross-sectional studies. C_LIO_LIAmongst the existing prospective studies, only one used a clinically validated questionnaire to assess UI, few distinguished between UI subtypes (stress, urgency and mixed UI), and some did not adjust for important confounders. C_LIO_LIIt is commonly believed that depression and anxiety are consequences of UI; if they are also causes of UI this has important implications for clinical care. C_LI What the study addsO_LIOur study demonstrates that the relationship between UI and depression/anxiety is bidirectional; We found that depression, anxiety and neuroticism (a personality trait characterised by a disposition to experience depression and anxiety) are predictors of UI onset and that UI is associated with new onset depression and anxiety. C_LIO_LIDepression and anxiety are not routinely assessed in urology clinics, and a continued failure to recognise their contribution to the onset and persistence of UI could be a cause of low success rates of existing treatments for UI. C_LI

BackgroundNarcolepsy is a debilitating sleep disorder caused by hypocretin deficiency. Aside from its role to induce wakefulness, hypocretin is linked to modulated appetite and metabolism, often resulting in weight gain. Study objectivesWe aimed to unravel the comprehensive epidemiological connection between narcolepsy and major cardiometabolic outcomes. MethodsWe analyzed cardiovascular and metabolic disease distribution in the FinnGen study. Using longitudinal electronic health records, we assessed associations between narcolepsy, cardiac/metabolic markers, and prescriptions for relevant drugs. ResultsOur findings demonstrate significant associations between narcolepsy and metabolic traits (OR [95% CI] = 2.65 [1.81, 3.89]) as well as stroke (OR = 2.36 [1.38, 4.04]). Narcolepsy patients exhibit a less favourable metabolic profile, including higher glucose levels (OR = 1.1143 [1.0599, 1.1715]) and dyslipidaemia. This is supported by increased prescriptions of insulin (OR = 2.269 [1.46, 3.53]), simvastatin (OR = 2.292 [1.59, 3.31]), and metformin (OR = 2.327 [1.66, 3.25]), reflecting high metabolic disturbances. Furthermore, positive associations with antihypertensive and antiplatelet medications were observed, consistent with elevated cardiovascular risk. ConclusionTaken together, our findings highlight the cardiometabolic burden in narcolepsy. This study enhances understanding of the metabolic and cardiovascular consequences of narcolepsy and offers timely guidance for effective disease control. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/26351468v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@19f5783org.highwire.dtl.DTLVardef@2a648corg.highwire.dtl.DTLVardef@12f2b9eorg.highwire.dtl.DTLVardef@1d8baaf_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background: Psychological distress is common in chronic kidney disease (CKD) and is associated with reduced quality of life, treatment non-adherence, and worse clinical outcomes. Distress in CKD is also linked to difficulties adjusting to the demands of illness management. Despite this, psychological support remains inconsistently integrated within kidney care pathways, and existing interventions often lack clear theoretical specification and explicit targeting of mechanisms underpinning adjustment to CKD. Objectives: To describe the systematic development of iADJUST, a theory-informed patient co-designed digital psychological intervention targeting key cognitive and behavioural mechanisms involved in adjustment to CKD. Methods: Intervention development was guided by the Medical Research Council framework for complex interventions. A structured, iterative process integrated empirical evidence, psychological theory, and patient and public involvement and engagement. The Common-Sense Model of Self-Regulation and cognitive behavioural theories informed the identification of modifiable maintaining mechanisms associated with adjustment to CKD. Intervention components were mapped onto these mechanisms and refined through co-design with people living with CKD. Results: iADJUST is a six-session self-guided digital psychological intervention delivered over 12 weeks and supplemented by therapist contact. The intervention targets illness-related uncertainty, fatigue-related activity dysregulation, catastrophic what-if thinking, self-critical evaluation, and behavioural withdrawal. It integrates psychoeducation, cognitive and behavioural strategies, maintenance planning, and elements from acceptance and commitment therapy and compassion-focused approaches. Content is delivered through video, audio, and guided tasks and activities. Conclusion: iADJUST provides a theory-informed, evidence-based psychological intervention for CKD explicitly mapping intervention components to maintaining cognitive and behavioural mechanisms implicated in adjustment. Feasibility evaluation is underway.

Abstract Background Between 2021 and 2022, primary care obesity management was entering the early diffusion phase of newer anti obesity pharmacotherapy, as GLP1 based treatments began reshaping expectations. However, it was unclear whether primary care clinicians and practice environments were prepared to deliver comprehensive obesity care. (1,2) Methods In 2021 to 2022, we surveyed 276 clinicians from three cohorts: an opt-in national physician panel (Cohort A), clinicians from an integrated health system (Cohort B), and clinicians from a rural accountable care organization (Cohort C). The survey, informed by formative patient and physician focus groups conducted in 2021, assessed current and desired competence, attitudes, confidence, perceived forces for change, and barriers to obesity care. Analyses were descriptive (means and standard deviations). Results Across cohorts, desired competence exceeded current competence. The largest gaps involved recommending behavioral interventions, developing comprehensive care plans, and providing ongoing obesity management support. Attitudes toward obesity care were generally favorable, while confidence that current practices reflected best practice was only moderate. Professional and personal forces for change were moderate, patient driven motivators were moderate to high, whereas social (peer/organizational) reinforcement was weak. Reported barriers extended beyond knowledge deficits to include patient engagement, competing demands, cost, and practical constraints. Conclusions At the threshold of the GLP1 era, primary care clinicians were motivated to improve obesity care but lacked consistent support to deliver comprehensive management. The relative absence of peer and organizational reinforcement suggests that readiness for change reflected not only individual knowledge and attitudes, but also the degree of peer and organizational reinforcement that supports comprehensive obesity care in routine practice.

Background. Poor sleep quality is common in people with multiple sclerosis (pwMS) and reduces quality of life. Objectives. To examine associations between modifiable factors and sleep quality in pwMS. Methods. In a prospective clinic cohort (2017-2023), we evaluated whether baseline measures of disability, depression, fatigue, and pain were associated with poor sleep quality (Pittsburgh Sleep Quality Index, PSQI) cross-sectionally using covariate-adjusted linear regression, structural equation modeling (SEM), and LASSO logistic regression, and longitudinally using mixed-effects models. Results. In this cohort (n=750; mean age 48.9 years; 80.3% women, 88.7% relapsing type), higher body mass index ({beta} [95% CI]: 0.06 [0.01, 0.12], p=.001) and area deprivation index (6.78 [2.17, 11.39], p<.001) were associated with worse baseline PSQI scores. In adjusted analyses (n=730), disability, depression, fatigue, and pain were each associated with worse sleep. In SEM, pain had a moderate direct effect on sleep ({beta} [95% CI]: 0.56 [0.48, 0.64], p<.001). LASSO models that included pain outperformed the benchmark (AUROC 0.741 vs 0.517). Longitudinally (n=382), time and higher baseline pain predicted worse sleep ({beta} [95% CI]: time in months 0.04 [0.02, 0.06], p<.001; pain 0.36 [0.31, 0.41], p<.001). Conclusion. Pain is a key, potentially modifiable driver of poor sleep quality in pwMS.

Background Physically Disabled women are less likely to access cervical screening than non-disabled women, yet little research has been conducted to understand the problems that Disabled women face or potential solutions. Methods A cross-sectional online survey was conducted with 1493 UK-based participants who identified as having a physical disability, impairment, condition, or difference that makes cervical screening difficult or impossible. Participants were presented with statements about cervical screening problems and potential solutions and asked to indicate agreement using a 5-point scale. They also provided open-ended comments. Data were analysed using descriptive statistics, multinomial logistic regression and thematic analysis. Results More than half of participants reported delaying/missing (46.8%) or never attending (8.8%) screening, with most of those (71.0% and 81.4% respectively) indicating that the main reason was disability-related factors. The highest levels of agreement for problems were for concerns about pain, embarrassment, and fear of what the test might find and for potential solutions were for having a doctor or nurse who is willing to try different solutions, discusses specific needs, and understands physical disability. Never-attendance (OR = 0.022, 95% CI 0.014, 0.035) and delaying or missing appointments, (OR = 0.057, 95% CI 0.043, 0.076) negatively predicted future screening attendance. Six themes were identified from open-ended comments, supporting and extending the quantitative findings. Conclusion Disabled women face the same problems related to cervical screening as non-disabled women and additionally face disability-specific problems. Cervical sample taker training should incorporate ways to support physically Disabled women to have equitable access to screening.

IntroductionAccess to specialist care in the Netherlands requires a general practitioner (GP) referral, yet referrals to secondary care keep rising. Triage has been proposed to manage this demand and may be relevant for internal medicine, which addresses diverse and increasingly complex conditions. This study aimed to identify the internal medicine healthcare needs which were redirected to the GP after triage and to explore the factors driving GP referral behaviour. MethodsThis multi-method study combined quantitative referral data with qualitative insights from GP focus groups. Data were extracted from a hospital in an urban region, including adults with non-acute complaints referred for outpatient consultation to internal medicine between August 2019 and July 2021. Referrals were triaged for appropriateness and redirected where possible. Focus groups explored GPs perspectives on referral practices. ResultsOf 5,826 referrals triaged, 998 (17%) were redirected to the GP with advice and guidance. Endocrinology accounted for 35% of redirected cases, followed by nephrology (8.6%). Focus groups revealed underlying drivers of referral behaviour, identifying four themes: medical factors; GP-related factors, including professional uncertainty and autonomy; patient-related factors; and external factors, such as contextual and regulatory influences. ConclusionThis study demonstrates that triage is a feasible strategy for managing referral volumes, particularly within domains such as endocrinology where many medical problems can be managed in primary care. However, referrals are shaped by more than clinical need, reflecting uncertainty, emotional considerations, patient expectations and systemic factors. Strengthened collaboration between primary and secondary care, alongside pre-referral consultation strategies, is essential to ensure appropriate, high-quality patient care.

BackgroundGroup A streptococcus (GAS) infections have been associated with neuropsychiatric disorders in epidemiologic studies and animal models, but data in US health care populations are limited. GAS is also associated with autoimmune sequelae, including acute rheumatic fever (ARF)/Sydenham chorea (SC), poststreptococcal reactive arthritis (PSRA), poststreptococcal glomerulonephritis (PSGN), and guttate psoriasis (GP). Epstein-Barr virus (EBV) has been linked to systemic lupus erythematosus (SLE) and multiple sclerosis (MS) and the complexity of these associations parallels that of GAS-associated conditions, providing a useful comparison. Objectives1) Assess the association between a positive GAS test and incident neuropsychiatric diagnoses within 1 year in a large US health care database. 2) Assess the validity of the same database in detecting well-established disease associations while avoiding false associations. Design, Setting, ParticipantsRetrospective cohort study using TriNetX data from US health care organizations. Patients with positive or negative tests were propensity score-matched (GAS cohort n=178,301; EBV cohort n=64,854). Patients with documented neuropsychiatric diagnoses prior to testing were excluded. To approximate a primary care population, inclusion required at least one well-visit. ExposuresPositive vs negative GAS test; positive vs negative EBV test (separate cohorts). Main Outcomes and ValidationsMain outcome: incident neuropsychiatric diagnoses within 1 year of GAS testing. Positive control outcomes: ARF/SC, PSRA, PSGN, and GP (for GAS cohort); SLE and MS (for EBV cohort). Negative control outcomes: conditions without known association with GAS. ResultsAfter matching, a positive GAS test was associated with attention-deficit/hyperactivity disorder (ADHD) (RR: 1.09; 95% CI: 1.03-1.15). Among established poststreptococcal conditions, only GP was associated with prior GAS (RR: 1.75; 95% CI: 1.06-2.89). Case counts were insufficient to evaluate ARF/SC, PSRA, and PSGN. Negative control outcomes showed no association. In the EBV cohort, no association was observed with SLE, and MS showed a decreased risk. Conclusions and RelevanceA positive GAS test was associated with ADHD but not with other neuropsychiatric disorders. The database detected poststreptococcal GP but did not identify most established postinfectious autoimmune associations, likely reflecting rarity, heterogeneity, and diagnostic complexity. These findings begin to describe the range of real-world health care databases to evaluate postinfectious neuropsychiatric risk.

Introduction Experiential acceptance refers to the capacity to be open to internal experiences without attempting to change or avoid them. Although acceptance is a core emotion regulation strategy within mindfulness- and acceptance-based interventions (MABIs) and a protective factor for mental health, its conceptualization and implementation remain unclear and ambiguous. The aim of this study was to clarify and develop a comprehensive model of accepting anxiety. Method Twenty-six participants from a non-clinical sample with prior experience in MABIs took part in semi-structured interviews exploring their experience of accepting anxiety. Data collection and analysis followed the principles of Grounded Theory to generate a data-driven model of the acceptance process. Results We identified a five-stage dynamic model involving distinct processes: (Stage 1) observing through the body with attentional focus on interoceptive experience; (Stage 2) identifying and acknowledging anxiety; (Stage 3) validating and normalizing the experience through validation and self-compassion; (Stage 4) not reacting characterized by decentering and nonreactivity; and (Stage 5) staying with the experience via exposure. We also identified facilitating factors that support engagement in the acceptance process. Conclusion These findings refine the understanding of acceptance as a multidimensional emotion regulation process by highlighting an active dynamic involving multiple mechanisms underlying the acceptance of anxiety. This model provides a framework for developing more targeted clinical interventions and for investigating individual and contextual variability in these subprocesses.

Background: Obesity is globally recognized as a complex, multifactorial chronic disease, with biological, psychological, environmental and behavioural factors involved in both disease pathogenesis and maintenance. Although previous group-based studies demonstrated involvement of each of these factors, there is large inter-individual variability in the factors contributing to disease development as well as intervention outcomes, causing limited translatability to the individual level. This heterogeneity in treatment effectiveness might be due to differential causal and maintenance factors of obesity. To enable the transition from a one-size-fits-all approach to a more personalized approach for individuals with overweight or obesity, this study aims to investigate if and how the degree of weight loss and changes in daily life behaviour after a combined lifestyle intervention depend on individual baseline profiles comprising of person characteristics, biological, psychological, environmental and behavioural factors. Methods: This study will include 600 individuals varying in BMI, 200 participants with a healthy BMI (18.5-24.9kg/m2), 200 with overweight (BMI 25.0-29.9kg/m2), and 200 with obesity (BMI [&ge;]30.0kg/m2). For all participants, a comprehensive individual baseline profile is created, including person characteristics, biological, psychological, environmental and behavioural factors. A clustering method is applied to identify clusters of participants with similar characteristics. Next, we examine if and how these clusters are linked to bodyweight indicators measured at baseline, and how they relate to daily lifestyle behaviour, as measured by ecological momentary assessment (EMA) using a smartphone app and sensor technology (3-week measurements). Individuals with overweight or obesity will be randomized to the intensive lifestyle intervention or a lifestyle information condition, to determine if treatment response can be predicted based on cluster characteristics, how daily lifestyle behaviour changes after an intervention, and how changes in daily lifestyle behaviour relate to treatment response. Discussion: The End of Average study aims to characterize a large set of individuals varying in body weight to predict intervention effectiveness measured as changes in body weight indicators and in daily lifestyle behaviours. If reliable predictors of treatment success can be identified, these can be applied in personalized lifestyle interventions to improve lifestyle behaviour, body weight management and overall health.