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Impact of chronic hepatitis on cardiovascular events among type 2 diabetes patients in Taiwan pay-for-performance program – Scientific Reports

Research subjects

Patients with T2DM who joined the P4P from 2008 to 2010 were enrolled. Patients with a confirmed diagnosis of T2DM were defined as those who were hospitalized at least once or came in for outpatient visits at least three times within 1 year and had a primary or secondary diagnosis International Classification of Diseases (ICD) code “250,” “250.00,” or “250.02”38,39. Among them, patients with type 1 DM “250.x1” * or “250.x3;” gestational DM “648.0” or “648.8;” neonatal DM “775.1;” abnormal glucose tolerance test “790.2;” age < 20 years or > 100 years; and those who died within 1 year of joining P4P were excluded. Finally, 283,793 patients were included (Fig. 1). Based on the status of comorbid chronic hepatitis at enrollment, the patients were divided into four groups: no comorbid chronic hepatitis, named as “No chronic hepatitis”; comorbid liver B, named as “Hepatitis B” group; comorbid liver, named as “Hepatitis C” group; patients without viral hepatitis and with comorbid fatty liver were named as the “Fatty liver disease” group and were followed-up until the end of 2017. The “no comorbid chronic hepatitis” group was used as the reference group to analyze the correlation between different types of chronic hepatitis and the risk of cardiovascular disease.

Figure 1
figure 1

Flowchart for study subject selection. DM diabetes mellitus, P4P pay-for-performance, HBV hepatitis B virus, HCV hepatitis C virus.

Ethics statements

The National Health Insurance Research Database (NHIRD) is derived from Taiwan’s mandatory National Health Insurance program was established by the National Health Insurance Administration Ministry of Health and Welfare and maintained by the National Health Research Institute (NHRI). The patient identifications in the National Health Insurance Research Database have been scrambled and de-identified by the Taiwan government, and the database is commonly used for different types of research such as in medical, and public health fields. Thus, informed consent was waived by the Research Ethics Committee of the China Medical University, and the study protocol was approved by the research ethics committee of China Medical University and Hospital (IRB number: CMUH106-REC3-153) and was conducted in accordance with the principles of the Declaration of Helsinki.

Data sources

This retrospective cohort study analyzed data from the National Health Insurance Research Database of the “Applied Health Research Data Integration Service from National Health Insurance Administration”. The data included outpatient prescriptions and treatments, outpatient prescriptions and medical orders, inpatient medical expense lists, inpatient medical expense and medical order lists, insurance details of persons, major injury and illness, medical institution master files, diagnosis, and P4P education records.

Definitions of variables

Hepatitis B: Those with ICD-9 070.2, 070.20, 070.21, 070.22, 070.23, 070.3070.31, 070.32, or 070.33 or ICD-10 B16, B17.0, B18.0, B18.1, or B19.1 as the primary and secondary diagnosis during two outpatient visits or one hospitalization within 365 days of study enrollment.

Hepatitis C: Those with ICD-9 070.41, 070.44, 070.51, or V02.62 or ICD-10 B17.10, B17.11, B18.2, B19.20, B19.21, or Z22.52 as the primary and secondary diagnosis during two outpatient visits or one hospitalization within 365 days of study enrollment.

NAFLD: Those with ICD-9 571.8, 571.9, or ICD-10 K74.4, K74.5, K74.60, K74.69, K76.0, K76.9, etc. as the primary and secondary diagnosis during two outpatient visits or one hospitalization within 365 days of study enrollment, and without the occurrence of a hepatitis B or C code, for whom the first hospital visit within 365 days was defined as the date of diagnosis. Patients with concurrent viral hepatitis and NAFLD were classified as having viral hepatitis.

Age-based categorization included 20–39, 40–54, 55–64, 65–74, and ≥ 75 years age groups. Monthly salary was divided into five grades, namely ≤ NTD 17,280, NTD 17,281–22,800, NTD 22,801–36,300, NTD 36,301–45,800, and ≥ NTD 45,801. Charlson comorbidity index was divided into 0, 1, 2, and ≥ 3 after excluding scores correlated with independent or dependent variables40.

The diabetes complications severity index (DCSI) was scored as 0, 1, and ≥ 2 points. The DCSI was calculated based on the classification and scoring method proposed by Young et al. If the patient had no complication, the score would be 0; for each complication, 1 point would be added; if the complication was serious, 2 points would be added. Based on this calculation method, the maximum score was 13 points41.

Cardiovascular disease: Those with ICD-9 398.91, 402.xx, 404.xx, 410.xx–414.xx, 422.xx, 425.xx or 428.xx, or ICD-10 I09.81, I11, I13, I20–I22, I24, I25, I40–I43, I50, R09.89, etc. as the primary and secondary diagnosis during two outpatient visits or one hospitalization within 365 days of study enrollment42.

Calculation of the coefficient of variation (CV% = standard deviation/mean) of HbA1c and fasting blood glucose: All measurements in the first year were used, and if the measurements were taken less than four times in the first year, measurements taken up to the second year were included. If measurements were taken less than four times in the 2 years, the patient would be excluded.

Adjusted CV = CV/√ (n/n − 1): When the examination data were limited, the examination times would affect the result of the CV. In this case, a relatively correct result of the CV with a reduced effect of the examination times could be obtained by correcting the examination times.

Analytical methods

Descriptive and inferential statistics were carried out according to the research objectives and framework. All research tests were based on a significance level of α = 0.05, and all statistical analyses were conducted using SAS software for Windows, version 9.4 (SAS Institute Inc., Cary, NC, USA). Descriptive statistics such as frequency, percentage, average, and standard deviation were used to describe the dependent and independent variables to be investigated in this study. This study adopted descriptive statistics to present the demographic characteristics, status of comorbidities, blood biochemical indicators, health status, economic factors, and medical care provider characteristics of patients with diabetes. The incidence of cardiovascular disease in patients with T2DM with chronic hepatitis per 1000 person-years was tested using univariate Poisson regression. The relative risks of cardiovascular disease in the four groups were calculated using a Cox proportional hazards model.

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Liver fibrosis linked to CV events, survival in NAFLD, chronic kidney disease

After a median follow-up of 10 years, NAFLD correlated with an increased risk for: “Variable A” – Cardiovascular events; HR = 1.39 “Variable B” – All-cause mortality; HR = 1.1

Source:

Hydes T, et al. Abstract OS048. Presented at: International Liver Congress; June 22-26, 2022; London (hybrid meeting).


Disclosures:
Hydes reports no relevant financial disclosures.


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LONDON — Elevated noninvasive markers of liver fibrosis correlated with an increased risk for cardiovascular events, end-stage renal disease and worse survival in patients with chronic kidney disease and nonalcoholic fatty liver disease.

“Multimorbidity is increasing, and it is vital to understand the clinical consequences of having more than one medical condition,” Theresa Hydes, MBBS, BSc, PhD, NIHR clinical lecturer in hepatology at the University of Liverpool, told Healio. “Fatty liver disease, in particular, is independently associated with several non-liver conditions, including heart disease and chronic kidney disease.”


After a median follow-up of 10 years, NAFLD correlated with an increased risk for: “Variable A” – Cardiovascular events; HR = 1.39 “Variable B” – All-cause mortality; HR = 1.1



Seeking to assess the effect of NAFLD and NAFLD fibrosis on adverse clinical outcomes and mortality among patients with chronic kidney disease (CKD), Hydes and colleagues analyzed data from 26,074 patients using the UK Biobank. Participants provided information related to medical history, demographics and lifestyle factors, which was supplemented via electronic linkage to hospital records and death records.

Researchers used Cox regression to estimate hazard ratios associated with NAFLD and advanced liver fibrosis on CV events, progression to end-stage renal disease (ESRD) and all-cause mortality.

At baseline, 54,5% of patients with CKD had NAFLD, with evidence of advanced fibrosis among 7% [NAFLD fibrosis score (NFS) 0.676], 3.2% [elevated fibrosis-4 (FIB-4) > 2.67] and 1.1% [AST to platelet ratio index (APRI) 1].

After a median follow-up of 10 years, NAFLD correlated with an increased risk for CV events (HR = 1.39; 95% CI, 1.29-1.51) and all-cause mortality (HR = 1.1; 95% CI, 1.01-1.19) but not ESRD (HR = 1.22; 95% CI, 0.95-1.56) in a univariate analysis. Following multivariate adjustment for demographics, metabolic factors and baseline renal functions, NAFLD did not associate with an increased risk for primary outcomes.

Advanced liver fibrosis using all scores correlated with an increased risk for all-cause mortality (HR = 2.34-2.9), and NFS and FIB-4 associated with an elevated risk for CV events (HR = 2.49; 95% CI, 2.11-2.93 and HR = 1.94; 95% CI, 1.53-2.45) and ESRD (HR = 6.85; 95% CI, 4.29-10.94 and HR = 2.35; 95% CI, 1.19-4.67). After full adjustment, FIB-4 correlated with an increased incidence of CV events (HR = 1.39; 95% CI, 1.06-1.82), notably heart failure (HR = 1.65; 95% CI, 1.16-2.33).

Both FIB-4 and APRI associated with all-cause mortality (HR = 1.55; 95% CI, 1.21-2 and HR = 2.83; 95% CI, 1.95-4.11) and NFS ( –1.455) associated with progression to ESRD (HR = 1.89; 95% CI, 1.13-3.17).

“These results highlight the importance of enhanced recognition of fatty liver disease with fibrosis in people with chronic kidney disease to inform the need for vigorous cardiometabolic risk factor control in this group,” Hydes said. “It also suggests the need for work to understand the mechanisms linking these conditions to help drive new drug discoveries.”

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Study identifies an epigenetic regulator that suppresses pathogenic events in rheumatoid arthritis

Study identifies an epigenetic regulator that suppresses pathogenic events in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by chronic inflammation of synovium, eventually leading to joint destruction. Epigenetic alteration (the mechanism of gene expression regulation without DNA sequence changes), such as low levels of DNA methylation, is one of the factors which worsens the RA state. However the mechanism by which the alterations occur remains largely unknown.

In the present study, we identified an epigenetic regulator UHRF1 that was remarkably up-regulated in synovial fibroblasts (SF) from arthritis model mice and RA patients. Previous study showed that UHRF1 is a key player in the maintenance of DNA methylation, although the function for RA is unknown. To understand UHRF1 function for arthritis, we generated mice with SF-specific UHRF1 conditional knockout (cKO) and experimental arthritis was induced.

cKO mice exhibited more severe arthritic phenotypes than the littermate control. Next, to reveal UHRF1 function in SF, RNA-seq and MBD-seq were performed using SF obtained from the control and cKO mice. Integrative genome-wide analyses of the transcriptome and methylome showed that expression of several cytokines was up-regulated in UHRF1-deficient SF accompanied by reduced DNA methylation signatures.

Also, UHRF1 expression in synovium was negatively correlated with several pathogenesis in RA patients. These data suggested that RA pathogenesis is exacerbated when UHRF1 levels are low in SF. Finally, we assessed whether UHRF1 stabilization contributes to improvement of arthritis pathogenesis. Ryuvidine, which was identified as a candidate chemical compound to the stabilize UHRF1 protein, was administrated in arthritis model mice.

The results showed that arthritis pathogenesis was ameliorated by treatment with Ryuvidine. Also, the development of organoids derived from RA-SF was suppressed by Ryuvidine.

This study demonstrated that UHRF1 expressed in SF with RA has a protective role in suppressing multiple pathogenic events in arthritis, suggesting that targeting UHRF1 could be a therapeutic strategy for RA.

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Clopidogrel monotherapy linked with reduced risk of net adverse clinical events, study finds

Clopidogrel monotherapy linked with reduced risk of net adverse clinical events, study finds

Results from a real-world study investigating safety and effectiveness of clopidogrel versus aspirin monotherapy beyond 12 months after PCI in high-risk patients during the chronic maintenance period. This study found that clopidogrel monotherapy was associated with reduced risk of net adverse clinical events (NACE; all-cause death, MI, stent thrombosis, stroke, or BARC type 2, 3, or 5 bleeding) and MACCE (death, MI, stent thrombosis, stroke), and a numerical decrease in major or clinically relevant nonmajor bleeding (BARC type 2, 3, or 5 bleeding), compared with aspirin monotherapy. The findings were presented today as late-breaking clinical research at the Society for Cardiovascular Angiography & Interventions (SCAI) 2022 Scientific Sessions.

P2Y12 inhibitor monotherapy reduces bleeding risk without increasing the risk of ischemic events compared with dual antiplatelet therapy (DAPT), especially in the first 12 months following percutaneous coronary intervention (PCI). Recent research showed that among patients who were event free for six to 18 months post-PCI and successfully received the intended duration of DAPT, clopidogrel monotherapy was superior compared with aspirin monotherapy in terms of NACE. However, optimal antiplatelet monotherapy during the chronic maintenance period beyond 12 months after PCI with drug-eluting stents in high-risk patients in real-world settings is previously unknown.

In total, 8,377 consecutive patients at high risk for both bleeding and thrombosis were identified from the prospective Fuwai PCI Registry if they satisfied one clinical and one angiographic criterion. Patients who received antiplatelet (aspirin or clopidogrel) monotherapy longer than 12 months and were free from ischemic and bleeding events at 12-month post-PCI without extended duration of DAPT were included. The primary endpoint was net adverse clinical events (NACE) from 12 to 30 months. The key secondary endpoints were major adverse cardiac or cerebral events (MACCE) and major or clinically relevant nonmajor bleeding (BARC type 2, 3 or 5).

“These findings show for the first time clopidogrel monotherapy is associated with reduced risk of long-term NACE and MACCE,” said Hao-Yu Wang, Cardiometabolic Medicine Center, Coronary Heart Disease Center, Department of Cardiology, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. “Our results may have important practical implications for determining the optimal treatment for patients requiring a single antiplatelet drug, either aspirin or clopidogrel, for secondary prevention of ischemic events in high-risk PCI population.”

Of 7,392 high-risk patients that were event-free after the first year and adherent to DAPT, 5,664 patients who received antiplatelet monotherapy (clopidogrel monotherapy: n=1,974 and aspirin monotherapy: n=3690) were included in the present analysis. Researchers found that between 12 and 30 months, the net adverse clinical events were lower with clopidogrel monotherapy compared to aspirin monotherapy (Kaplan-Meier estimate: 2.5% vs. 5.0%; adjusted HR:0.566, 95% CI: 0.403-0.795). Clopidogrel monotherapy was associated with lower risk for MACCE (Kaplan-Meier estimate: 1.0% vs. 3.1%, log-rank p = 0.001 ), as well as lower incidence rates of all-cause death, MI, and stroke. The difference in risk between the groups was statistically similar for major or clinically relevant nonmajor bleeding (Kaplan-Meier estimate: 1.5% vs. 2.1%, log-rank p = 0.199).

Researchers recommended that their findings should be further investigated through a randomized clinical trial.

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Chronic Pain and Mental Health

Chronic Pain and Mental Health

Chronic Pain and Mental Health

April 27, 2022 at 1:30 PM to 2:30 PM

This session will be presented by Associate Professor Michael Hildebrand, from the Department of Neuroscience.

Chronic pain represents a highly prevalent and debilitating healthcare crisis, with direct connections to mental health challenges. The ongoing opioid epidemic illustrates the urgent need to develop new therapeutic approaches for pain that are both safe and effective. In this session, Dr. Mike Hildebrand will define what pain is, with a discussion on what factors shape our experiences of pain and how changes in neurobiological mechanisms of pain processing can lead to chronic pain. This includes highlighting the discrepancies in sex and species between pain patients and typical preclinical pain models, and Dr. Hildebrand’s work aimed at addressing some of these translational divides.

Mental Health Speaker Series

This session is part of the Healthy Workplace Mental Health Speaker Series 2021/2022. Find out more.

Registration

To register for this virtual event, please fill out the form here. You will receive a Zoom link closer to the session date.