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Background: Studies revealed unidirectional associations between frailty and medication‐related problems (MRPs) among older adults. Less is known about the association between frailty and the risk of MRPs. We aimed to assess the bi‐directional association between frailty and the risk of MRPs in community‐dwelling older adults in five European countries. Methods: Participants were 1785 older adults in the population‐based Urban Health Centres Europe project. Repeated assessments were collected at baseline and one‐year follow‐up, including frailty, the risk of MRPs, and covariates. Linear regression analyses were conducted to examine the unidirectional associations. A cross‐lagged panel modeling was used to assess bi‐directional associations. Results: The unidirectional association between frailty at baseline and the risk of MRPs at follow‐up remained statistically significant after adjusting for covariates (β = 0.10, 95%CI:0.08, 0.13). The association between the risk of MRPs at baseline and frailty at follow‐up shows similar trends. The bi‐directional association was comparable with reported unidirectional associations, with a stronger effect from frailty at baseline to the risk of MRPs at follow‐up than reversed path (Wald test for comparing lagged effects: p < 0.05). Conclusion: This longitudinal study suggests that a cycle may exist where older adults with higher frailty levels are more likely to have a higher risk of MRPs, which in turn contributes to developing a higher level of frailty. Further research is needed to validate our findings and explore underlying pathways. [ABSTRACT FROM AUTHOR]

Objectives Chronic widespread musculoskeletal pain (CWP) is a characteristic symptom of fibromyalgia, which has been shown to be associated with an altered gut microbiome. Microbiome studies to date have not examined the milder CWP phenotype specifically nor have they explored the role of raised BMI. The aim of this study was to investigate whether the microbiome is abnormal in CWP. Methods CWP was assessed using a standardized screening questionnaire in female volunteers from the TwinsUK cohort including 113 CWP cases and 1623 controls. The stool microbiome was characterized using 16S rRNA amplicon sequencing and amplicon sequence variants, and associations with CWP examined using linear mixed-effects models adjusting for BMI, age, diet, family relatedness and technical factors. Results Alpha diversity was significantly lower in CWP cases than controls (Mann–Whitney test, P -values 2.3e-04 and 1.2e-02, for Shannon and Simpson indices respectively). The species Coprococcus comes was significantly depleted in CWP cases (P adj = 3.04e-03). A genome-wide association study (GWAS) performed for C. comes in TwinsUK followed by meta-analysis with three Dutch cohorts (total n  = 3521) resulted in nine suggestive regions, with the most convincing on chromosome 4 near the TRAM1L1 gene (rs76957229, P  = 7.4e-8). A Mendelian randomization study based on the results of the GWAS did not support a causal role for C. comes on the development of CWP. Conclusions We have demonstrated reduced diversity in the microbiome in CWP, indicating an involvement of the gut microbiota in CWP; prospectively the microbiome may offer therapeutic opportunities for this condition. [ABSTRACT FROM AUTHOR]