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Objectives Hand synovitis, a potentially modifiable pathological lesion, is common and associated with pain and hand OA; nevertheless, its pathogenesis remains uncertain. This study investigated the relationship between gut microbiota dysbiosis and hand synovitis prevalence and evaluated whether bile acids mediate the association. Methods Participants were derived from a community-based observational study. Synovitis in each hand joint was assessed using US. Gut microbiota was evaluated using 16S ribosomal RNA amplicon sequencing on faeces, and plasma bile acids were measured by HPLC mass spectrometry. We examined the relationship between gut microbiota dysbiosis and hand synovitis prevalence, as well as the extent to which bile acids were involved in the association. Results Among 1336 participants (mean age: 63.2 years; women: 58.8%), 18.3% had prevalent hand synovitis (unilateral in 13.6% and bilateral in 4.7%). β-diversity, but not α-diversity, of gut microbiota was significantly associated with prevalent hand synovitis. Higher relative abundance of the genus Prevotella and lower relative abundance of the genus Blautia were significantly associated with the prevalence of hand synovitis. Similar associations were also observed for laterality and the number of joints affected by hand synovitis. The association between Prevotella and hand synovitis was partially mediated through its effect on tauroursodeoxycholic acid and glycoursodeoxycholic acid, the mediation proportions being 25.7% and 21.6%, respectively. Conclusion Our findings suggest that gut microbiota dysbiosis is associated with the prevalence of hand synovitis. Such an association appears to be partially mediated by plasma bile acids. [ABSTRACT FROM AUTHOR]

Objectives Angiotensin II is implicated in GCA pathology. We examined whether the use of angiotensin receptor blockers (ARBs) is associated with GCA risk compared with angiotensin-converting enzyme inhibitors (ACEis) or other antihypertensives. Methods We performed a matched cohort study including adults who were initiators of antihypertensives in UK primary care data between 1995 and 2019. Treatment-naïve individuals without prior GCA or PMR were categorized into three groups—ARB initiators, ACEi initiators, or other antihypertensive initiators (beta-blockers, calcium channel blockers, diuretics or alpha-adrenoceptor blockers)—and followed for up to 5 years. Incident GCA was defined using validated Read codes, with age of onset ≥50 years and two or more glucocorticoid prescriptions. Inverse probability–weighted Cox models were used to model outcome risk, adjusting for lifestyle parameters, comorbidities and comedications. Results Among >1 million new starters of antihypertensives (81 780 ARBs, 422 940 ACEis and 873 066 other antihypertensives), the incidence rate of GCA per 10 000 patient-years was 2.73 (95% CI 2.12, 3.50) in the ARB group, 1.76 (95% CI 1.25, 2.39) in the ACEi group and 1.90 (95% CI 1.37, 2.56) in the other antihypertensives group. The hazard of GCA was higher in ARB initiators [hazard ratio (HR) 1.55; 95% CI 1.16, 2.06] than initiators of ACEis, but similar between initiators of other antihypertensives and ACEis (HR 1.08; 95% CI 0.87, 1.35). Conclusions Initiation of ARBs is associated with a higher risk of GCA compared with ACEis or other antihypertensives. Mechanistic studies of angiotensin receptor biology will provide further clarity for our findings. [ABSTRACT FROM AUTHOR]

Objectives To examine trends in the initial prescription of commonly-prescribed analgesics and patient- as well as practice-level factors related to their selection in incident OA. Methods Patients consulting with incident clinical OA between 2000–2016 were identified within The Health Improvement Network in the United Kingdom (UK) general practice. Excluded were patients who had history of cancer or were prescribed the analgesics of interest within 6 months before diagnosis of OA. Initial analgesic prescription included oral non-selective NSAID, oral selective cyclooxygenase-2 inhibitor, topical NSAID, paracetamol, topical salicylate or oral/transdermal opioid within 1 month after OA diagnosis. Results ∼44% of patients with incident OA (n  = 125 696) were prescribed one of these analgesics. Incidence of oral NSAID prescriptions decreased whereas other analgesic prescriptions, including oral opioid prescriptions, increased (all P -for-trend < 0.001). Patients with a history of gastrointestinal disease were more likely to receive topical NSAIDs, paracetamol or oral/transdermal opioids. Only 38% of patients with history of gastrointestinal disease and 21% of patients without it had co-prescription of gastroprotective agent with oral NSAIDs. Oral/transdermal opioid prescription was higher among the elderly (≥65 years), women, obesity, current smoker, and patients with gastrointestinal, cardiovascular or chronic kidney disease. Prescription of oral opioids increased with social deprivation (P -for-trend < 0.05) and was highest in Scotland, whereas transdermal opioid prescription was highest in Northern Ireland (all P -for-homogeneity-test < 0.05). Conclusion The initial prescription pattern of analgesics for OA has changed over time in the UK. Co-prescription of gastroprotective agents with oral NSAIDs remains suboptimal, even among those with prior gastrointestinal disease. [ABSTRACT FROM AUTHOR]