Validation of a diet-induced Macaca fascicularis model of non-alcoholic steatohepatitis with dietary and pioglitazone interventions.

AIM: To develop an obese, insulin-resistant cynomolgus monkey model of non-alcoholic steatohepatitis (NASH) with fibrosis with a high fat/high cholesterol (HFHC) diet (with or without high fructose) and test its responsiveness to caloric restriction or pioglitazone. METHODS: First, two groups of monkeys (n = 24/group) with histologically proven NASH and fibrosis were fed the HFHC diet for 17 weeks. The treatment group was subjected to a 40% caloric restriction (CR) and had their diet switched from the HFHC diet to a chow diet (DSCR). Paired liver biopsies were taken before and 17 weeks after DSCR. Subsets of monkeys (nine/group) had whole liver fat content assessed by MRI. Next, two groups of monkeys with histologically proven NASH and fibrosis were treated with vehicle (n = 9) or pioglitazone (n = 20) over 24 weeks. RESULTS: The HFHC and DSCR groups lost 0.9% and 11.4% of body weight, respectively. After 17 weeks, non-alcoholic fatty liver disease activity score (NAS) improvement was observed in 66.7% of the DSCR group versus 12.5% of the HFHC group (P < .001). Hepatic fat was reduced to 5.2% in the DSCR group versus 23.0% in the HFHC group (P = .0001). After 24 weeks, NAS improvement was seen in 30% of the pioglitazone group versus 0% of the vehicle group (P = .08). CONCLUSIONS: Both weight loss induced by DSCR and treatment with pioglitazone improve the histological features of NASH in a diet-induced cynomolgus monkey model. This model provides a translational preclinical model for testing novel NASH therapies.

Safety and efficacy of antiplatelet regimens after percutaneous coronary intervention using drug eluting stents: A network meta-analysis of randomized controlled trials.

AIMS: We aimed to determine the efficacy and safety of different anti-platelet regimens after percutaneous coronary intervention (PCI) with drug eluting stent (DES) implantation using a network meta-analysis of randomized controlled trials (RCTs). METHODS: RCTs comparing shorter duration (≤6 months) of dual antiplatelet therapy (S-DAPT) with either aspirin (ASA) or P2Y12 inhibitor monotherapy against longer duration (≥12 months) DAPT (L-DAPT) after PCI were searched in the MEDLINE, EMBASE and COCHRANE databases. End-points of interest were all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stent thrombosis (ST), major bleeding and major or minor bleeding. Network meta-analyses were performed using frequentist approach. RESULTS: Eighteen RCTs with total of 57,942 patients met the inclusion and exclusion criteria. This included 14 RCTs (N = 28,853) of S-DAPT with ASA monotherapy and 4 RCTs (N = 29,089) with P2Y12 inhibitor monotherapy. Compared with L-DAPT, the odds of MI were higher with S-DAPT with ASA monotherapy [OR 1.23; 95% CI 1.01-1.48], but not with P2Y12 inhibitor monotherapy [0.98; 0.85-1.14]. Both S-DAPT regimens lowered rates of major bleeding when compared with L-DAPT; ASA monotherapy [0.70; 0.49-1.00] and P2Y12 monotherapy [0.67; 0.45-0.98]. There were no differences in risks of all-cause or CV death between either regimen of S-DAPT and L-DAPT. However, in the acute coronary syndrome subgroup, ASA monotherapy was associated with increased risk of ST [1.55; 1.021-2.36] but P2Y12 monotherapy was not [0.93; 0.58-1.48]. CONCLUSION: Amongst patients undergoing DES implantation, S-DAPT with P2Y12 inhibitor monotherapy reduces bleeding without increased risk of MI or ST compared with L-DAPT. Prospective trials are needed to evaluate if S-DAPT with P2Y12 monotherapy is superior to S-DAPT with ASA monotherapy for ischemic protection.

Impact of a Stroke Recovery Program Integrating Modified Cardiac Rehabilitation on All-Cause Mortality, Cardiovascular Performance and Functional Performance.

OBJECTIVE: Using a feasibility analysis and matched subgroup analysis, this study investigated the implementation/safety/outcomes of a stroke recovery program (SRP) integrating modified cardiac rehabilitation for stroke survivors. DESIGN: This prospective cohort study of 783 stroke survivors were discharged from an inpatient rehabilitation facility to an outpatient setting; 136 SRP-participants completed a feasibility study and received the SRP including modified cardiac rehabilitation, 473 chose standard of care rehabilitation (nonparticipants), and a group (n = 174) were excluded. The feasibility study assessed the following: safety/mortality/pre-post cardiovascular performance/pre-post function/patient/staff perspective. In addition to the feasibility study, a nonrandomized subgroup analysis compared SRP-participants (n = 76) to matched pairs of nonparticipants (n = 66, with 10 nonparticipants used more than once) for mortality/pre-post function. RESULTS: The feasibility study showed the SRP to have the following (a) excellent safety, (b) markedly low 1-yr poststroke mortality from hospital admission (1.47%) compared with national rate of 31%, (c) improved cardiovascular performance over 36 sessions (103% increase in metabolic equivalent of tasks times minutes), (d) improved function in Activity Measure of Post-Acute Care domains (P < 0.001), (e) positive reviews from SRP-participants/staff. Subgroup analysis showed the SRP to (a) positively impact mortality, nonparticipants had a 9.09 times higher hazard of mortality (P = 0.039), and (b) improve function in Activity Measure of Post-Acute Care domains (P < 0.001). CONCLUSIONS: Stroke survivors receiving a SRP integrating modified cardiac rehabilitation may potentially benefit from reductions in all-cause mortality and improvements in cardiovascular performance and function.

Relation Between Statewide Hospital Performance Reports on Myocardial Infarction and Cardiovascular Outcomes.

Healthcare systems may be judged on quality of care and access to health services. Studies on the association of hospital quality of care scores and clinical outcomes have yielded mixed results. With the help of a richer and more representative database, the aim of our study was to shed light on these inconsistencies. We examined the association of 4 process of care scores (prescription of aspirin, ß blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker used for left ventricular systolic dysfunction, and an overall composite score) for acute myocardial infarction (AMI), reported in the Hospital Performance Reports, with 30-day and 1-year rates of readmission for AMI and cardiovascular (CV) death. Clinical outcomes were from the Myocardial Infarction Data Acquisition System, an administrative database that comprises all patient CV disease admissions to acute care hospitals in New Jersey. CV death was related with overall score (adjusted odds ratio [OR] 0.821, 95% confidence interval [CI] 0.726 to 0.930, p = 0.002) at 30 days and with all 4 scores at 1 year (OR ranging from 0.829 to 0.997, p <0.01). Readmission due to AMI was associated with the overall score (OR 0.789, 95% CI 0.691 to 0.902, p <0.0001) and the aspirin score (OR 0.995, 95% CI 0.990 to 1, p = 0.046) at 30 days. Low hospital performance scores for AMI were associated with increased CV death and readmission for AMI. In conclusion, healthcare providers should allocate their resources to improving hospital performance to decrease AMI case fatality, AMI readmissions, and CV-related healthcare spending.