Multimorbidity, the presence of two or more conditions in one person, is common but studies are often limited to observational data and single datasets. We address this gap by integrating large-scale primary-care and genetic data from multiple studies to interrogate multimorbidity patterns and producing digital resources to support future research. We defined chronic, common, and heritable conditions in individuals aged ≥65 years, using two large primary-care databases [CPRD (UK) N = 2,425,014 and SIDIAP (Spain) N = 1,053,640], and estimated heritability using the same definitions in UK Biobank (N = 451,197). We used logistic regression to estimate the co-occurrence of pairs of conditions in the primary care data. Linkage disequilibrium score regression was used to estimate genetic similarity between pairs of conditions. Meta-analyses were conducted across databases, and up to three sources of genetic data, for each pair of conditions. We classified pairs of conditions as across or within-domain based on the international classification of disease. We identified 72 chronic conditions, with 43.6% of 2546 pairs showing higher co-occurrence than chance in primary care and evidence of shared genetics. Many across-domain pairs exhibited substantial shared genetics (e.g., iron deficiency anaemia and peripheral arterial disease: genetic correlation R_g = 0.45 [95% Confidence Intervals 0.27:0.64]). 33 pairs displayed negative genetic correlations, such as skin cancer and rheumatoid arthritis (R_g = -0.14 [-0.21:-0.06]), due to potential adverse drug effects. Discordance between genetic and primary care data was also observed, e.g., abdominal aortic aneurysm and bladder cancer co-occurred in primary care but were not genetically correlated (Odds-Ratio = 2.23 [2.09:2.37], R_g = 0.04 [-0.20:0.28]) and schizophrenia and fibromyalgia were less likely to co-occur together in primary care but were positively genetically correlated (OR = 0.84 [0.75:0.94], R_g = 0.20 [0.11:0.29]). Most pairs of chronic conditions show evidence of shared genetics, and co-occurrence in primary care, suggesting shared mechanisms. The identified patterns of shared genetics, negative correlations and discordance between genetic and observational data provide a foundation for future multimorbidity research. UK Medical Research Council [MR/W014548/1].

(1) Introduction: Cardiovascular disease is associated with high mortality, especially in older people. This study aimed to characterize the evolution of combined multimorbidity and polypharmacy patterns in older people with different cardiovascular disease profiles. (2) Material and methods: This longitudinal study drew data from the Information System for Research in Primary Care in people aged 65 to 99 years with profiles of cardiovascular multimorbidity. Combined patterns of multimorbidity and polypharmacy were analysed using fuzzy c-means clustering techniques and hidden Markov models. The prevalence, observed/expected ratio, and exclusivity of chronic diseases and/or groups of these with the corresponding medication were described. (3) Results: The study included 114,516 people, mostly men (59.6%) with a mean age of 78.8 years and a high prevalence of polypharmacy (83.5%). The following patterns were identified: Mental, behavioural, digestive and cerebrovascular; Neuropathy, autoimmune and musculoskeletal; Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological; Non-specific; Multisystemic; Respiratory, cardiovascular, behavioural and genitourinary; Diabetes and ischemic cardiopathy; and Cardiac. The prevalence of overrepresented health problems and drugs remained stable over the years, although by study end, cohort survivors had more polypharmacy and multimorbidity. Most people followed the same pattern over time; the most frequent transitions were from Non-specific to Mental, behavioural, digestive and cerebrovascular and from Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological to Non-specific. (4) Conclusions: Eight combined multimorbidity and polypharmacy patterns, differentiated by sex, remained stable over follow-up. Understanding the behaviour of different diseases and drugs can help design individualised interventions in populations with clinical complexity.

Background: Our objective is to document major healthcare resource use and associated costs in the care of patients with bronchiectasis, with a particular focus on the costs incurred by exacerbations. Methods: We use a unique dataset from the Bronchiectasis Observational Cohort and Biobank UK. The study includes a baseline cohort of 1119 patients with a primary diagnosis of bronchiectasis, followed for up to five years. Data were extracted and linked to centrally held National Health Service (NHS) resource use data. Results: The average age of the cohort was 64 years and 62% were female. The most common bronchiectasis aetiology was idiopathic or post-infectious. Across follow-ups, exacerbations became less frequent: the proportion of patients with no events increased for all settings, while recurrent (≥2) events declined markedly and single-event categories remained largely stable. Exacerbations were predominantly managed in primary care settings. Based on exacerbation frequency and type and applying 2024/2025 NHS reference costs, the estimated total healthcare exacerbation costs for the study population ranged from £2 million to £3.2 million. Disaggregated estimates for the highest cost scenario include: general practitioner (GP)-only exacerbations (n=2824 events; £479 945), emergency department-managed exacerbations (n=311; £260 126) and inpatient-managed exacerbations (n=680; £2 428 291). The average estimated cost per patient over the full period was £1943. This corresponds to a weighted annual average of £495 per patient (including patients with no exacerbations), with most costs attributable to inpatient-managed exacerbations. Specifically, the average cost was £2980 for individuals with one or more exacerbations, £4865 for those with two or more and £5875 for those with three or more. Conclusions: The findings highlight the economic burden of bronchiectasis exacerbations and demonstrate that targeted management strategies to reduce exacerbation rates should increase health benefits and substantially reduce healthcare costs associated with bronchiectasis.