Glucagon-like Peptide-1 Receptor Agonist Use in Patients With Liver Cirrhosis and Type 2 Diabetes.

BACKGROUND AND AIMS: Liver cirrhosis is often associated with type 2 diabetes (T2D), but research on treatment of T2D in cirrhotic patients is scarce. We investigated the long-term outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D and cirrhosis. METHODS: Using propensity score matching, we selected 467 matched pairs of GLP-1 RA users and nonusers from the National Health Insurance Research Database of Taiwan from January 1, 2008, to December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to compare the outcomes between GLP-1 RA users and nonusers. RESULTS: The mean follow-up time was 3.28 and 3.06 years for GLP-1 RA users and nonusers, respectively. The rates of death were 27.46 and 55.90 per 1000 person-years for GLP-1 RA users and nonusers, respectively. The multivariable-adjusted models showed that GLP-1 RA users had lower risks of mortality (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [CI], 0.32-0.69), cardiovascular events (aHR, 0.6; 95% CI, 0.41-0.87), decompensated cirrhosis (aHR, 0.7; 95% CI, 0.49-0.99), hepatic encephalopathy (aHR, 0.59; 95% CI, 0.36-0.97), and liver failure (aHR, 0.54; 95% CI, 0.34-0.85) than nonusers. A longer cumulative duration of GLP-1 RA use had a lower risk of these outcomes than GLP-1 RA nonuse. CONCLUSIONS: This population-based cohort study showed that GLP-1 RA users exhibited a significantly lower risk of death, cardiovascular events, decompensated cirrhosis, hepatic encephalopathy, and liver failure in patients with T2D and compensated liver cirrhosis. Additional studies are needed to confirm our results.

Association between multimorbidity patterns and incident depression among older adults in Taiwan: the role of social participation.

BACKGROUND: Previous research has found different multimorbidity patterns that negatively affects health outcomes of older adults. However, there is scarce evidence, especially on the role of social participation in the association between multimorbidity patterns and depression. Our study aimed to explore the relationship between multimorbidity patterns and depression among older adults in Taiwan, including the social participation effect on the different multimorbidity patterns. METHODS: Data were retracted from the Taiwan longitudinal study on ageing (TLSA) for this population-based cohort study. 1,975 older adults (age > 50) were included and were followed up from 1996 to 2011. We used latent class analysis to determine participants' multimorbidity patterns in 1996, whereas their incident depression was determined in 2011 by CES-D. Multivariable logistic regression was used to analyse the relationship between multimorbidity patterns and depression. RESULTS: The participants' average age was 62.1 years in 1996. Four multimorbidity patterns were discovered through latent class analysis, as follows: (1) Cardiometabolic group (n = 93), (2) Arthritis-cataract group (n = 105), (3) Multimorbidity group (n = 128) and (4) Relatively healthy group (n = 1649). Greater risk of incident depression was found among participants in the Multimorbidity group (OR: 1.62; 95% CI: 1.02-2.58) than the Relatively healthy group after the multivariable analysis. Compare to participants in the relatively healthy group with social participation, participants in the arthritis-cataract group without social participation (OR: 2.22, 95% CI: 1.03-4.78) and the multimorbidity group without social participation (OR: 2.21, 95% CI: 1.14-4.30) had significantly increased risk of having depression. CONCLUSION: Distinct multimorbidity patterns among older adults in Taiwan are linked with the incident depression during later life, and social participation functioned as a protective factor.

Human papillomavirus symptomatic infection associated with increased risk of new-onset alopecia areata: A nationwide population-based cohort study.

BACKGROUND: We investigated the correlation between a history of human papillomavirus (HPV) infection and alopecia areata risk. METHODS: The study cohort comprised 30,001 patients with newly diagnosed HPV infection between 2000 and 2012; and with use of computer-generated randomly numbers, patients not had HPV infection were randomly selected as the comparison cohort. HPV infection cohort were matched to comparison individuals at a 1:1 ratio by age, gender and index year. All study individuals were followed up until they developed alopecia areata, withdraw from the insurance program, lost to follow-up, or until the end of 2013. Cox proportional hazards regression analysis was used to analyze the risk of alopecia areata with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted hazard ratio (aHR) of alopecia areata for HPV patients relative to controls was 2.55 (95% C.I. = 1.88-3.47) after adjusting sex, age and comorbidities. Subgroup analysis indicated that patients with HPV infections had a significantly greater risk of alopecia areata for both genders, all age subgroups, and those with mental disorder diseases. CONCLUSIONS: A history of HPV infection is associated with the development of subsequent alopecia areata in Taiwanese subjects.

Association of urate-lowering drugs with the risk of future urolithiasis in patients with gout: A population-based nested case-control study.

BACKGROUND: Patients with gout have an increased risk of urolithiasis and usually need urate-lowering therapy (ULT) for the prevention of disease progression. However, there is a paucity of clinical data regarding the risk of future urolithiasis in ULT users. METHODS: This nested case-control study was performed using the Taiwan National Health Insurance Research Database. The aim of this study was to examine whether ULT (xanthine oxidase inhibitors [XOIs] or uricosuric agents) is associated with risk of future urolithiasis in patients with gout. Data were collected from January 2000 to December 2012. RESULTS: This study included 2307 case patients and 2307 matched controls. Case patients had gout that developed into urolithiasis, and control patients had gout but were not diagnosed with urolithiasis during the study period. Patients had a mean age of 56.3 years at diagnosis of gout, and 83.2% were male patients. No association was detected between use of XOIs or uricosuric agents and risk of future urolithiasis. Furthermore, there was no significant difference in the risk of future urolithiasis in patients exposed to various cumulative days of XOI or uricosuric prescriptions. CONCLUSION: The present study provides evidence that neither XOIs nor uricosuric agents are associated with risk of future urolithiasis in patients with gout. Before the availability of more clinical evidence, ensuring high fluid intake and prospective monitoring of urolithiasis development are still important for uricosuric agent users.

Risk of non-typhoidal Salmonella infection in patients with cholecystectomy: Results from a nationwide matched cohort study in Taiwan.

BACKGROUND: The current study was designed to investigate the association between cholecystectomy and the risk of non-typhoidal Salmonella (NTS) infection. METHODS: We obtained claims-based data from the Taiwan National Health Insurance Research Database (NHIRD) to perform a nationwide cohort study. A propensity score (PS)-matching analysis was performed with a ratio of 1:2 in the cholecystectomy cohort and cholecystectomy-free group to reduce selection bias. Both groups were followed until NTS diagnosis, a dropout from the insurance programme or the end of 2013. Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of NTS infection between the cholecystectomy and cholecystectomy-free groups. RESULTS: Our study enrolled 197 444 patients who had undergone cholecystectomy and 394 888 patients who did not receive cholecystectomy. The adjusted HR (aHR) of NTS infection was 1.34 (95% CI, 1.13-1.58; P < .001) for the cholecystectomy group after adjusting for demographical characteristics and relevant comorbidities. The study population is predominantly female patients (55%) and older (58% older than 50 years). The subgroup analysis revealed that both sexes and notably, patients aged >50, who underwent cholecystectomy had a higher risk of NTS infection than the matched controls. Follow-up of patients who underwent cholecystectomy showed that they had a significantly higher risk of NTS infection for more than 6 months after the procedure. CONCLUSIONS: Our study showed that cholecystectomy might be an independent risk factor for subsequent NTS infection.

Risk of Total Knee and Hip Arthroplasty in Patients With Rheumatoid Arthritis: A 12-Year Retrospective Cohort Study of 65,898 Patients.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that causes the destruction of soft tissues and cartilage around joints. Owing to the widespread use of potent disease-modifying antirheumatic drugs, the need for total knee and hip arthroplasties (TKA and THA) has been reduced in patients with RA. However, the current association between RA and either THA or TKA has not been demonstrated in large-scale epidemiological studies. METHODS: We conducted a large-scale retrospective cohort study of patients diagnosed with RA during a 12-year period (2000-2012) in Taiwan. We recruited 32,949 patients with RA and 32,949 individually propensity score-matched non-RA controls. RESULTS: After adjusting for confounding factors, we found that the risk of THA or TKA was 4.02 times higher in patients with RA than in those without RA (95% confidence interval [CI], 3.77-4.52). The risk of THA or TKA was highest in patients with RA younger than 40 years (adjusted hazard ratio, 43.18; 95% CI, 16.01-116.47). Compared with non-RA patients, patients with RA were 4.82 times more likely to undergo THA (95% CI, 3.84-6.04), 3.85 times more likely to undergo TKA (95% CI, 3.48-4.25), and 19.06 times more likely to undergo both THA and TKA (95% CI, 8.90-40.80). CONCLUSION: These findings document a 4.02-fold greater long-term risk of undergoing THA or TKA in RA patients relative to non-RA patients in Taiwan.

Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial.

BACKGROUND: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. METHODS: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. FINDINGS: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. INTERPRETATION: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. FUNDING: Eli Lilly and Company.

Risk of dyslipidemia and major adverse cardiac events with tofacitinib versus adalimumab in rheumatoid arthritis: a real-world cohort study from 7580 patients.

Objective: To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA). Methods: Data of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality. Results: A total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076-1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760-1.303]) and all-cause mortality (HR, 1.402 [0.887-2.215]). Conclusion: Tofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality.

Corrigendum to "Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated population: a retrospective cohort study from the TriNetX US collaborative networks".

[This corrects the article DOI: 10.1016/j.eclinm.2022.101619.].

Recent targets of osteoarthritis research.

Osteoarthritis is one of the most common diseases and poses a significant medical burden worldwide. Currently, the diagnosis and treatment of osteoarthritis primarily rely on clinical symptoms and changes observed in radiographs or other image modalities. However, identification based on reliable biomarkers would greatly improve early diagnosis, help with precise monitoring of disease progression, and provide aid for accurate treatment. In recent years, several biomarkers for osteoarthritis have been identified, including image modalities and biochemical biomarkers such as collagen degradation products, pro- or anti-inflammatory cytokines, micro RNAs, long non-coding RNAs, and circular RNAs. These biomarkers offer new insights in the pathogenesis of osteoarthritis and provide potential targets for further research. This article reviews the evolution of osteoarthritis biomarkers from the perspective of pathogenesis and emphasizes the importance of continued research to improve the diagnosis, treatment, and management of osteoarthritis.