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Existing methods that use propensity scores for heterogeneous treatment effect estimation on non-experimental data do not readily extend to the case of more than two treatment options. In this work, we develop a new propensity score-based method for heterogeneous treatment effect estimation when there are three or more treatment options, and prove that it generates unbiased estimates. We demonstrate our method on a real patient registry of patients in Singapore with diabetic dyslipidemia. On this dataset, our method generates heterogeneous treatment recommendations for patients among three options: Statins, fibrates, and non-pharmacological treatment to control patients\' lipid ratios (total cholesterol divided by high-density lipoprotein level). In our numerical study, our proposed method generated more stable estimates compared to a benchmark method based on a multi-dimensional propensity score.

This study aims to understand the adverse drug reactions (ADRs) for non-statin antihyperlipidaemic drugs included in the China Anti-hyperlipidemic Drug Database.
An approach of Chinese national database analysis was employed to screen clinical trials involving non-statin antihyperlipidaemic drugs from 1989 to 2019.
The database was provided by the China National Medical Products Administration Information Centre.
In total, 117 clinical studies with 8800 patients were selected from 2650 clinical trials of the Anti-hyperlipidemic Drug Database.
The non-statin antihyperlipidaemic drugs were divided into three groups: (1) fibrates (fenofibrate, gemfibrozil, bezafibrate, etofylline clofibrate); (2) nicotinic acid and derivatives (niacin, acipimox) and (3) others (probucol, cholestyramine).
The results of this study show that first, gastrointestinal symptoms were the most common reactions (6.975%), which account for approximately 50% of the reported cases with ADRs. Second, cholestyramine (16.418%) and gemfibrozil (13.158%) were the most common gastrointestinal side effect-causing non-statin antihyperlipidaemic drugs, which account for one-third of the population. Third, niacin (7.879%) and gemfibrozil (5.000%) were the most likely cause of liver disease symptoms. Finally, niacin (10.909%) and acipimox (18.847%) were the major non-statin antihyperlipidaemic drugs with skin symptoms.
This study revealed that gastrointestinal symptoms were the most common ADRs of fibrates, probucol and cholestyramine in the Chinese population. For nicotinic acid and derivatives, the ADRs of skin symptoms were the most common in China.

Conventional lipid-lowering agents, including statins, ezetimibe, fibrates, bile acid sequestrants, nicotinic acid, bempedoic acid and Omega-3, are essential to the management of dyslipidaemia. However, these agents have been shown to increase the level of plasma proprotein convertase subtilisin/kexin 9 (PCSK9), a serine protease associated with increased cardiovascular risk. This review aims to investigate the impact of commonly available conventional lipid-lowering agents on circulating PCSK9 levels and lipid profiles.
This protocol is conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A systematic search will be conducted in the following databases: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, SCOPUS and ScienceDirect. Additional information will be retrieved from clinical trial registries or from reference list searches. Published and peer-reviewed randomised controlled trials with adults receiving statin, ezetimibe, fibrate, bile acid sequestrant, nicotinic acid, bempedoic acid or Omega-3 monotherapy or in combination for at least 2 weeks, with availability of plasma PCSK9 at the beginning and end of treatment or the net changes in values, will be included. Study selection, data extraction and assessment of the risk of bias will be independently conducted by two investigators. Continuous data will be presented as a standardised mean difference with 95% confidence interval (CI) and dichotomous data as risk ratios with 95% CI. Subgroup analysis and sensitivity analysis will be performed when sufficient studies are included. Publication bias will be assessed with a funnel plot and Egger\'s test.
Ethics approval is not required as this review will only include data from published sources. The results will be published in a peer-reviewed journal.
No patient or members of the general public are involved.
CRD42022297942.

Patients with primary biliary cholangitis (PBC) who respond poorly to ursodeoxycholic acid (UDCA) are increasingly being trialed using fibrates, showing promising results. To further investigate, we performed a meta-analysis to evaluate the benefit of administrating fibrates to patients with PBC. PubMed, EMBASE, and Cochrane library databases were searched using the keywords \"bezafibrate\", \"fenofibrate\", \"fibrate\", \"primary biliary cholangitis\" and clinical studies involving the use of fibrates in patients with PBC were included. The primary outcome of this study was the effect of fibrates administration on biochemical markers related to cholestasis in patients with PBC, and the secondary outcome was the incidence of treatment-related adverse events. A total of 20 studies with 4783 participants were included in this study. The results revealed that adding fibrates could significantly reduce the levels of ALP (fibrates vs. placebo, MD: - 370.14, P = 0.04; fibrates + UDCA vs. UDCA, MD: - 184.15, P < 0.01), total cholesterol (MD: - 2.82, P = 0.04), GGT (fibrates vs. placebo, MD: - 140.88, P < 0.01; fibrates + UDCA vs. UDCA, MD: - 130.73, P = 0.04), alleviate pruritus symptoms (RD: - 0.20, 95% CI: - 0.39 ~  - 0.01, P = 0.04), and did not significantly increase the incidence of treatment-related side effects. Fibrates can significantly improve liver biochemical parameters and alleviate pruritus in PBC patients.

Fibrates, which are agonists of peroxisome proliferator-activated receptor alpha, have received increasing attention in the treatment of primary biliary cholangitis. Reduced alkaline phosphatase levels and improved clinical outcomes were observed in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid (UDCA) monotherapy4 when treated with bezafibrate or fenofibrate combined with UDCA. In contrast to obeticholic acid, which exacerbates pruritus in patients, fibrates have been shown to relieve pruritus. Clinical trial outcomes show potential for the treatment of primary biliary cholangitis by targeting peroxisome proliferator-activated receptors. It is currently agreed that primary biliary cholangitis is an autoimmune-mediated cholestatic liver disease, and peroxisome proliferator-activated receptor is a nuclear receptor that regulates the functions of multiple immune cells, thus playing an important role in regulating innate and adaptive immunity. Therefore, this review focuses on the immune disorder of primary biliary cholangitis and summarizes the regulation of hepatic immunity when peroxisome proliferator-activated receptors are targeted for treating primary biliary cholangitis.

BACKGROUND: This meta-analysis aimed to evaluate the effectiveness of fibrates in the treatment of pruritus in patients with primary biliary cholangitis (PBC), so as to guide the clinical treatment of such cases.
METHODS: Searches of the PubMed, Google Scholar, and Cochrane Library databases were performed to identify randomized controlled trials (RCTs) and prospective studies published up to December 2020 that used bezafibrate and fenofibrate as treatments for pruritus in patients with PBC. Data extraction and quality evaluation of the included literature were performed. Review Manager 5.3 software was employed for statistical analysis of the data.
RESULTS: This meta-analysis included 7 studies, comprising 382 patients with PBC, which assessed the efficacy of bezafibrate and fenofibrate for treating pruritus. The results showed that treatment with fibrates significantly improved pruritus symptoms in patients with PBC [relative risk (RR) =6.52, 95% confidence interval (CI): 3.26-13.06, P<0.00001]. Subgroup analysis revealed that in comparison with fenofibrate (RR =5.34, 95% CI: 0.88-32.62, P=0.07), bezafibrate (RR =25.87, 95% CI: 7.93-84.42, P<0.00001) was more effective in improving pruritic symptoms in patients with PBC. Bezafibrate was also superior to fenofibrate in reducing the degree of pruritus in patients (mean difference =3.36, 95% CI: 2.62-4.09, P=0.05, I2=73%).
CONCLUSIONS: Fibrates can significantly improve pruritus symptoms in patients with PBC but only in a subset of patients. Further studies are needed to elucidate the pathophysiological mechanisms underlying the effect of fibrates on pruritus in PBC, and thus guide future treatment regimens.

To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates.
Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic.
We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty).
The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.

The purpose of the current study is to evaluate the incidence of age-related macular degeneration (AMD) in dyslipidemia-related diseases with or without the use of fibrate. Patients were defined as dyslipidemia-related diseases according to the diagnostic code and lab exam arrangement, then the population was divided into those with fibrate application and those without via 1:2 ratios of propensity-score matching. The primary outcome is the development of AMD after dyslipidemia-related diseases by the Cox proportional hazard regression. Besides, the relationship between the medical compliance of fibrate, presented as medical possession ratio (MPR), and the AMD development was also analyzed. A total of 22,917 patients and 45,834 individuals were enrolled in the study and control groups. There were 572 and 1181 events of any AMD development in the study and control groups which showed identical risk of AMD (aHR: 0.94, 95% CI: 0.85-1.04). However, a reduced risk of any AMD was found in those patients reached a baseline MPR more than 20% (aHR: 0.729, 95% CI: 0.599-0.887, p = 0.0016) and overall MPR more than 5% three years after the diagnosis of dyslipidemia-related diseases (aHR: 0.712, 95% CI: 0.557-0.909, p = 0.0065). Besides, a lower risk of dry-AMD was also found in those patients with the above conditions (aHR: 0.736, 95% CI: 0.599-0.906, p = 0.0038 and aHR: 0.721, 95% CI: 0.557-0.934, p = 0.0133, respectively). In conclusion, the use of fibrate with fair initial medical compliance will decrease the incidence of AMD in patients with dyslipidemia-related diseases, especially for the development of dry-AMD.