Journal of Psychosomatic Research

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.

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).

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.

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.

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.

Background: Heterogeneity in symptom presentation and treatment response in irritable bowel syndrome (IBS) remains poorly understood. The gut microbiota may contribute to this variability, but its role in shaping symptom trajectories and responses to self-management interventions is unclear. Objective: To identify symptom trajectory phenotypes and determine whether gut microbiota composition and function distinguish these phenotypes and predict multidimensional responses to pain self-management interventions in young adults with IBS. Design: Ancillary data analysis from a randomized control trial (NCT03332537). Methods: Participants with longitudinal data (n = 62) were analyzed using longitudinal k-means clustering (KML) based on trajectories of measures in IBS quality of life (QOL), Brief Pain Inventory (BPI), and psychoneurological outcomes (anxiety, applied cognition, depression, fatigue, global health, positive affect, and sleep disturbance) over 12 weeks. Baseline differences between clusters were assessed with Wilcoxon rank-sum tests, and longitudinal changes were evaluated with linear mixed models. Gut microbiota composition and predicted functional pathways were compared between phenotypes. Bayesian Additive Regression Trees (BART) models were used to identify baseline microbial taxa and pathways predictive of longitudinal changes in QOL, BPI pain interference, and severity. Results: Two distinct trajectory-defined response phenotypes were identified: a Constrained Response Phenotype (Phenotype A, n = 35) and an Adaptive Multidomain Response Phenotype (Phenotype B, n = 27). At baseline, Phenotype B showed lower pain severity and interference, but higher levels of anxiety, depression, and fatigue compared to Phenotype A. Over 12 weeks, both phenotypes showed improvements in pain outcomes (all p < 0.05), but only Phenotype B demonstrated broad improvements across psychoneurological domains and QOL (all p < 0.05). Phenotype A exhibited more limited improvements and worsening in several psychoneurological domains. Gut microbiota functional pathways differed between phenotypes, including pathways related to xenobiotic degradation, amino acid metabolism, bile secretion, and immune-related processes (all raw p < 0.05), although these did not remain significant after multiple testing correction. Machine learning models identified distinct, phenotype-specific microbial predictors of intervention response. In Phenotype A, genera such as Alistipes and Sutterella were consistently identified across models, whereas in Phenotype B, predictors included Phascolarctobacterium, Collinsella, and Parabacteroides. Functional pathways also differed between phenotypes, suggesting distinct microbiome-linked mechanisms underlying symptom trajectories and responses to pain interventions. Conclusions: Young adults with IBS exhibit distinct multidimensional response phenotypes that are associated with differential clinical and microbiome profiles. Baseline gut microbiota composition and functional capacity demonstrate phenotype-specific predictive signatures of treatment response, supporting a microbiome-informed framework for stratifying patients and advancing personalized self-management strategies in IBS.

Background Iron deficiency (ID) is a readily treatable condition once identified. Ferritin is the primary diagnostic marker, but cut-offs vary and inflammation complicates interpretation in patients with long-term conditions (LTCs). Aim To describe ferritin distribution and the prevalence of threshold-defined low ferritin in adults with and without LTCs in primary care. Design and setting Cross-sectional observational study using routinely collected electronic health records from a national primary care database in England (1st January 2015 to 31st December 2021). Method Adults with >1 ferritin test in Clinical Practice Research Datalink (CPRD) Aurum were included. LTCs were identified using validated primary-care code lists. Outcomes included ferritin distribution and threshold-defined ID prevalence using World Health Organization (WHO) (<15 ug/L; <70 ug/L if inflammation) and National Institute for Health and Care Excellence (NICE) (<30 ug/L) cut-offs, stratified by sex and, in women, by age <50 versus >=50 as a proxy for menopausal status. Results 4,489,594 individuals were included; 55% (n=2,469,882) had >1 LTC. Ferritin was lowest in women <50 and in LTCs characterised by impaired absorption or blood loss (coeliac disease, inflammatory bowel disease). Among women <50 with an LTC, 80% had ferritin <70 ug/L versus 47% <30 ug/L, leaving 33% in the 30 to 70 ug/L range potentially missed by standard cut-offs; equivalent figures were 28% in women >=50 and 17% in men. Conclusion Threshold-defined low ferritin is very common across LTCs and disproportionately affects women, particularly those under 50. Condition-specific, inflammation-adjusted ferritin thresholds may improve detection, management, and equity in primary care.

Objective: Neuropsychiatric presentations are common across neurological and mental health services but they are often inadequately covered by core clinical psychology and clinical neuropsychology training. Consequently, we aimed to identify components for a neuropsychiatry curriculum for clinical psychologists using a Delphi process. Method: We completed a three-round e-Delphi study with 19 experts (clinical psychologists, neuropsychologists, psychiatrists, neurologists, individuals with lived experience of neuropsychiatric disorders). Round 1 collected ratings on 80 syllabus items derived from textbook reviews, conference topics, and a scoping review of neuropsychiatry syllabuses. Items failing to reach consensus were refined, and new topics added via free-text suggestions. Rounds 2 and 3 repeated rating and thematic analysis, culminating in a consensus meeting where items were classified as core or supplementary. Consensus thresholds were set at mean>=2.0, mean distance from the mean<=0.2, and => 75% agreement for final decisions. Results: The process yielded 40 core and 38 supplementary syllabus items. Core topics include autoimmune and neuroinflammatory disorders, delirium, functional neurological disorders, neuropsychiatric sequelae of epilepsy, stroke, traumatic brain injury, dementia, and multidisciplinary working, among others. Supplementary items covered background knowledge of less frequent but still prevalent disorders as well as competencies in interpreting clinical data alongside conceptual and historical issues. The final component list reflects both clinical competencies and emerging areas of practice, emphasising assessment, formulation, psychological interventions, cultural considerations, and medicolegal aspects. Conclusions: The e-Delphi derived curriculum provides a framework for neuropsychiatric competencies for postgraduate psychology training with modification needed for application in diverse healthcare settings.

Background: Internet-based cognitive behavioral therapy (iCBT) is efficacious for panic disorder (PD), yet the mechanisms of change remain underspecified. Anxiety sensitivity (AS) is theoretically central to PD maintenance, but its role as a mediator has not been formally tested in Spanish-speaking populations using minimal-contact formats. This study evaluates the efficacy of the "Free from Anxiety" iCBT program and examines AS as a mediator of clinical outcomes. Methods: In a randomized controlled trial, 95 adults meeting DSM-IV-TR criteria for PD were assigned to an 8-week iCBT program with optional email support (n = 49) or a waiting-list control (n = 46). Primary outcome was PD severity (PDSS); secondary outcomes included anxiety sensitivity (ASI-3), general anxiety (BAI), and depression (BDI-II). Mediation was assessed via Baron and Kenny's framework with bootstrapping (5,000 resamples) to estimate the indirect effect of ASI-3 change on PDSS reduction. Results: The treatment group showed significant improvements across all measures compared to controls (PDSS: d = 0.76, 95% CI [0.10, 1.42]; mean d = 1.30). Mediation analysis confirmed that ASI-3 change partially mediated the treatment effect on PDSS (indirect effect = 1.85, 95% CI [0.36, 3.70]), accounting for 27.4% of the total effect. The direct effect remained significant (b = 4.89, p < .001). Intent-to-treat (ITT) analyses supported robustness (d = 0.47 to 1.47). Gains were maintained at 6-month follow-up (d = 1.19 to 1.26). Conclusions: iCBT reduces anxiety sensitivity as a partial mechanism of change, aligning with cognitive models of panic. These findings support Free from Anxiety as an evidence-based, viable first-step intervention for Spanish-speaking clinical populations within stepped-care pathways.

Background and Aims: Fatigue is a prevalent and disabling symptom in inflammatory bowel disease (IBD), yet its underlying biological mechanisms remain poorly understood. We aimed to characterize fatigue-associated molecular signatures in IBD patients by integrating DNA methylation and mRNA expression analyses. Methods: Peripheral blood was collected from 40 patients with Crohn's disease (CD), 29 with ulcerative colitis (UC), and 10 healthy controls. Fatigue severity was assessed continuously using the Multidimensional Fatigue Inventory (MFI). Epigenome-wide DNA methylation profiling and mRNA sequencing were performed, identifying differentially methylated regions (DMRs) and differentially expressed genes (DEGs) for active and quiescent CD and UC, adjusting for age, sex, and smoking status. Pathway enrichment analysis was performed on genes with differential methylation and expression. Results: In active CD, more severe fatigue was associated with transcriptional suppression of immune and metabolic pathways (246 DMRs; 1,090 DEGs), versus upregulation of mitochondrial and metabolic processes in quiescent CD (200 DMRs; 1,619 DEGs). In active UC, fatigue was associated with anabolic pathway upregulation and epigenetic silencing of neuroactive pathways (6,927 DMRs; 343 DEGs; 56 concordant genes). Quiescent UC showed transcriptional changes without significant epigenetic pathway enrichment (1,710 DMRs; 3,224 DEGs). Healthy controls exhibited a distinct profile spanning metabolic, immune, and neuronal pathways (8,621 DMRs; 395 DEGs). Fatigue-associated signatures were largely non-overlapping across all five groups. Conclusions: Fatigue-associated molecular profiles differed substantially by disease subtype and activity state, highlighting the biological heterogeneity of IBD-related fatigue and laying the foundation for multi-omics approaches to identify biomarkers and potential therapeutic targets.

Introduction: Hypertension is the world's leading cause of death, and depression its leading cause of disability. Control rates for these noncommunicable diseases (NCDs) are low in low and middle-income countries (LMICs). Many LMICs have programs to screen and treat underserved communities for infectious diseases, but evidence to adapt them to treat NCDs is limited. We developed and tested a non-communicable disease program through Ghana's Community-Based Health Planning and Services (CHPS) primary care initiative. Methods: We trained 8 CHPS nurses to diagnose and treat hypertension and depression through door-to-door screening and pharmacotherapy. Physician assistants provided telehealth supervision. We combined this treatment with volunteer counseling to boost medication adherence, improve mood, and change health behaviors. We called the 90-day intervention the CHPS Opportunity for Mentally and Behaviorally Integrated NCD Engagement (COMBINE). Results: We recruited 60 adults from 580 screened: 37 with hypertension (mean blood pressure (BP) of 149/91 mm Hg) and 23 with depression (mean physician health questionnaire (PHQ-9) score of 13.3). After 90 days, 57/60 (95%) completed the intervention: 32/37 (86%) achieved blood pressure control (mean BP 122/75 mm Hg), and 19 of 20 (95%) achieved depression control (mean PHQ-9 score 2.0). After 12 months, 51/60 were retained: 33/37 with hypertension (89%) and 18/23 with depression (78%), with a mean BP of 121/75 and PHQ-9 score of 1.4 respectively. All 51 (100%) achieved disease control at 12 months. 5 persons left by migration and 4 by escalation to higher-level care. Conclusions: The COMBINE model achieved high levels of diagnosis, care retention, and disease control, with minimal adverse events, in a remote setting with limited usual NCD care. This model suggests a novel means to improve the care cascade for these and other noncommunicable diseases through existing non-physician care models in LMICs, warranting further controlled testing at scale.

Background. Lifetime exposure to trauma is associated with chronic pain. Separate studies of chronic pain and trauma report overlapping alterations in white matter microstructure, yet their distinct and cumulative effects remain unclear. Methods. White matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) from the UK Biobank (N = 21,995) were analysed using linear mixed-effects models. First, group effects (chronic pain versus control) on white matter integrity within this cohort were established. To investigate distinct and cumulative impacts of trauma exposure at different developmental stages, main and interactive effects of group and trauma severity on FA and MD were examined in separate groups exposed to childhood maltreatment only, adulthood trauma only, and both. Sex-stratified analyses were conducted. Results. Chronic pain was associated with widespread alterations and was spatially refined to brainstem tracts and cingulum when accounting for maltreatment/trauma severity. Accounting for chronic pain, cumulative trauma severity was associated with alterations in brainstem, frontal and parietal tracts, whereas adulthood trauma showed comparable but attenuated patterns. Childhood maltreatment severity was associated with localised FA and MD reductions in brainstem tracts, sagittal stratum and superior longitudinal fasciculus. These effects were more pronounced in females than males. A chronic pain-by-maltreatment/trauma severity interaction was observed for FA in the superior cerebellar peduncle in females exposed to childhood maltreatment only. Conclusions. Distinct and interactive effects of chronic pain and maltreatment/trauma severity on white matter microstructure were evident. The findings suggest that trauma-informed care should be tailored by timing of exposure and sex in this population.

Importance: As new treatments increase quality and length of life in people with multiple sclerosis (MS), effective prevention and management of common comorbidities, including Diabetes Mellitus (DM), is increasingly important. Objective: To compare incidence of DM and its associations with hospitalisation and mortality in adults with MS and matched controls. Design: Using English primary care data from the Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics and national mortality records, we matched adults with MS diagnosed between 2000 and 2023, with up to ten controls without MS by age, sex, and practice. We excluded individuals with preexisting DM, defined using diagnostic and management codes. Outcomes included all-cause hospitalisation (number and duration) and mortality. We used Poisson, negative binomial, linear, and Cox proportional hazards models, adjusting for demographic and socioeconomic factors, adding interaction terms to examine if ethnicity, deprivation, and urbanity were associated with outcomes. Results: We included 9,010 individuals with MS and 78,121 matched controls. Over a mean follow-up of 13.2 years, people with MS had over twice the incidence of DM compared with controls (adjusted incidence rate ratio [aIRR]=2.26, 95% CI: 1.96 to 2.61, p<0.001). Among people with MS, incident DM was associated with higher hospitalisation rates (aIRR=1.82, 95%CI: 1.47 to 2.28, p<0.001), longer hospitalisation duration (median 18 vs 4 days, adjusted beta;=0.53, 95%CI: 0.41 to 0.65, p<0.001), and increased all-cause mortality when incident DM was modelled as a time-varying exposure (adjusted hazard ratio=1.46, 95%CI: 1.17 to 1.82, p<0.001), compared to those who did not develop DM. Similar patterns were observed among controls (hospitalisation rates: aIRR = 2.96, 95% CI 2.63 to 3.23, p<0.001; hospitalisation duration: adjusted {beta} = 0.93, 95% CI: 0.86 to 0.99, p<0.001; mortality [time-varying]: HR = 1.50, 95% CI: 1.27 to 1.77, p<0.001). The relationship between DM and increased hospitalisation was stronger in rural areas among those with MS and stronger in White groups among controls. Conclusions: People with MS are more likely to be diagnosed with DM, resulting in greater all-cause hospitalisation and all-cause mortality. This highlights the importance of equitable screening, prevention, and management of DM in people living with MS, with particular attention to geographical health inequalities.

Multimorbidity, the co-existence of two or more long-term conditions, is up to three times more prevalent among people with cancer than in the general population and is associated with poorer survival, particularly for cancers with a more favourable prognosis such as colorectal cancer. In Scotland, multimorbidity is the norm among older adults, emerges earlier in socioeconomically deprived populations, and may contribute to comparatively low cancer survival rates. Despite this, the influence of multimorbidity on the colorectal cancer pathway remains poorly understood. We conducted a Scottish data-linkage study of adults diagnosed with colorectal cancer between 2010 and 2014, linking the Scottish Cancer Registry to national prescribing, hospital admissions, death registration, and bowel screening datasets. Prescribing data were used to derive overall and system-specific comorbidity measures as a proxy for multimorbidity and active disease burden. Associations with stage at diagnosis, treatment, survival, and screening uptake were examined using logistic regression and Cox proportional hazards models adjusted for demographic and clinical covariates. Among 19,043 patients, 87% had at least one prescribing-based comorbidity, most commonly cardiovascular, nervous system, and gastrointestinal conditions. Overall comorbidity burden was not associated with stage at diagnosis, although laxative-related prescribing was associated with later-stage disease. Increasing comorbidity burden reduced the likelihood of receiving any treatment and surgery, while associations varied across system-specific comorbidities. Higher comorbidity burden was also associated with increased all-cause and colorectal cancer-specific mortality, particularly among patients with respiratory, nervous system, and haematological/nutritional conditions. Screening uptake was not associated with overall comorbidity burden but did differ by system-specific comorbidity. Prescribing-based multimorbidity was highly prevalent and strongly associated with treatment patterns and mortality among patients with colorectal cancer. System-specific multimorbidity measures provided greater discrimination than overall morbidity counts, highlighting the importance of considering distinct multimorbidity profiles when assessing cancer pathways and designing targeted interventions for optimising treatment and survival. Keywords (primary health care, general practice, multimorbidity, comorbidity, colorectal cancer, early diagnosis, cancer treatment, survival)

Background: Individuals diagnosed with depression during pregnancy are more likely to develop cardiovascular disease (CVD) later in life. However, it remains unclear whether subclinical depressive symptoms or symptom trajectories across time are associated with indicators of cardiovascular health (CVH). Therefore, the present study evaluated the relationship between longitudinal depressive symptom trajectories beginning in pregnancy and future CVH. Methods: This secondary analysis of the multisite prospective nuMoM2b-Heart Health Study and included participants with complete longitudinal data from early pregnancy to 2-7 years post-delivery. Participants self-reported depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) at 6-13 weeks gestation (early pregnancy), 22-29 weeks gestation (mid- to late-pregnancy), and 2-7 years post-delivery. Latent class mixture modeling was conducted to identify longitudinal patterns of depressive symptoms across early pregnancy, mid-late pregnancy, and extended postpartum follow-up. Structural equation modeling was used to test whether EPDS trajectories were associated with latent CVH, adjusted for length of follow-up interval, pre-pregnancy BMI, gravidity, adverse pregnancy outcomes, smoking history, age, education, income, and use of psychiatric medications. Results: A total of 3,934 participants (mean (M) {+/-} standard deviation (SD) age=27.6{+/-}5.6 years) met inclusion criteria with a mean follow-up interval of 3.2{+/-}0.9 years. A 4-class model, which provided the best fit to the EPDS data (mean posterior probability across classes=0.81), produced the following trajectories: (1) stable low (n=2412; 61.1%), (2) increasing severity (n=848; 21.5%), (3) decreasing severity (n=476; 12.1%), and (4) stable high (n=212; 5.4%). Compared to the stable low group, all groups exhibited significantly lower CVH (stable high: {beta}=0.06, p<0.01; decreasing severity: {beta}=0.05, p=0.02; increasing severity: {beta}=0.08 p<0.01). Pairwise comparisons among the three elevated-symptom groups revealed no significant differences in latent CVH (all ps >0.24). Discussion: The longitudinal course of depressive symptoms from pregnancy to 2-7 years post-delivery varied across individuals. Compared to those with consistently low depressive symptoms, individuals with higher severity symptoms at any point all exhibited lower CVH, regardless of the specific trajectory of symptoms. These findings support a life-course perspective in which depressive symptom patterns may represent an early indicator of cardiometabolic vulnerability.

Depression is accompanied by considerable comorbidity and excess mortality. We examined multimorbidity data using the validated pharmacy-based Rx-Risk Comorbidity Index and examined healthcare costs associated with chronic illness burden in the Australian Genetics of Depression Study (AGDS). Australian Pharmaceutical Benefits Scheme (PBS) record linkage for 15,890 AGDS participants was available from 01/07/2013-31/12/2017. Forty-six health morbidities were inferred by mapping the prescription data using Anatomical Therapeutic Chemical Classification System codes and PBS Item Codes. Morbidity prevalence rates were then compared with an unselected 10% Australian representative population sample (10PCT) with PBS claims data available from 01/07/2010-31/12/2014. The average number of inferred comorbidities was higher among AGDS participants (4.6 {+/-} 2.9) than 10PCT individuals (3.0 {+/-} 3.0). Excluding depression, 89.1% of AGDS participants had one or more inferred comorbidity, most commonly pain (51.0%), inflammation/pain (40.3%), and anxiety (32.3%). In the AGDS, the number of comorbidities was higher among women compared to men and positively correlated with participant age, BMI, number of depressive episodes experienced, and annual health care costs. Compared to participants with no inferred comorbidities, the median annual health care costs were ~65% higher among those with 2-3 comorbidities. This study highlights the patterns of health morbidities experienced by individuals living with depression and shows that this chronic disease burden is significantly associated with increased health costs to the individual and the health system.

Purpose In deprescribing studies, a prescription-free gap is typically used to determine if patients discontinued their treatment. An appropriate gap depends on the typical time between prescriptions during continued use. This work aims to characterise the interval between prescriptions of chronic drugs using different methods for a cohort of older people in primary care in Ireland. Methods The empirical prescription interval was analysed for 38,154 patients for the twenty most common drug classes and the association between covariates and the interval was analysed using a multi-level model. Estimates were also compared to those obtained from the parametric waiting time distribution (pWTD) approach. Results Available covariates had consistent relationships with prescription intervals across drug classes. For example, each additional prescription issue was associated with an increase in the interval by 5.0 (NSAIDs) to 19.7 days ("Other antidepressants"). Full public health cover was associated with a -29.0 day (inhaled adrenergics) to -11.0 day (opioids) change relative to partial cover, while other/private cover had a -17.9 day (benzodiazepines and associated drugs) to -7.1 day (SSRI and SNRIs) change relative to partial cover. The pWTD also produced consistent estimates of the population interval for most drugs. Conclusions The interval varied substantially within drug classes, due to a mixture of patient, practice and unmodelled factors. Variation between practices was effectively explained, with residual variation between patients and within patients. The pWTD approach is useful for describing complex distributions of intervals, and may be more appropriate for inferring a gap than summarising truncated data.

Introduction Functional neurological disorder (FND) is a common cause of neurological disability and is associated with substantial healthcare utilisation and cost. Most available treatments target specific symptom subtypes, and prospective evidence regarding the effect of treatment on health-system costs remains limited. We evaluated the real-world clinical and economic outcomes of a transdiagnostic outpatient intervention, attention-based rehabilitation (ABR). Methods We conducted a pragmatic waitlist-controlled study in 54 consecutively referred patients with neurologist-diagnosed FND attending a specialist outpatient service. Clinical outcomes--including quality of life (Short Form-36), social and occupational participation (Work and Social Adjustment Scale), symptom severity, and mental health (Hospital Anxiety and Depression Scale)--were assessed at waitlist entry, treatment commencement, treatment completion, and 6 and 12 months post-treatment. Healthcare utilisation and costs were obtained prospectively from health-service financial records for the 6 months preceding treatment, the treatment period, and two consecutive 6-month post-treatment periods. Longitudinal clinical outcomes and healthcare costs were analysed using Bayesian mixed-effects and mixture models, respectively. Results All clinical measures remained stable or worsened during the waitlist control period. Across treatment, six of eight SF-36 domains, WSAS, employment status, and both HADS subdomains improved, with maintenance through 12 months. Patient-reported symptom improvement persisted post-treatment. Expected monthly health system costs approximately halved post-treatment, with net cost savings by approximately 50 days. Conclusion A fixed-duration, symptom-agnostic outpatient ABR programme was associated with durable improvements in functioning and quality of life, alongside substantial reductions in healthcare utilisation and cost, supporting scalable symptom-agnostic treatment models for FND.

Background: Dissociative experiences encompass a variety of discontinuities in awareness and perception that are elevated in the dissociative disorders and associated with extensive comorbid symptomatology. Accumulating evidence points to developmental trauma and trait responsiveness to verbal suggestions (REVS) as factors that confer risk for severe dissociative symptoms, but they have typically been studied in isolation. This study integrated these measures using prediction modelling to better understand their predictive value for the risk of dissociative psychopathology. Method: 1,104 non-clinical participants completed measures of trauma, dissociation and trait REVS. The predictive model was developed using elastic net logistic regression, internally validated with 10-fold cross-validation, and assessed using receiver operating characteristic (ROC) curve and area under the ROC (AUROC). Variables entered into the model were components of REVS, trauma, age, and their interactions. Results: A dissociative psychopathology at-risk group (7%) was characterised by younger age, greater trauma and elevated REVS, particularly involuntariness during cognitive-perceptual suggestions. The prediction model retained nine of ten predictors, with an AUROC of .77 [95% CI: .73, .82], reflecting good discrimination with moderate sensitivity (78%) but modest specificity (67%). Conclusions: These findings reinforce trauma and trait REVS as risk factors for dissociative psychopathology and demonstrate that they can be integrated in a model that can identify at-risk individuals. Further validation and extension of the model is necessary to improve the identification of individuals at risk for severe dissociative symptomatology and the diagnosis of dissociative disorders with implications for outcome trajectories.