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Background: We aimed to identify and characterise the longitudinal patterns of multimorbidity associated with stroke. Methods: We used an unsupervised patient-oriented clustering approach to analyse primary care electronic health records (EHR) of 30 common long-term conditions (LTC) in patients with stroke aged over 18, registered in 41 general practices in south London between 2005 and 2021. Results: Of 849,968 registered patients, 9,847 (1.16%) had a record of stroke and 46.5% were female. The median age at record of stroke was 65.0 year (IQR: 51.5-77.0) and the median number of LTCs in addition to stroke was 3 (IQR: 2-5). We identified eight clusters of multimorbidity with contrasted socio-demographic characteristics (age, gender, and ethnicity) and risk factors. Beside a core of 3 clusters associated with conventional stroke risk-factors, minor clusters exhibited less common combinations of LTCs including mental health conditions, asthma, osteoarthritis and sickle cell anaemia. Importantly, complex profiles combining mental health conditions, infectious diseases and substance dependency emerged. Conclusion: This novel longitudinal and patient-oriented perspective on multimorbidity addresses existing gaps in mapping the patterns of stroke-associated multimorbidity not only in terms of LTCs, but also socio-demographic characteristics, and suggests potential for more efficient and patient-oriented healthcare models. [ABSTRACT FROM AUTHOR]

Background: Existing estimates of palliative care need in the UK were produced before the COVID-19 pandemic. We sought to produce updated, population-level estimates of palliative care need for each of the four UK nations and explore how these changed during the pandemic. Methods: We conducted a descriptive analysis of routine data. We used a well-established, diagnosis-based methodology which produced minimal estimates of palliative care need based on underlying causes of death; intermediate estimates based on underlying and contributory causes of death; and maximal estimates based on excluding unexpected causes of death. Additional estimates incorporated deaths involving COVID-19. All methods were applied to official mortality statistics from England, Wales, Scotland, and Northern Ireland for the years 2017 to 2021. Results: From 2017 to 2019 for the UK in total, palliative care need was estimated at ~ 74% (minimal), ~ 90% (intermediate) and ~ 96% (maximal) of total deaths, which was broadly consistent with previous studies. Results were similar across all nations. In the pandemic years, 2020-21, the minimal estimates remained stable in terms of the number of people in need but dropped significantly in terms of the proportion of deaths associated with palliative care need (to ~ 66%) due to the overall increase in mortality and large number of deaths from COVID-19. The intermediate (~ 90%) and maximal (~ 96%) estimates showed an increase in the number of people in need but remained stable in proportion of deaths. When deaths involving COVID-19 were treated as deaths associated with palliative need, the minimal estimates increased to ~ 77% and intermediate estimates increased to ~ 92%. Conclusions: In each of the UK's nations, most people who die will have palliative care needs. Excluding deaths from COVID-19 in population-level estimates of palliative care need risks under-estimating true levels of need. Future studies which estimate population-level palliative care need should consider factoring in deaths from COVID-19. [ABSTRACT FROM AUTHOR]

Background: Family carers of people living with comorbid dementia and cancer (CDC) play a vital supportive role, but this may be particularly burdensome and adversely impact their own health and wellbeing. Objective: To examine the experiences and psychosocial support needs of caregivers of people with CDC. Methods: A flyer advertising the study was distributed to relevant UK voluntary sector organisations and shared across social media. 13 carers of people with CDC were recruited. In-depth semi-structured interviews were conducted and transcripts were analysed using reflexive thematic analysis, underpinned by an inductive phenomenological approach. Results: Complex interactions of dementia and cancer resulted in heightened responsibility for carers, who played a crucial role in recognition/management of symptoms, performing difficult cancer-related care, and treatment decision-making that posed difficult ethical challenges. Care-recipients had reduced insight into their cancer diagnosis and prognosis, so carers often carried the emotional burden alone. Responsibilities faced by carers were compounded by a lack of targeted, accessible information/support for CDC. Carers expressed a desire to talk to and learn from others who understand the unique challenges of navigating cancer-related decision-making, treatment and care for people who are also living with dementia. Conclusions: Cancer alongside dementia presents complex challenges for carers, who desire more cancer-related information and support which is tailored to people living with dementia and their family caregivers. [ABSTRACT FROM AUTHOR]

Background: The number of individuals living with multiple (≥2) long term conditions (MLTCs) is a growing global challenge. People with MLTCs experience reduced life expectancy, complex healthcare needs, higher healthcare utilisation, increased burden of treatment, poorer quality of life and higher mortality. Evolving technologies including artificial intelligence (AI) could address some of these challenges by enabling more preventive and better integrated care, however, they may also exacerbate inequities. Objective: We aim to deliver an equity focused, action-ready plan for transforming MLTC prevention and care, co-designed by people with lived experience of MLTCs and delivered through an Innovation Hub: SysteMatic. Design: Our Hub is being co-designed by people with lived experience of MLTCs, practitioners, academics and industry partners in Liverpool and Glasgow, UK. This work builds on research into mental-physical health interdependence across the life-course, and on mobilisation of large-scale quantitative data and technology validation in health and care systems serving deprived populations in Glasgow and Liverpool. We work with 3 population segments: 1) Children & Families: facing psychosocial and environmental challenges with lifetime impacts; 2). Working Life: people with poorly integrated mental, physical and social care; and 3) Pre-Frailty: older people with MLTCs. We aim to understand their experiences and in parallel look at routinely collected health data on people with MLTCs to help us identify targets for intervention. We are co-identifying opportunities for systems transformation with our patient partners, healthcare professionals and through discussion with companies and public-sector organisations. We are co-defining 3/5/7-year MLTC innovation/transition targets and sustainable learning approaches. Discussion: SysteMatic will deliver an actionable MLTC Innovation Hub strategic plan, with investment from the UK National Health Service, civic health and care partners, universities, and industry, enabling feedback of well-translated, patient and public prioritised problems into the engineering, physical, health and social sciences to underpin future equitable innovation delivery. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the depot‐ and sex‐specific associations of adiposity indicators with incident multimorbidity and comorbidity pairs. Materials and Methods: We selected 382 678 adults without multimorbidity (≥2 chronic diseases) at baseline from the UK Biobank. General obesity, abdominal obesity and body fat percentage indices were measured. Results: Cox proportional hazard regression analyses of general obesity indices revealed that for every one‐unit increase in body mass index, the risk of incident multimorbidity increased by 5.2% (95% confidence interval 5.0%‐5.4%). A dose‐response relationship was observed between general obesity degrees and incident multimorbidity. The analysis of abdominal obesity indices showed that for every 0.1 increment in waist‐to‐height ratio and waist‐to‐hip ratio, the risk of incident multimorbidity increased by 42.0% (37.9%‐46.2%) and 27.9% (25.7%‐30.0%), respectively. Central obesity, as defined by waist circumference, contributed to a 23.2% increased risk of incident multimorbidity. Hip circumference and hip‐to‐height ratio had protective effects on multimorbidity onset. Consistent findings were observed for males and females. Body fat percentage elevated 3% (0.2%‐5.9%) and 5.3% (1.1%‐9.7%) risks of incident multimorbidity in all adults and females, respectively. Arm fat percentages elevated 5.3% (0.8%‐9.9%) and 19.4% (11.0%‐28.5%) risks of incident multimorbidity in all adults and males, respectively. The general obesity indices, waist circumference, waist‐to‐height ratio, waist‐to‐hip ratio and central obesity increased the onset of comorbidity pairs, whereas hip circumference and hip‐to‐height ratio decreased the onset of comorbidity pairs. These adiposity indicators mainly affect diabetes mellitus‐related comorbidity onset in males and hypertensive‐related comorbidity onset in females. Conclusions: Adiposity indicators are predictors of multimorbidity and comorbidity pairs and represent a promising approach for intervention. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity, known as the co-occurrence of at least two chronic conditions, has become of increasing concern in the current context of ageing populations, though it affects all ages. Early life risk factors of multimorbidity include adverse childhood experiences (ACEs), particularly associated with psychological conditions and weight problems. Few studies have considered related mechanisms and focus on old age participants. We are interested in estimating, from young adulthood, the risk of overweight-depression comorbidity related to ACEs while adjusting for early life confounders and intermediate variables. Methods: We used data from the 1958 National Child Development Study, a prospective birth cohort study (N = 18 558). A four-category outcome (no condition, overweight only, depression only and, overweight-depression comorbidity) was constructed at 23, 33, and 42 years. Multinomial logistic regression models adjusting for intermediate variables co-occurring with this outcome were created. ACEs and sex interaction on comorbidity risk was tested. Results: In our study sample (N = 7762), we found that ACEs were associated with overweight-depression comorbidity risk throughout adulthood (RRR [95% CI] at 23y = 3.80 [2.10–6.88]) though less overtime. Comorbidity risk was larger than risk of separate conditions. Intermediate variables explained part of the association. After full-adjustment, an association remained (RRR [95% CI] at 23y = 2.00 [1.08–3.72]). Comorbidity risk related to ACEs differed by sex at 42. Conclusion: Our study provides evidence on the link and potential mechanisms between ACEs and the co-occurrence of mental and physical diseases throughout the life-course. We suggest addressing ACEs in intervention strategies and public policies to go beyond single disease prevention. [ABSTRACT FROM AUTHOR]

Introduction: Over a fifth of pregnant women are living with multiple long‐term health conditions, which is associated with increased risks of adverse outcomes for mothers and infants. While there are many examples of research exploring individuals' experiences and care pathways for pregnancy with a single health condition, evidence relating to multiple health conditions is limited. This study aimed to explore experiences and care of women with multiple long‐term health conditions around the time of pregnancy. Methods: Semistructured interviews were conducted between March 2022 and May 2023 with women with multiple long‐term health conditions who were at least 28 weeks pregnant or had had a baby in the last 2 years, and healthcare professionals with experience of caring for these women. Participants were recruited from across the United Kingdom. Data were analysed using thematic analysis. Results: Fifty‐seven women and 51 healthcare professionals participated. Five themes were identified. Women with long‐term health conditions and professionals recognised that it takes a team to avoid inconsistent care and communication, for example, medication management. Often, women were required to take a care navigation role to link up their healthcare providers. Women described mixed experiences regarding care for their multiple identities and the whole person. Postnatally, women and professionals recognised a downgrade in care, particularly for women's long‐term health conditions. Some professionals detailed the importance of engaging with women's knowledge, and recognising their own professional boundaries of expertise. Many participants described difficulties in providing informational continuity and subsequent impacts on care. Specifically, the setup of care systems made it difficult for everyone to access necessary information, especially when care involved multiple sites. Conclusion: Pregnant women with long‐term health conditions can experience a substantial burden of responsibility to maintain communication with their care team, often feeling vulnerable, patronised, and let down by a lack of acknowledgement of their expertise. These results will be used to inform the content of coproduction workshops aimed at developing a list of care recommendations for affected women. It will also inform future interventional studies aimed at improving outcomes for these women and their babies. Patient or Public Contribution: Our Patient and Public Involvement group were involved in the design of the study and the analysis and interpretation of the data, and a public study investigator was part of the author group. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.g. Parkinson's disease, vascular disease), in others, conditions may reflect a prodromal stage of dementia (e.g. depression, anxiety and psychosis). Aims: To assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy. Method: We examined ante-mortem and autopsy data from 767 brain tissue donors from the UK, identifying physical multimorbidity in later life and specific brain-related conditions. We assessed associations between these purported risk factors and dementia-related neuropathological changes at autopsy (Alzheimer's-disease related neuropathology, Lewy body pathology, cerebrovascular disease and limbic-predominant age-related TDP-43 encephalopathy) with logistic models. Results: Physical multimorbidity was not associated with greater dementia-related neuropathological changes. In the presence of physical multimorbidity, clinical dementia was less likely to be associated with Alzheimer's disease pathology. Conversely, conditions which may be clinical or prodromal manifestations of dementia-related neuropathology (Parkinson's disease, cerebrovascular disease, depression and other psychiatric conditions) were associated with dementia and neuropathological changes. Conclusions: Physical multimorbidity alone is not associated with greater dementia-related neuropathological change; inappropriate inclusion of brain-related conditions in multimorbidity measures and misdiagnosis of neurodegenerative dementia may better explain increased rates of clinical dementia in multimorbidity [ABSTRACT FROM AUTHOR]

Background and objectives People with parkinsonism who are older, living in a care home, with frailty, multimorbidity or impaired capacity to consent are under-represented in research, limiting its generalisability. We aimed to evaluate more inclusive recruitment strategies. Methods From one UK centre, we invited people with parkinsonism to participate in a cross-sectional study. Postal invitations were followed by telephone reminders and additional support to facilitate participation. Personal consultees provided information on the views regarding research participation of adults with impaired capacity. These approaches were evaluated: (i) using external data from the Parkinson's Real World Impact assesSMent (PRISM) study and Clinical Practice Research Datalink (CPRD), a sample of all cases in UK primary care, and (ii) comparing those recruited with or without intensive engagement. Results We approached 1,032 eligible patients, of whom 542 (53%) consented and 477 (46%) returned questionnaires. The gender ratio in PRIME-UK (65% male) closely matched CPRD (61% male), unlike in the PRISM sample (46%). Mean age of PRIME participants was 75.9 (SD 8.5) years, compared to 75.3 (9.5) and 65.4 (8.9) years for CPRD and PRISM, respectively. More intensive engagement enhanced recruitment of women (13.3%; 95% CI 3.8, 22.9%; P  = 0.005), care home residents (6.2%; 1.1, 11.2%; P  = 0.004), patients diagnosed with atypical parkinsonism (13.7%; 5.4, 19.9%; P  < 0.001), and those with a higher frailty score (mean score 0.2, 0.1, 0.2; P  < 0.001). Conclusions These recruitment strategies resulted in a less biased and more representative sample, with greater inclusion of older people with more complex parkinsonism. [ABSTRACT FROM AUTHOR]

Background The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. Methods We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. Results Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5–6, patients with multimorbidity and a lifestyle score of 0–1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5–6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5–6 to 0–1. And we observed more pronounced association between them among people younger than 60 years old. Conclusions Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity. [ABSTRACT FROM AUTHOR]

Introduction: Those with severe and enduring mental ill health are at greater risk of long‐term physical health conditions and have a reduced life expectancy as a result. Multiple factors compound this health inequality, and the need for setting research priorities in this area is highlighted with physical and mental healthcare services being separate, and limited multimorbidity research. Methods: The aim of this exercise was to work in partnership with healthcare professionals and carers, family, friends and individuals with lived experience of both mental and physical health conditions, to set research priorities to help people with mental health conditions to look after their physical health. The exercise was guided by the James Lind Alliance approach. For this, a steering group was set up, two surveys were completed and a final priority workshop was conducted. Results: This priority setting exercise guided by people's needs and lived experience has produced a set of well‐defined research topics. Initially, 555 research questions were suggested in the first survey, which were refined to 54 questions for the second survey. A priority setting workshop was then conducted to get the final 10 priorities. Conclusions: Taking these topics forward to improve services and treatment for both mental and physical ill health may in turn improve physical health and lessen the reduced life expectancy of those living with mental ill health. Patient or Public Contribution: This work was completed in collaboration with people who have lived experience of mental ill health and physical health conditions, as well as carers, family and friends. Their contribution has been significant for this work from piloting surveys, amending language used and educating the researchers and contributing to this paper. The initial work was completed with a steering group and continued with surveys and workshops. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort. Methods: The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions. Results: For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66–0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68–0.70) and 0.89 (0.88–0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63–0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis. Conclusions: In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to co-develop a Frailty, Health and Care Needs Assessment (FHCNA) questionnaire for people experiencing homelessness and explore the feasibility of its use by non-clinical staff in homeless hostels. Design/methodology/approach: The FHCNA, aimed at identifying frailty and other health and care priorities for people experiencing homelessness, was co-designed in workshops (online and in person) with homelessness and inclusion health staff. Its feasibility was tested by staff and their clients in two hostels, with pre- and post-study focus groups held with hostel staff to gain input and feedback. Findings: The FHCNA was co-developed and then used to collect 74 pairs of resident and key worker inputted data (62% of eligible hostel residents). The mean age of clients was 48 years (range 22–82 years). High levels of unmet need were identified. Over half (53%) were identified as frail. Common concerns included difficulty walking (46%), frequent falls (43%), chronic pain (36%), mental health issues (57%) and dental concerns (50%). In total, 59% of clients reported difficulty in performing at least one basic activity of daily living, while only 14% had undergone a Care Act Assessment. Hostel staff found using the FHCNA to be feasible, acceptable and potentially useful in facilitating explorations of met and unmet health and social care needs of hostel clients. By identifying unmet needs, the FHCNA has the potential to support staff to advocate for access to health and social care support. Originality/value: To the best of the authors' knowledge, this is the first study to co-develop and feasibility test a questionnaire for use by non-clinically trained staff to identify frailty and other health and care needs of people experiencing homelessness in a hostel setting. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK). Methods: We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40–59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network. Results: We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients. Conclusions: Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK. [ABSTRACT FROM AUTHOR]

Background: Patients with unmet healthcare needs are more likely to access unscheduled care. Identifying these patients through data-driven and clinical risk stratification for active case management in primary care can help address patient need and reduce demand on acute services. Aim: To determine how a proactive digital healthcare system can be used to undertake comprehensive needs analysis of patients at risk of unplanned admission and mortality. Design & setting: Prospective cohort study of six general practices in a deprived UK city. Method: To identify those with unmet needs, the study's population underwent digitally-driven risk stratification into Escalated and Non-escalated groups using seven risk factors. The Escalated group underwent further stratification using GP clinical assessment into Concern and No concern groups. The Concern group underwent Unmet Needs Analysis (UNA). Results: From 24 746 patients, 516 (2.1%) were triaged into the Concern group and 164 (0.7%) underwent UNA. These patients were more likely to be older (t = 4.69, P<0.001), female (X2 = 4.46, P<0.05), have a Patients At Risk of Re-hospitalisation (PARR) score ≥80 (X2 = 4.31, P<0.05), be a nursing home resident (X2 = 6.75, P<0.01), or on an end-of-life (EOL) register (X2 = 14.55, P<0.001). Following UNA, 143 (87.2%) patients had further review planned or were referred for further input. The majority of patients had four domains of need. In those who GPs would not be surprised if they died within the next few months, n = 69 (42.1%) were not on an EOL register. Conclusion: This study showed how an integrated, patient-centred, digital care system working with GPs can highlight and implement resources to address the escalating care needs of complex individuals. [ABSTRACT FROM AUTHOR]

Background: Healthcare workers' (HCW) well-being has a direct effect on patient care. However, little is known about the prevalence and patterns of long-term medical conditions in HCWs, especially those from ethnic minorities. This study evaluated the burden of multiple long-term conditions (MLTCs), i.e. the presence of two or more single long-term conditions (LTCs), among HCWs in the United Kingdom (UK) and variation by ethnicity and migration status. Methods: We used baseline data from the UK-REACH cohort study collected December 2020–March 2021. We used multivariable logistic regression, adjusting for demographic, occupational and lifestyle factors to examine the relationship between self-reported LTCs/MLTCs and ethnicity, migration status and time since migration to the UK. Results: Of 12,100 included HCWs, with a median age of 45 years (IQR: 34–54), 27% were overseas-born, and 30% were from non-White ethnic groups (19% Asian, 4% Black, 4% Mixed, 2% Other). The most common self-reported LTCs were anxiety (14.9%), asthma (12.2%), depression (10.7%), hypertension (8.7%) and diabetes (4.0%). Mental health conditions were more prevalent among UK-born than overseas-born HCWs for all ethnic groups (adjusted odds ratio (aOR) using White UK-born as the reference group each time: White overseas-born 0.77, 95%CI 0.66–0.95 for anxiety). Diabetes and hypertension were more common among Asian (e.g. Asian overseas, diabetes aOR 2.97, 95%CI 2.30–3.83) and Black (e.g. Black UK-born, hypertension aOR 1.77, 95%CI 1.05–2.99) groups than White UK-born. After adjustment for age, sex and deprivation, the odds of reporting MLTCs were lower in most ethnic minority groups and lowest for those born overseas, compared to White UK-born (e.g. White overseas-born, aOR 0.68, 95%CI 0.55–0.83; Asian overseas-born aOR 0.75, 95%CI 0.62–0.90; Black overseas-born aOR 0.52, 95%CI 0.36–0.74). The odds of MLTCs in overseas-born HCWs were equivalent to the UK-born population in those who had settled in the UK for ≥ 20 years (aOR 1.14, 95%CI 0.94–1.37). Conclusions: Among UK HCWs, the prevalence of common LTCs and odds of reporting MLTCs varied by ethnicity and migrant status. The lower odds of MLTCs in migrant HCWs reverted to the odds of MLTCs in UK-born HCWs over time. Further research on this population should include longitudinal studies with linkage to healthcare records. Interventions should be co-developed with HCWs from different ethnic and migrant groups focussed upon patterns of conditions prevalent in specific HCW subgroups to reduce the overall burden of LTCs/MLTCs. [ABSTRACT FROM AUTHOR]

Background: Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer. Methods: This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI). Results: In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m2) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m2) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09–0.47). Conclusions: Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population. [ABSTRACT FROM AUTHOR]

Background: The co-occurrence of cardiometabolic diseases (CMDs) is increasingly prevalent and has been associated with an additive risk of dementia in older adults, but the extent to which this risk can be offset by a healthy lifestyle is unknown. We aimed to examine the associations of cardiometabolic multimorbidity and lifestyle with incident dementia and related brain structural changes. Methods: This prospective study extracted health and lifestyle data from 171 538 UK Biobank participants aged 60 years or older without dementia at baseline between 2006 and 2010 and followed up until July 2021, as well as brain structural data in a nested imaging subsample of 11 972 participants. Cardiometabolic multimorbidity was defined as the presence of two or more CMDs among type 2 diabetes, coronary heart disease, stroke, and hypertension. Lifestyle patterns were determined based on 7 modifiable lifestyle factors including smoking, alcohol consumption, physical activity, diet, sleep duration, sedentary behavior, and social contact. Results: Over a median follow-up of 12.3 years, 4479 (2.6%) participants developed dementia. The presence of CMDs was dose-dependently associated with an increased risk of dementia. Compared with participants with no CMDs and a favourable lifestyle, those with ≥ 3 CMDs and an unfavourable lifestyle had a five times greater risk of developing dementia (HR 5.33, 95% CI 4.26–6.66). A significant interaction was found between CMD status and lifestyle (Pinteraction=0.001). The absolute difference in incidence rates of dementia per 1000 person years comparing favourable versus unfavourable lifestyle was − 0.65 (95% CI − 1.02 to − 0.27) among participants with no CMDs and − 5.64 (− 8.11 to − 3.17) among participants with ≥ 3 CMDs, corresponding to a HR of 0.71 (0.58–0.88) and 0.42 (0.28–0.63), respectively. In the imaging subsample, a favourable lifestyle was associated with larger total brain, grey matter, and hippocampus volumes across CMD status. Conclusion: Our findings suggest that adherence to a healthy lifestyle might substantially attenuate dementia risk and adverse brain structural changes associated with cardiometabolic multimorbidity. [ABSTRACT FROM AUTHOR]

Background The burden of chronic conditions associated with sugary beverages is increasing but little is known about the role of different types of sugary beverages in the co-occurrence of multiple chronic conditions ('multimorbidity'). To inform future sugar-reduction guidelines, we aimed to examine the associations of sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB) and natural juices (NJ) with multimorbidity. Methods This prospective cohort study included 184 093 UK Biobank participants aged 40–69 years at baseline who completed at least one occasion of 24-h dietary recall between 2009 and 2012. Daily consumptions of SSB, ASB and NJ were assessed using 24-h dietary recall. Participants were followed from the first 24-h assessment until the onset of two or more new chronic conditions, or the end of follow-up (31 March 2017), whichever occurred first. Logistic regression models, Cox proportional hazard models and quasi-Poisson mixed effects models were used to estimate the association of beverages intakes with chronic conditions and multimorbidity. Results A total of 19 057 participants had multimorbidity at baseline and 19 968 participants developed at least two chronic conditions during follow-up. We observed dose–response relationships of SSB and ASB consumptions with the prevalence and incidence of multimorbidity. For example, the adjusted hazard ratios (HRs) and 95% CIs of the incidence of developing at least two chronic conditions ranged from 1.08 (1.01–1.14) for SSB intake of 1.1–2 units/day to 1.23 (1.14–1.32) for >2 units/day compared with 0 units/day. Also, the adjusted HRs (95% CIs) of ASB consumption ranged from 1.08 (1.03–1.13) for 0.1–1 unit/day to 1.28 (1.17–1.40) for >2 units/day compared with non-consumers. Conversely, moderate consumption of NJ was associated with a smaller risk of the prevalence and incidence of multimorbidity. Moreover, higher intakes of SSB and ASB were positively associated whereas moderate intake of NJ was inversely associated with increased number of new-onset chronic conditions during follow-up. Conclusions Higher SSB and ASB intakes were positively associated whereas moderate NJ intake was inversely associated with the higher risk of multimorbidity and increased number of chronic conditions. Current and intended policy options to decrease the burden of chronic conditions and multimorbidity need a formulation of SSB and ASB reduction strategies. [ABSTRACT FROM AUTHOR]

Background: Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity. Methods: We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations. Results: Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs. Conclusions: Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group. [ABSTRACT FROM AUTHOR]

Background: Maternal multiple long-term conditions are associated with adverse outcomes for mother and child. We conducted a qualitative study to inform a core outcome set for studies of pregnant women with multiple long-term conditions. Methods: Women with two or more pre-existing long-term physical or mental health conditions, who had been pregnant in the last five years or planning a pregnancy, their partners and health care professionals were eligible. Recruitment was through social media, patients and health care professionals' organisations and personal contacts. Participants who contacted the study team were purposively sampled for maximum variation. Three virtual focus groups were conducted from December 2021 to March 2022 in the United Kingdom: (i) health care professionals (n = 8), (ii) women with multiple long-term conditions (n = 6), and (iii) women with multiple long-term conditions (n = 6) and partners (n = 2). There was representation from women with 20 different physical health conditions and four mental health conditions; health care professionals from obstetrics, obstetric/maternal medicine, midwifery, neonatology, perinatal psychiatry, and general practice. Participants were asked what outcomes should be reported in all studies of pregnant women with multiple long-term conditions. Inductive thematic analysis was conducted. Outcomes identified in the focus groups were mapped to those identified in a systematic literature search in the core outcome set development. Results: The focus groups identified 63 outcomes, including maternal (n = 43), children's (n = 16) and health care utilisation (n = 4) outcomes. Twenty-eight outcomes were new when mapped to the systematic literature search. Outcomes considered important were generally similar across stakeholder groups. Women emphasised outcomes related to care processes, such as information sharing when transitioning between health care teams and stages of pregnancy (continuity of care). Both women and partners wanted to be involved in care decisions and to feel informed of the risks to the pregnancy and baby. Health care professionals additionally prioritised non-clinical outcomes, including quality of life and financial implications for the women; and longer-term outcomes, such as children's developmental outcomes. Conclusions: The findings will inform the design of a core outcome set. Participants' experiences provided useful insights of how maternity care for pregnant women with multiple long-term conditions can be improved. [ABSTRACT FROM AUTHOR]

Background: The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy. Methods: A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy. Results: During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14–1.18) and 1.55 (1.53–1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33–2.47), 1.71 (1.65–1.76), 1.41 (1.35–1.47) and 1.39 (1.30–1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18–1.20) and 1.05 (1.03–1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy. Conclusions: The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus. [ABSTRACT FROM AUTHOR]

Background: Numerous approaches are used to characterise multiple long‐term conditions (MLTC), including counts and indices. Few studies have compared approaches within the same dataset. We aimed to characterise MLTC using simple approaches, and compare their prevalence estimates of MLTC and associations with emergency hospital admission in the UK Biobank. Methods: We used baseline data from 495,465 participants (age 38–73 years) to characterise MLTC using four approaches: Charlson index (CI), Byles index (BI), count of 43 conditions (CC) and count of body systems affected (BC). We defined MLTC as more than two conditions using CI, BI and CC, and more than two body systems using BC. We categorised scores (incorporating weightings for the indices) from each approach as 0, 1, 2 and 3+. We used linked hospital episode statistics and performed survival analyses to test associations with an endpoint of emergency hospital admission or death over 5 years. Results: The prevalence of MLTC was 44% (BC), 33% (CC), 6% (BI) and 2% (CI). Higher scores using all approaches were associated with greater outcome rates independent of sex and age group. For example, using CC, compared with score 0, score 2 had 1.95 (95% CI: 1.91, 1.99) and a score of 3+ had 3.12 (95% CI: 3.06, 3.18) times greater outcome rates. The discriminant value of all approaches was modest (C‐statistics 0.60–0.63). Conclusions: The counts classified a greater proportion as having MLTC than the indices, highlighting that prevalence estimates of MLTC vary depending on the approach. All approaches had strong statistical associations with emergency hospital admission but a modest ability to identify individuals at risk. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to classify individuals with RA and =2 additional long-term conditions (LTCs) and describe the association between different LTC classes, number of LTCs and adverse health outcomes. Methods: We used UK Biobank participants who reported RA (n=5,625) and employed latent class analysis (LCA) to create classes of LTC combinations for those with =2 additional LTCs. Cox-proportional hazard and negative binomial regression were used to compare the risk of all-cause mortality, major adverse cardiac events (MACE), and number of emergency hospitalisations over an 11-year follow-up across the different LTC classes and in those with RA plus one additional LTC. Persons with RA without LTCs were the reference group. Analyses were adjusted for demographic characteristics, smoking, BMI, alcohol consumption and physical activity. Results: A total of 2,566 (46%) participants reported =2 LTCs in addition to RA. This involved 1,138 distinct LTC combinations of which 86% were reported by =2 individuals. LCA identified 5 morbidity-classes. The distinctive condition in the class with the highest mortality was cancer (class 5; HR 2.66 95%CI (1.91-3.70)). The highest MACE (HR 2.95 95%CI (2.11-4.14)) and emergency hospitalisations (rate ratio 3.01 (2.56-3.54)) were observed in class 3 which comprised asthma, COPD & CHD. There was an increase in mortality, MACE and emergency hospital admissions within each class as the number of LTCs increased. Conclusions: The risk of adverse health outcomes in RA varied with different patterns of multimorbidity. The pattern of multimorbidity should be considered in risk assessment and formulating management plans in patients with RA. [ABSTRACT FROM AUTHOR]

Objective: Physical activity has protective effects on cardiometabolic diseases (CMDs), but the role of metabolism related to physical activity in this process is unclear., Methods: In the prospective cohort study from UK Biobank between 2006 and 2022, participants free of CMDs at baseline were included (n = 73,990). We identified physical activity-related metabolites and constructed metabolic signature using linear regression and elastic net regression. Association between physical activity, metabolic signature, and CMDs (type 2 diabetes [T2D], coronary heart disease [CHD], and stroke) were explored using Cox and mediation analyses. Interactions between the metabolic signature and genetic susceptibility (categorized into "low" and "high" based on the median of polygenic risk scores) were assessed by additive hazard models and relative excess risk due to interaction (RERI). Multi-state models evaluated the association between metabolic signature and disease progression., Results: We found 58 metabolites were related to physical activity, of which 17 were used to construct metabolic signature. The metabolic signature was associated with reduced risk of T2D (HR = 0.13[0.10-0.16]), CHD (HR = 0.40[0.34-0.47]), and stroke (HR = 0.67[0.53-0.86]), and mediated 40.56 % of the association between physical activity and T2D. The metabolic signature exhibited additive interactions with genetic risk for T2D (RERI = 1.57[1.09-2.05]) and CHD (RERI = 0.27[0.05-0.49]). Finally, the metabolic signature was associated with a reduced risk of transition from CMD to CMM (HR = 0.58[0.42-0.81])., Conclusion: Physical activity-related metabolic signature is linked to reduced risks of CMDs and CMM. We once again emphasize the importance of physical activity for CMDs prevention from a metabolic perspective, especially for individuals at high genetic risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Maternal short-term outcomes of postpartum depression (PPD) were widely examined, but little is known about its long-term association with multiple chronic diseases (multimorbidity) in women's later life. This study aims to assess the association of PPD with chronic diseases and multimorbidity in women's mid-late life., Methods: This prospective cohort study included female participants in UK Biobank who attended online follow-up assessment and reported their history of PPD. A total of 36 chronic diseases were assessed and multimorbidity was defined as the co-existence of two or more of these diseases. Participants were followed from the baseline recruitment to the onset of two or more chronic diseases, death, or the end of follow-up (2023). Logistic regression models, Cox proportional hazard models, quasi-Poisson mixed effects models, and linear mixed models were conducted to examine the association of PPD with chronic diseases and multimorbidity at baseline and during follow-up., Results: Among all 54,885 participants, 5106 (9.3%) participants experienced PPD, 13,928 (25.4%) participants had multimorbidity at baseline, and 14,135 (25.8%) participants developed two or more diseases during a median follow-up of 15 years. Women with a PPD history had higher odds of having multimorbidity at baseline (odds ratio = 1.35, 95% confidence interval [CI] = 1.27-1.44) and higher risk of developing multimorbidity during follow-up (hazard ratio = 1.13, 95% CI = 1.08-1.20). PPD was associated with increased number of chronic diseases, with the relatively new-onset number of diseases during follow-up being 8% higher for those with PPD (relative risk = 1.08, 95% CI = 1.05-1.12). Chronic diseases also accumulated at a faster annual rate for women with a history of PPD (b = 0.009, 95% CI = 0.007-0.011), compared to those without. We observed no interaction or mediation effects of physical activity, smoking, alcohol drinking, and dietary factors on the association between PPD and multimorbidity; however, women's body mass index at baseline contributed to the association, with the mediation proportion of 6.38% (2.56-10.20%)., Conclusions: PPD was associated with higher risks of chronic diseases and multimorbidity in women's mid-late life. This finding supports the importance of perinatal and postpartum mental health care, and its role in the prevention of chronic diseases and multimorbidity throughout women's life course., Competing Interests: Declarations. Ethics approval and consent to participate: The UK Biobank has ethical approval from the North West Multi-centre Research Ethics Committee (reference number 06/MRE08/65). All participants provided informed consent. Institutional review board approval was exempted for this study because of the publicly available and deidentified data. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Identifying clusters of multiple long-term conditions (MLTCs), also known as multimorbidity, and their associated burden may facilitate the development of effective and cost-effective targeted healthcare strategies. This study aimed to identify clusters of MLTCs and their associations with long-term health-related quality of life (HRQoL) in two UK population-based cohorts., Methods: Age-stratified clusters of MLTCs were identified at baseline in UK Biobank (n = 502,363, 54.6% female) and UKHLS (n = 49,186, 54.8% female) using latent class analysis (LCA). LCA was applied to people who self-reported ≥ 2 LTCs (from n = 43 LTCs [UK Biobank], n = 13 LTCs [UKHLS]) at baseline, across four age-strata: 18-36, 37-54, 55-73, and 74 + years. Associations between MLTC clusters and HRQoL were investigated using tobit regression and compared to associations between MLTC counts and HRQoL. For HRQoL, we extracted EQ-5D index data from UK Biobank. In UKHLS, SF-12 data were extracted and mapped to EQ-5D index scores using a standard preference-based algorithm. HRQoL data were collected at median 5 (UKHLS) and 10 (UK Biobank) years follow-up. Analyses were adjusted for available sociodemographic and lifestyle covariates., Results: LCA identified 9 MLTC clusters in UK Biobank and 15 MLTC clusters in UKHLS. Clusters centred around pulmonary and cardiometabolic LTCs were common across all age groups. Hypertension was prominent across clusters in all ages, while depression featured in younger groups and painful conditions/arthritis were common in clusters from middle-age onwards. MLTC clusters showed different associations with HRQoL. In UK Biobank, clusters with high prevalence of painful conditions were consistently associated with the largest deficits in HRQoL. In UKHLS, clusters of cardiometabolic disease had the lowest HRQoL. Notably, negative associations between MLTC clusters containing painful conditions and HRQoL remained significant even after adjusting for number of LTCs., Conclusions: While higher LTC counts remain important, we have shown that MLTC cluster types also have an impact on HRQoL. Health service delivery planning and future intervention design and risk assessment of people with MLTCs should consider both LTC counts and MLTC clusters to better meet the needs of specific populations., Competing Interests: Declarations. Ethics approval and consent to participate: All participants gave informed consent to data provision. UK Biobank has full ethical approval from the NHS National Research Ethics Service (16/NW/0274). The University of Essex Ethics Committee has approved all data collection on UKHLS main study and innovation panel waves. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background and Aims: Previous observational studies have investigated the association between coffee consumption and single cardiometabolic disease. Yet, the extent to which coffee might confer health advantages to individuals with a singular cardiometabolic disease remains unclear. This study aimed to further investigate the association of coffee consumption and the onset and progression from single cardiometabolic disease to cardiometabolic multimorbidity (CMM)., Methods and Results: This prospective cohort study included 185,112 participants from the UK Biobank who were enrolled between 2006 and 2010 and followed up until 2020. Coffee consumption was collected using a 24-h dietary questionnaire. CMM was defined as the coexistence of at least two cardiometabolic diseases, including type 2 diabetes (T2D), coronary heart disease (CHD) and stroke. Cox proportional hazards and multi-state models estimated the associations between coffee consumption and CMM. During a median follow-up of 11.4 years, 1585 participants developed CMM. Compared with nonconsumers, coffee consumers had lower risks for the transitions from baseline to single cardiometabolic disease, with the respective lowest hazard ratios and 95% confidence intervals (CIs) for the transitions from baseline to T2D, CHD and stroke after multivariable adjustment being 0.79 (CI, 0.72-0.87), 0.91 (CI, 0.86-0.97) and 0.87 (CI, 0.78-0.96). Coffee consumption resulted in a significant reduction in the risk of the transitions from CHD and stroke to CMM, with the lowest estimates were 0.56 (CI, 0.43-0.73) and 0.60 (CI, 0.43-0.83). Similar associations were observed in unsweetened coffee. Sugar-sweetened coffee was associated with some transitions at low levels of consumption. The associations between artificially sweetened coffee and CMM were less consistent., Conclusions: Coffee consumption was associated with lower risk for almost all transition phases of CMM development and consistent findings were observed with unsweetened coffee., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Cardiometabolic multimorbidity (CMM), defined as the co-occurrence of 2 or more cardiometabolic diseases, including myocardial infarction (MI), stroke, and type 2 diabetes (T2D), is an increasing public health challenge. Although poor diet is a known risk factor for a first cardiometabolic disease (FCMD), the relationship with subsequent occurrence of CMM is less studied., Objectives: This study aims to investigate the prospective association between baseline adherence to the Mediterranean diet and the onset of CMM across various follow-up durations., Methods: We used data from the European Prospective Investigation into Cancer-Norfolk cohort study of 21,900 adults, aged 40-79 free of prevalent MI, stroke, and T2D at baseline (1993-1997). A median-based Mediterranean diet score and a pyramid-based MDS (pyr-MDS) were used to measure baseline adherence to the Mediterranean diet. Multistate modeling was employed to investigate associations with the FCMD and the subsequent CMM event., Results: Over the entire follow-up period of 21.4 y (median), we observed 5028 FCMD and 734 CMM events. Multistate analysis indicated that the association between baseline Mediterranean diet and the risk of CMM may be stronger in shorter follow-up durations. Particularly, baseline pyr-MDS was significantly associated with the risk of subsequent CMM transitioning from FCMD when follow-up durations were limited to 10 and 15 y, with hazard ratio (95% confidence interval) being 0.67 (0.53, 0.84) and 0.80 (0.70, 0.92) per SD increase in pyr-MDS, respectively. Additionally, we observed that the risk of CMM transitioning from FCMD was modified by social class across shorter to longer follow-ups, where the impact of baseline Mediterranean diet was only significant in nonmanual workers., Conclusions: Baseline adherence to the Mediterranean diet was potentially associated with a lower risk of CMM transitioning from FCMD, particularly during shorter follow-up periods., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: This study aims to evaluate the impact of ultra-processed food (UPF) on type 2 diabetes (T2D), cardiovascular disease (CVD), hypertension, and cardiometabolic multimorbidity (CMM), and to explore the role of genetic susceptibility in these associations., Methods and Results: 90 631 participants from the UK Biobank were included (collected between 2006 and 2010). The outcomes assessed included T2D, CVD, hypertension and CMM. The Cox proportional hazards model was used to evaluate their associations and the potential modification by genetic risk, which was estimated using the polygenic risk score (PRS). Participants with high UPF consumption had a higher risk of T2D, CVD, and CMM, with the adjusted hazard ratio (HR) of 1.36 (95 % confidence interval [CI]: 1.15, 1.61), 1.13 (95%CI: 1.03, 1.23), and 1.14 (95%CI: 1.05, 1.24), respectively. Those with high UPF consumption and high PRS for T2D, CVD, and hypertension had the highest risk of T2D (HR: 4.01; 95%CI: 2.83, 5.69), CVD (HR: 2.18; 95%CI: 1.86, 2.56), and hypertension (HR: 1.79; 95%CI: 1.61, 1.99), respectively. In participants with one cardiometabolic disease (CMD), those with high UPF consumption and high PRS T2D or PRS CVD had the highest risk of developing CMM. A significant additive interaction was observed between PRS T2D and UPF consumption on the risk of T2D., Conclusion: Our study underscored the importance of identifying individuals with high UPF consumption for targeted dietary interventions to mitigate the risk of CMDs and CMM, particularly among those with a high genetic risk of CMDs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives Control of disease activity in RA is a crucial part of its management to prevent long-term joint damage and disability. This study aimed to identify early predictors of poor disease activity at 5 and 10 years, focusing on comorbidities and clinical/sociodemographic factors at first presentation. Methods Patients from two UK-based RA cohorts were classified into two groups; low (<3.2) and moderate/high (≥3.2) DAS using 28 joint counts (DAS28) at 5/10 years. Clinical variables (e.g. rheumatoid nodules, erosions), sociodemographic factors (e.g. ethnicity, deprivation) and comorbidities were recorded at baseline and yearly thereafter. The Rheumatic Diseases Comorbidity Index quantified patient comorbidity burden. Binary logistic regression models (outcome low vs moderate/high DAS28) were fitted using multiple imputation. Results A total of 2701 patients living with RA were recruited (mean age 56.1 years, 66.9% female); 5-year data were available for 1718 (63.4%) patients and 10-year data for 820 (30.4%). Baseline Rheumatic Diseases Comorbidity Index was not associated with DAS28 at 5 [odds ratio (OR) 1.05, 95% CI 0.91, 1.22] or 10 years (OR 0.99, 95% CI 0.75, 1.31) in multivariable analyses. Sociodemographic factors (female gender, worse deprivation) and poorer baseline HAQ-Disability Index were associated with DAS28 ≥3.2 at both timepoints. Being seropositive was associated with 5-year DAS28 ≥3.2. Conclusion This study demonstrates an association between sociodemographic and clinical factors and long-term RA disease activity, in models adjusting for comorbidity burden. The findings call for more holistic and targeted patient management in patients with RA and provide insights for more individualized management plans even on first presentation to rheumatology. [ABSTRACT FROM AUTHOR]

Multimorbidity generally refers to concurrent occurrence of multiple chronic conditions. These patients are inherently at high risk and often lead a poor quality of life due to delayed treatments. With the emergence of personalized medicine and stratified healthcare, there is a need to stratify patients right at the primary care setting. Here we developed multimorbidity analysis pipeline (MulMorPip), which can stratify patients into multimorbid subgroups or endotypes based on their lifetime disease diagnosis and characterize them based on demographic features and underlying disease–disease interaction networks. By implementing MulMorPip on UK Biobank cohort, we report five distinct molecular subclasses or endotypes of multimorbidity. For each patient, we calculated the existence of broad disease classes defined by Charlson's comorbidity classification using the International Classification of Diseases-10 encoding. We then applied multiple correspondence analysis in 77 524 patients from UK Biobank, who had multimorbidity of more than one disease, which resulted in five multimorbid clusters. We further validated these clusters using machine learning and were able to classify 20% model-blind test set patients with an accuracy of 97% and an average Jaccard similarity of 84%. This was followed by demographic characterization and development of interlinking disease network for each cluster to understand disease–disease interactions. Our identified five endotypes of multimorbidity draw attention to dementia, stroke and paralysis as important drivers of multimorbidity stratification. Inclusion of such patient stratification at the primary care setting can help general practitioners to better observe patients' multiple chronic conditions, their risk stratification and personalization of treatment strategies. [ABSTRACT FROM AUTHOR]

Identification of shared causal genes between dementia and its related clinical outcomes can help understand shared aetiology and multimorbidity surrounding dementia. We performed the HyPrColoc colocalization analysis to detect possible shared causal genes between dementia or Alzheimer's disease (AD) and 5 selected traits: stroke, diabetes, atherosclerosis, cholesterol level, and alcohol consumption within 601 dementia or AD associated genetic regions using summary results of the UK Biobank genome-wide association studies. Functional analysis was performed on the candidate causal genes to explore potential biological pathways. Rs150562240 in the LPIN3 gene was identified as a candidate shared causal variant across dementia, AD and atherosclerosis. Evidence for pairwise colocalization between dementia and stroke, dementia (or AD) and atherosclerosis, and dementia (or AD) and diabetes was found in 2, 6 and 2 genetic regions respectively. Colocalization signals between diabetes and the other 3 non-dementia/AD traits were detected in 5 regions. The colocalization evidence shown in our study suggested shared aetiology between dementia and related diseases such as stroke, atherosclerosis, and diabetes. [ABSTRACT FROM AUTHOR]

Background: People with severe mental illness (SMI), such as schizophrenia, have higher rates of physical long-term conditions (LTCs), poorer health outcomes, and shorter life expectancy compared with the general population. Previous research exploring SMI and diabetes highlights that people with SMI experience barriers to self-management, a key component of care in long-term conditions; however, this has not been investigated in the context of other LTCs. The aim of this study was to explore the lived experience of co-existing SMI and LTCs for service users, carers, and healthcare professionals. Methods: A qualitative study with people with SMI and LTCs, their carers, and healthcare professionals, using semi-structured interviews, focused observations, and focus groups across the UK. Forty-one interviews and five focus groups were conducted between December 2018 and April 2019. Transcripts were coded by two authors and analysed thematically. Results: Three themes were identified, 1) the precarious nature of living with SMI, 2) the circularity of life with SMI and LTCs, and 3) the constellation of support for self-management. People with co-existing SMI and LTCs often experience substantial difficulties with self-management of their health due to the competing demands of their psychiatric symptoms and treatment, social circumstances, and access to support. Multiple long-term conditions add to the burden of self-management. Social support, alongside person-centred professional care, is a key facilitator for managing health. An integrated approach to both mental and physical healthcare was suggested to meet service user and carer needs. Conclusion: The demands of living with SMI present a substantial barrier to self-management for multiple co-existing LTCs. It is important that people with SMI can access person-centred, tailored support for their LTCs that takes into consideration individual circumstances and priorities. [ABSTRACT FROM AUTHOR]

Background: Opioid prescribing has more than doubled in the UK between 1998 and 2016. Potential adverse health implications include dependency, falls and increased health expenditure. Aim: To describe the predictors of long‐term opioid prescribing (LTOP) (≥3 opioid prescriptions in a 90‐day period). Design and setting: A retrospective cross‐sectional study in 41 general practices in South London. Method: Multi‐level multivariable logistic regression to investigate the determinants of LTOP. Results: Out of 320 639 registered patients ≥18 years, 2679 (0.8%) were identified as having LTOP. Patients were most likely to have LTOP if they had ≥5 long‐term conditions (LTCs) (adjusted odds ratio [AOR] 36.5, 95% confidence interval [CI] 30.4‐43.8) or 2‐4 LTCs (AOR 13.8, CI 11.9‐16.1) in comparison to no LTCs, were ≥75 years compared to 18‐24 years (AOR 12.31, CI 7.1‐21.5), were smokers compared to nonsmokers (AOR 2.2, CI 2.0‐2.5), were female rather than male (AOR 1.9, CI 1.7‐2.0) and in the most deprived deprivation quintile (AOR 1.6, CI 1.4‐1.8) compared to the least deprived. In a separate model examining individual LTCs, the strongest associations for LTOP were noted for sickle cell disease (SCD) (AOR 18.4, CI 12.8‐26.4), osteoarthritis (AOR 3.0, CI 2.8‐3.3), rheumatoid arthritis (AOR 2.8, CI 2.2‐3.4), depression (AOR 2.6, CI 2.3‐2.8) and multiple sclerosis (OR 2.5, CI 1.4‐4.4). Conclusion: LTOP was significantly higher in those aged ≥75 years, with multimorbidity or specific LTCs: SCD, osteoarthritis, rheumatoid arthritis, depression and multiple sclerosis. These characteristics may enable the design of targeted interventions to reduce LTOP. [ABSTRACT FROM AUTHOR]

Exploring multimorbidity relationships among diseases is of great importance for understanding their shared mechanisms, precise diagnosis and treatment. However, the landscape of multimorbidities is still far from complete due to the complex nature of multimorbidity. Although various types of biological data, such as biomolecules and clinical symptoms, have been used to identify multimorbidities, the population phenotype information (e.g. physical activity and diet) remains less explored for multimorbidity. Here, we present a graph convolutional network (GCN) model, named MorbidGCN, for multimorbidity prediction by integrating population phenotypes and disease network. Specifically, MorbidGCN treats the multimorbidity prediction as a missing link prediction problem in the disease network, where a novel feature selection method is embedded to select important phenotypes. Benchmarking results on two large-scale multimorbidity data sets, i.e. the UK Biobank (UKB) and Human Disease Network (HuDiNe) data sets, demonstrate that MorbidGCN outperforms other competitive methods. With MorbidGCN, 9742 and 14 010 novel multimorbidities are identified in the UKB and HuDiNe data sets, respectively. Moreover, we notice that the selected phenotypes that are generally differentially distributed between multimorbidity patients and single-disease patients can help interpret multimorbidities and show potential for prognosis of multimorbidities. [ABSTRACT FROM AUTHOR]

Background: The distinct and combined impacts of subjective well-being (SWB) and objective well-being (OWB) on cardiometabolic diseases and cardiometabolic multimorbidity remain largely unknown., Methods: 141,086 participants (mean age 56 years) were included from the UK Biobank study from 2006 to 2010. The SWB included happiness and life satisfaction. The OWB represents the level of satisfaction with objective conditions which was created using latent class analysis. Cardiometabolic diseases comprise diabetes and cardiovascular disease, including coronary heath disease and stroke. The Cox models were used to estimate the hazard ratio (HR) and 95 % confidence intervals (95 % CI) of the individual and combined associations between SWB and OWB with the risk of cardiometabolic diseases., Results: During a median follow-up of 12 years (1,693,800 person-years), 16,678 new-onset cardiometabolic diseases were reported. In full-adjusted model, the HR (95 % CI) among men with high SWB was 0.93 (0.82-1.05), 0.85 (0.79-0.92) and 0.71 (0.57-0.87), for diabetes, cardiovascular disease, and cardiometabolic multimorbidity, compared to low SWB, respectively. Among women with high SWB, the HR (95 % CI) was 0.71 (0.62-0.81), 0.76 (0.69-0.83) and 0.55 (0.42-0.72) for diabetes, cardiovascular disease and cardiometabolic multimorbidity, respectively. Low OWB increases the cardiometabolic diseases risk by from 16 % to 103 %. Notably, high SWB was associated with lower cardiometabolic diseases risk among individuals with low OWB., Limitations: Potential recall bias and residual confounding are the main limitations., Conclusions: We found that both high SWB and OWB were significantly associated with a lower risk of cardiometabolic diseases, more evident among women. The association between SWB and cardiometabolic diseases was independent of OWB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Research on sickness absence has typically focussed on single diagnoses, despite increasing recognition that long-term health conditions are highly multimorbid and clusters comprising coexisting mental and physical conditions are associated with poorer clinical and functional outcomes. The digitisation of sickness certification in the UK offers an opportunity to address sickness absence in a large primary care population. Methods: Lambeth Datanet is a primary care database which collects individual-level data on general practitioner consultations, prescriptions, Quality and Outcomes Framework diagnostic data, sickness certification (fit note receipt) and demographic information (including age, gender, self-identified ethnicity, and truncated postcode). We analysed 326 415 people's records covering a 40-month period from January 2014 to April 2017. Results: We found significant variation in multimorbidity by demographic variables, most notably by self-defined ethnicity. Multimorbid health conditions were associated with increased fit note receipt. Comorbid depression had the largest impact on first fit note receipt, more than any other comorbid diagnoses. Highest rates of first fit note receipt after adjustment for demographics were for comorbid epilepsy and rheumatoid arthritis (HR 4.69; 95% CI 1.73–12.68), followed by epilepsy and depression (HR 4.19; 95% CI 3.60–4.87), chronic pain and depression (HR 4.14; 95% CI 3.69–4.65), cardiac condition and depression (HR 4.08; 95% CI 3.36–4.95). Conclusions: Our results show striking variation in multimorbid conditions by gender, deprivation and ethnicity, and highlight the importance of multimorbidity, in particular comorbid depression, as a leading cause of disability among working-age adults. [ABSTRACT FROM AUTHOR]

Objectives Evidence suggests that factors beyond disease activity associate with functional disability in RA. The primary study objective was to explore associations between comorbidities, sociodemographic factors and functional outcomes at five and 10 years. Methods RA patients from two UK prospective cohorts were grouped into low (<1.5) and high (≥1.5) five- and 10-year health assessment questionnaire (HAQ) score. Clinical variables (e.g. disease activity, rheumatoid nodules, erosions) and sociodemographic factors (e.g. ethnicity, deprivation) were recorded at baseline and yearly thereafter. Comorbidity was measured using the Rheumatic Diseases Comorbidity Index (RDCI). Binary logistic regression models were fitted using multiple imputation. Results In total, 2701 RA patients were recruited (mean age 56.1 years, 66.9% female). A total of 1718 (63.4%) had five-year and 820 (30.4%) 10-year follow-up data. In multivariable analysis, no association was found between RDCI and HAQ ≥ 1.5 at five or 10 years. Sociodemographic factors (increased age at disease onset, female gender, minority ethnicity) were associated with higher odds of HAQ ≥ 1.5 at five and 10 years, with worse deprivation additionally associated with HAQ ≥ 1.5 at 10 years (OR 0.79, 95% CI: 0.69, 0.90). Conclusion Comorbidities at baseline have not been found to be associated with worse RA functional outcome in the long-term. On the other hand, sociodemographic factors, independently of disease measures, are associated with worse functional outcome in RA at five and 10 years, in models adjusting for comorbidity burden. Tailoring management interventions according to not only clinical disease parameters but also patient sociodemographic factors may improve long-term outcomes including functional disability. [ABSTRACT FROM AUTHOR]

Background: While the TyG index has been studied in relation to stroke risk, there is a lack of research integrating fat distribution indicators like Body Roundness Index (BRI) and Fat Mass Index (FMI). Additionally, comparative studies across multiple regions are scarce. This study investigates the association between obesity-related parameters and stroke incidence, examining the mediation effects of multimorbidity, using data from rural areas in China and the United Kingdom., Methods: This cohort study included 60,685 participants (6,980 from China and 53,705 from UK). The obesity-related parameters were calculated using established formulas. The TyG index was determined as ln [TG (mg/dL) × GLU (mg/dL) / 2]. Additionally, composite indices were created by multiplying the TyG index by BMI, WC, FMI, and RBI to assess obesity-related risks. Cox regression analyses were employed on the relationship between Triglyceride Glucose index related parameters and stroke risk. Multiple mediation analysis was applied to assess the contributions of multimorbidity to obesity indicators in stroke occurrence., Results: After excluding those who developed stroke within two years of enrollment, the Chinese cohort (6,638 subjects, median follow-up 4.33 years) had 237 ischemic and 21 hemorrhagic strokes. The UK cohort (53,631 subjects, median follow-up 13.85 years) had 742 ischemic and 316 hemorrhagic strokes. Chinese residents had lower BMI but higher visceral obesity (BRI), higher prevalence of multimorbidity, and higher stroke incidence compared to UK residents. Cox analyses demonstrated significant associations between BMI/TyG indices and ischemic stroke in both Chinese and UK populations, which diminished after adjusting for multimorbidity. In the Chinese rural cohort, only TyG-BRI (HR:1.13, 95%CI:0.99-1.30) approached statistical significance after full adjustment for mediators. In contrast, in the UK cohort, significant associations persisted for most TyG Index indicators when full adjustment for mediators, including BMI (HR: 1.17, 95% CI: 1.09-1.26), TyG-BMI (HR: 1.16, 95% CI: 1.07-1.26), TyG-WC (HR: 1.13, 95% CI: 1.03-1.25), TyG-FMI (HR: 1.17, 95% CI: 1.07-1.28), and TyG-RBI (HR: 1.15, 95% CI: 1.06-1.24). TyG-BRI also showed the best predictive performance for ischemic stroke in Chinese rural residents (AUC > 0.7) and exhibited an almost linear relationship with ischemic stroke occurrence. Additionally, TyG-BRI presented a U-shaped relationship with the risk of hemorrhagic stroke incidence in the UK (p overall  = 0.041, p non-linear  = 0.017). Multimorbidity mediated the relationship between TyG indices, and ischemic stroke incidence in both cohorts. The mediation percentage for multimorbidity was higher than the sum of individual chronic diseases, with a higher mediation percentage in the Chinese cohort (up to 51%) compared to the UK cohort (up to 27.2%)., Conclusions: Chinese rural residents exhibit higher levels of visceral obesity compared to residents in UK, leading to greater stroke susceptibility mediated by multimorbidity. These findings underscore the importance of comprehensive management of multimorbidity for stroke prevention. The TyG-BRI may serve as a promising predictor of ischemic stroke incidence among rural community residents., Competing Interests: Declarations. Ethics approval and consent to participate: UK Biobank was constructed under ethical approval obtained by the North West Multi-Centre Research Ethics Committee (REC reference: 11/NW/03820) and all participants provided written informed consent prior to participation. ECDRAHC cohort involves human participants and was approved by Harbin Medical University. All authors consent to the publication of this manuscript. Consent for publication: All authors consent to the publication of this manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Gestational diabetes mellitus (GDM) could increase the risks of type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, evidence on its association with cardiometabolic multimorbidity (CMM) was limited. This study aimed to evaluate the association between GDM and the prevalence, incidence, patterns, and progression of CMM; and the role of body mass index (BMI) in such association., Methods: This study included 203,372 women who have given birth in UK Biobank. The diagnoses of GDM and cardiometabolic diseases (including stroke, coronary heart disease [CHD], and T2DM) were reported by participants or obtained through linkage to inpatient hospital data until 31st December 2020. BMI was assessed at the baseline assessment. CMM was defined as having two or more of included cardiometabolic diseases. Logistic regression models and Cox proportional hazard models were used to assess the association between GDM and CMM, and the modifications on both additive and multiplicative scales were assessed to evaluate the effect of BMI on such association., Results: A total of 1217 women had a history of GDM, 2351 participants had CMM at the end of follow-up and 1601 was newly diagnosed during follow-up. GDM was associated with higher prevalence (odds ratio [OR]=4.64, 95 % confidence interval [95 % CI]=3.54-6.08) and incidence (hazard ratio [HR]=3.62, 95 % CI=2.62-5.00) of CMM. In particular, GDM was associated with higher odds of T2DM, coexisting T2DM and vascular disease, and T2DM followed by vascular disease. Formal testing for effect modification suggested multiplicative modification by BMI for the association between GDM and incident CMM., Conclusions: GDM was associated with CMM in women's late life, with multiplicative modification effects of BMI. Our results suggest that maternal and lifestyle interventions (e.g., weight management) are warranted for the primary and secondary prevention of CMM, particularly in women with a history of GDM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Multistate models provide a useful framework for modelling complex event history data in clinical settings and have recently been extended to the joint modelling framework to appropriately handle endogenous longitudinal covariates, such as repeatedly measured biomarkers, which are informative about health status and disease progression. However, the practical application of such joint models faces considerable computational challenges. Motivated by a longitudinal multimorbidity analysis of large-scale UK health records, we introduce novel Bayesian inference approaches for these models that are capable of handling complex multistate processes and large datasets with straightforward implementation. These approaches decompose the original estimation task into smaller inference blocks, leveraging parallel computing and facilitating flexible model specification and comparison. Using extensive simulation studies, we show that the proposed approaches achieve satisfactory estimation accuracy, with notable gains in computational efficiency compared to the standard Bayesian estimation strategy. We illustrate our approaches by analysing the coevolution of routinely measured systolic blood pressure and the progression of three important chronic conditions, using a large dataset from the Clinical Practice Research Datalink Aurum database. Our analysis reveals distinct and previously lesser-known association structures between systolic blood pressure and different disease transitions., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Aim: To assess the prevalence of individual obesity-related complications (ORCs) and multimorbidity (≥ 1, ≥ 2 and ≥ 3 ORCs), and multimorbidity-associated healthcare costs, over 10 years., Methods: This retrospective open cohort study used Discover, a UK database of linked primary and secondary electronic health records. Adults were stratified by body mass index (BMI; overweight: 25-< 30 kg/m 2 ; obesity class I: 30-< 35 kg/m 2 ; obesity class II: 35-< 40 kg/m 2 ; obesity class III: ≥ 40 kg/m 2 ). Outcomes by year since baseline were assessed for serial cross sections across the study period (1 January 2004 to 31 December 2019; the index date was the date of first eligible BMI measurement)., Results: Across 1 410 146 individuals (overweight: 1 008 101; obesity class I: 278 782; obesity class II: 80 621; obesity class III: 42 642), ORC prevalence was higher in successive BMI groups, and increases over time were generally greater for obesity relative to overweight. In those with ORC multimorbidity, both higher BMI and the presence of more ORCs were associated with higher annual per-person healthcare costs. Costs increased over time in those individuals with obesity and one or more ORC, as well as in those with obesity and two or more ORCs., Conclusions: Higher BMI was associated with higher baseline ORC prevalence and a greater increase in ORC prevalence over time, and with higher healthcare costs in those with multimorbidity. To reduce the burden of overweight and obesity on patients and healthcare systems, the presence, number and type of ORCs should be considered in developing effective, targeted prevention and management care pathways., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Achilles tendinopathy is a common condition that is often still symptomatic 10 years after onset. Much of the available research has focussed on active populations, however our experience is patients seeking care in the UK's National Health Service (NHS) may be different., Objectives: To determine the characteristics of patients receiving NHS care for Achilles tendinopathy (AT). To describe the utilisation of resources and the effectiveness of AT management in the NHS., Methods: A data extraction tool was developed and used to retrospectively extract the characteristics of 573 patients diagnosed with Achilles tendinopathy., Results: NHS Achilles tendinopathy patients averaged 57 years old, had a Body Mass Index of 31, and 69% had at least one other long-term health condition. These included musculoskeletal complaints (59%), hypertension (30%), Chronic Obstructive Pulmonary Disease or asthma (17%), cardiovascular disease (13%) and diabetes (13%). Subsequently medication usage was higher than the general population and included drugs that have been linked to the pathogenesis of tendinopathy. On average, healthcare providers conducted 3.8 therapy sessions and 26% of patients had radiological investigations. Outcome measures were commonly absent with Visual Analog Scale (VAS) scores documented in 51% of records, and patient-reported outcome measures like VISA-A only appearing in 3% of cases. Reports on psychosocial factors were seldom documented., Conclusion: Individuals diagnosed with Achilles tendinopathy through NHS services exhibit distinct characteristics that diverge considerably from those currently represented in the published research used to develop clinical guidelines. NHS Achilles tendinopathy patients have multiple long-term health conditions and higher medication usage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: A proinflammatory diet has been associated with a risk of individual chronic diseases, however, evidence on the association between inflammatory dietary patterns and the trajectory of chronic disease multimorbidity is sparse., Objectives: We aimed to investigate the associations of a low-inflammatory diet with the multimorbidity trajectory., Methods: Within the UK Biobank, 102,424 chronic disease-free participants (mean age 54.7 ± 7.9 y, 54.8% female) were followed up to detect multimorbidity trajectory (annual change in the number of 59 chronic diseases). Baseline inflammatory diet index (IDI) and empirical dietary inflammatory pattern (EDIP) were separately calculated from the weighted sum of 32 posteriori-derived (15 anti-inflammatory) and 18 prior-defined (9 anti-inflammatory) food groups, and tertiled as low-, moderate-, and high-inflammatory diet. Data were analyzed using linear mixed effects model, Cox model, and Laplace regression with adjustment for potential confounders., Results: During the follow-up (median 10.23 y), 15,672 and 35,801 participants developed 1 and 2+ chronic conditions, respectively. Adherence to a low-inflammatory diet was associated with decreased multimorbidity risk (hazard ratio [HR IDI ] = 0.84, 95% confidence interval [CI]: 0.81, 0.86; HR EDIP = 0.91, 95% CI: 0.89, 0.94) and a slower multimorbidity accumulation (β IDI = -0.033, 95% CI: -0.036, -0.029; β EDIP = -0.006, 95% CI: -0.010, -0.003) compared with a high-inflammatory diet, especially in participants aged > 60 y (β IDI = -0.051, 95% CI: -0.059, -0.042; β EDIP = -0.020, 95% CI: -0.029, -0.012; both P-interactions < 0.05). The 50th percentile difference (95% CI) of chronic disease-free survival time was prolonged by 0.81 (0.64, 0.97) and 0.49 (0.34, 0.64) y for participants with a low IDI and EDIP, respectively. Higher IDI and EDIP were associated with the development of 4 and 3 multimorbidity clusters (especially for cardiometabolic diseases), respectively., Conclusions: A low-inflammatory diet is associated with a lower risk and slower accumulation of multimorbidity (especially in participants aged > 60 y). A low-inflammatory diet may prolong chronic disease-free survival time., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Cardiometabolic multimorbidity (CMM) and aging are increasing public health concerns. This prospective study used UK Biobank cohort to investigate the relationship between biological aging and the trajectory of CMM to dementia and mortality., Methods: CMM is the coexistence of at least two cardiometabolic diseases (CMD), including stroke, ischemic heart disease, and diabetes. Biological age was calculated using the KDM-BA and PhenoAge algorithms. Accelerated aging indicated biological age advances more rapidly than chronological age., Results: The study included 415,147 individuals with an average age of 56.5 years. During the average 11-year follow-up period, CMD-free individuals with accelerated aging had a significantly greater risk of CMD (KDM-BA, HR 1.456; PhenoAge, HR 1.404), CMM (KDM-BA, HR 1.952; PhenoAge, HR 1.738), dementia (KDM-BA, HR 1.243; PhenoAge, HR 1.212), and mortality (KDM-BA, HR 1.821; PhenoAge, HR 2.047) in fully-adjusted Cox regression models ( p  < 0.05 for all). Accelerated aging had adjusted HRs of 1.489 (KDM-BA) and 1.488 (PhenoAge) for CMM, 1.434 (KDM-BA) and 1.514 (PhenoAge) for dementia, and 1.943 (KDM-BA) and 2.239 (PhenoAge) for mortality in participants with CMD at baseline ( p  < 0.05 for all). CMM significantly mediated accelerated aging's indirect effects on dementia by 13.7% (KDM-BA, HR) and 21.6% (PhenoAge); those on mortality were 4.7% (KDM-BA) and 5.2% (PhenoAge). The population attributable-risk of Life's Essential 8 score (≥80 vs. <80) were 0.79 and 0.43 for KDM-BA and PhenoAge accelerated aging, respectively., Conclusion: Biological aging involves the entire trajectory of CMM from a CMD-free state to CMD, to CMM, and ultimately to dementia and death. Life's Essential 8 may be a potential target to counter age acceleration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Jia, Li, Wan, Lei, Liao, Zhao and Li.)

Background: Chronic kidney disease (CKD) prevalence is steadily increasing, in part due to increased multimorbidity in our aging global population. When progression to kidney failure cannot be avoided, people need unbiased information to inform decisions about whether to start dialysis, if or when indicated, or continue with holistic person-centred care without dialysis (conservative kidney management). Comparisons suggest that while there may be some survival benefit from dialysis over conservative kidney management, in people aged 80 years and over, or with multiple health problems or frailty, this may be at the expense of quality of life, hospitalisations, symptom burden and preferred place of death. Prepare for Kidney Care aims to compare preparation for a renal dialysis pathway with preparation for a conservative kidney management pathway, in relation to quantity and quality of life in multimorbid, frail, older people with advanced CKD., Methods: This is a two-arm, superiority, parallel group, non-blinded, individual-level, multi-centre, pragmatic trial, set in United Kingdom National Health Service (NHS) kidney units. Patients with advanced CKD (estimated glomerular filtration rate < 15 mL/min/1.73 m 2 , not due to acute kidney injury) who are (a) 80 years of age and over regardless of frailty or multimorbidity, or (b) 65-79 years of age if they are frail or multimorbid, are randomised 1:1 to 'prepare for responsive management', a protocolised form of conservative kidney management, or 'prepare for renal dialysis'. An integrated QuinteT Recruitment Intervention is included. The primary outcome is mean total number of quality-adjusted life years during an average follow-up of 3 years. The primary analysis is a modified intention-to-treat including all participants contributing at least one quality of life measurement. Secondary outcomes include survival, patient-reported outcomes, physical functioning, relative/carer reported outcomes and qualitative assessments of treatment arm acceptability. Cost-effectiveness is estimated from (i) NHS and personal social services and (ii) societal perspectives., Discussion: This randomised study is designed to provide high-quality evidence for frail, multimorbid, older patients with advanced CKD choosing between preparing for dialysis or conservative kidney management, and healthcare professionals and policy makers planning the related services., Trial Registration: ISRCTN, ISRCTN17133653 ( https://doi.org/10.1186/ISRCTN17133653 ). Registered 31 May 2017., (© 2024. The Author(s).)

Background: People with severe mental illness who experience co-occurring substance use experience poor outcome including suicide, violence, relapses and use of crisis services. They struggle to access care and treatment due to a lack of an integrated and co-ordinated approach which means that some people can fall between services. Despite these concerns, there is limited evidence as to what works for this population., Objectives: To undertake a realist evaluation of service models in order to identify and refine programme theories of what works under what contexts for this population., Design: Realist synthesis and evaluation using published literature and case study data., Setting: Mental health, substance use and related services that had some form of service provision in six locations in the United Kingdom (five in England and one in Northern Ireland)., Participants: People with lived experience of severe mental illness and co-occurring substance use, carers and staff who work in the specialist roles as well as staff in mental health and substance use services., Results: Eleven initial programme theories were generated by the evidence synthesis and in conjunction with stakeholders. These theories were refined through focus groups and interviews with 58 staff, 25 service users and 12 carers across the 6 case study areas. We identified three forms of service provision (network, consultancy and lead and link worker); however, all offered broadly similar interventions. Evidence was identified to support most of the 11 programme theories. Theories clustered around effective leadership, workforce development and collaborative integrated care pathways. Outcomes that are meaningful for service users and staff were identified, including the importance of engagement., Limitations: The requirement for online data collection (due to the COVID-19 pandemic) worked well for staff data but worked less well for service users and carers. Consequently, this may have reduced the involvement of those without access to information technology equipment., Conclusion: The realist evaluation co-occurring study provides details on how and in what circumstances integrated care can work better for people with co-occurring severe mental health and alcohol/drug conditions. This requires joined-up policy at government level and local integration of services. We have also identified the value of expert clinicians who can support the workforce in sustaining this programme of work. People with co-occurring severe mental health and alcohol/drug conditions have complex and multifaceted needs which require a comprehensive and long-term integrated approach. The shift to integrated health and social care is promising but will require local support (local expert leaders, network opportunities and clarity of roles)., Future Work: Further work should evaluate the effectiveness and cost-effectiveness of service models for this group., Study Registration: This study is registered as PROSPERO CRD42020168667., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128128) and is published in full in Health Technology Assessment ; Vol. 28, No. 67. See the NIHR Funding and Awards website for further award information.

Background: Malnutrition, sarcopenia and frailty are distinct, albeit interrelated, conditions associated with adverse outcomes in adults with cancer, but whether they relate to multimorbidity, which affects up to 90% of people with cancer, is unknown. This study investigated the relationship between multimorbidity with malnutrition, sarcopenia and frailty in adults with cancer from the UK Biobank., Methods: This was a cross-sectional study including 4122 adults with cancer (mean [SD] age 59.8 [7.1] years, 50.7% female). Malnutrition was determined using the Global Leadership Initiative on Malnutrition criteria. Probable sarcopenia and sarcopenia were defined using the European Working Group on Sarcopenia in Older People 2 criteria. (Pre-)frailty was determined using the Fried frailty criteria. Multimorbidity was defined as ≥2 long-term conditions with and without the cancer diagnosis included. Logistic regression models were fitted to estimate the odds ratios (ORs) of malnutrition, sarcopenia and frailty according to the presence of multimorbidity., Results: Genitourinary (28.9%) and breast (26.1%) cancers were the most common cancer diagnoses. The prevalence of malnutrition, (probable-)sarcopenia and (pre-)frailty was 11.1%, 6.9% and 51.2%, respectively. Of the 11.1% of participants with malnutrition, the majority (9%) also had (pre-)frailty, and 1.1% also had (probable-)sarcopenia. Of the 51.2% of participants with (pre-)frailty, 6.8% also had (probable-)sarcopenia. No participants had (probable-)sarcopenia alone, and 1.1% had malnutrition, (probable-)sarcopenia plus (pre-)frailty. In total, 33% and 65% of participants had multimorbidity, including and excluding the cancer diagnosis, respectively. The most common long-term conditions, excluding the cancer diagnosis, were hypertension (32.5%), painful conditions such as osteoarthritis or sciatica (17.6%) and asthma (10.4%). Overall, 80% of malnourished, 74% of (probable-)sarcopenia and 71.5% of (pre-)frail participants had multimorbidity. Participants with multimorbidity, including the cancer diagnosis, had higher odds of malnutrition (OR 1.72 [95% confidence interval, CI, 1.31-2.30; P < 0.0005]) and (pre-)frailty (OR 1.43 [95% CI 1.24-1.68; P < 0.0005]). The odds increased further in people with ≥2 long-term conditions in addition to their cancer diagnosis (malnutrition, OR 2.41 [95% CI 1.85-3.14; P < 0.0005]; (pre-)frailty, OR 2.03 [95% CI 1.73-2.38; P < 0.0005]). There was little evidence of an association of multimorbidity with sarcopenia., Conclusions: In adults with cancer, multimorbidity was associated with increased odds of having malnutrition and (pre-)frailty but not (probable-)sarcopenia. This highlights that multimorbidity should be considered a risk factor for these conditions and evaluated during nutrition and functional screening and assessment to support risk stratification within clinical practice., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Evidence regarding the role of chronic low-grade inflammation in the progression of cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) is currently limited. This prospective cohort study, utilising data from the UK Biobank, included 273,804 adults aged 40-69 years initially free of CMD at baseline. CMM was defined as the coexistence of two or more CMDs, such as coronary artery disease, type 2 diabetes mellitus, hypertension and stroke. The aggregated inflammation score (INFLA-score), incorporating C-reactive protein, white blood cell count, platelet count and granulocyte-to-lymphocyte ratio, quantified chronic low-grade inflammation. Absolute risks (ARs), hazard ratios (HRs) and 95% confidence intervals (CIs) assessed the association of increased INFLA-score with the risk of CMMs and CMDs. The accelerated failure time model explored the effect of INFLA-score on the time to CMM onset, and a restricted cubic spline characterised the dose-dependent relationship between INFLA-score and CMM risk. After a median follow-up of 166.37 months, 13,755 cases of CMM were identified. In quartiles with increasing INFLA-score levels, CMM ARs were 4.41%, 4.49%, 5.04% and 6.01%, respectively; HR increased by 2%, 15% and 36%, respectively, compared to the lowest quartile. The INFLA-score and CMM risk relationship was nonlinear (P for nonlinear < 0.001), exhibiting a significant risk trend change at a score of 9. For INFLA-score < 9, CMM risk increased by 1.9% for each 1-point increase; for INFLA-score ≥ 9, the risk increased by 5.9% for each 1-point increase. Additionally, a higher INFLA-score was associated with an earlier onset of CMM (P < 0.001). Compared to the first INFLA-score quartile, the AFT model revealed adjusted median times to CMM occurrence were 2.92, 6.10 and 13.19 months earlier in the second, third and fourth quartile groups, respectively. Chronic low-grade inflammation is associated with a higher risk of cardiometabolic multimorbidity and earlier onset among middle-aged and older adults. Monitoring and screening the INFLA-score in adults without CMDs may improve early prevention of CMM., (© 2024. The Author(s).)