Cardiovascular risks and bleeding with non-vitamin K antagonist oral anticoagulant versus warfarin in patients with type 2 diabetes : a tapered matching cohort study

Background: We compared the risk of bleeding and cardiovascular disease (CVD) events between non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin in people with type 2 diabetes (T2DM). Methods: 862 Incident NOAC users and 626 incident warfarin users with T2DM were identified from within 40 UK general practice (1/4/2017-30/9/2018). Outcomes included incident hospitalisation for bleeding, CVD and re-hospitalisation for CVD within 12 months since first anticoagulant prescription, identified from linked hospitalisation data. A tapered matching method was applied to form comparison cohorts: coarsened exact matching restricted the comparison to areas of sufficient overlap in missingness and characteristics: (i) demographic characteristics; (ii) clinical measurements; (iii) prior bleeding and CVD history; (iv) prescriptions with bleeding; (v) anti-hypertensive treatment(s); (vi) anti-diabetes treatment(s). Entropy balancing sequentially balanced NOAC and warfarin users on their distribution of (i-vi). Weighted logistic regression modelling estimated outcome odds ratios (ORs), using entropy balancing weights from steps i-vi. Results: The 12-month ORs of bleeding with NOAC (n = 582) vs matched/balanced warfarin (n = 486) were 1.93 (95% confidence interval 0.97-3.84), 2.14 (1.03-4.44), 2.31 (1.10-4.85), 2.42 (1.14-5.14), 2.41 (1.12-5.18), and 2.51 (1.17-5.38) through steps i-vi. ORs for CVD re-hospitalisation was increased with NOAC treatment through steps i-vi: 2.21 (1.04-4.68), 2.13 (1.01-4.52), 2.47 (1.08-5.62), 2.46 (1.02-5.94), 2.51 (1.01-6.20), and 2.66 (1.02-6.94). Conclusions: Incident NOAC use among T2DM is associated with increased risk of bleeding hospitalisation and CVD re-hospitalisation compared with incident warfarin use. For T2DM, caution is required in prescribing NOACs as first anticoagulant treatment. Further large-scale replication studies in external datasets are warranted

Fuzzy Control for Seismic Protection of Semiactive Base-Isolated Structures Subjected to Near-Fault Earthquakes

This paper proposes a new fuzzy logic controller, which is designed for seismic protection of base-isolated structures utilizing piezoelectric friction damper against near-fault earthquakes for different ground sites. According to the elastic design spectrum that Eurocode 8 recommends, one 5% damped elastic design spectrum for Chi-Chi earthquake is proposed to generate artificial earthquakes of different ground sites. The proposed controller employs a hierarchic fuzzy control algorithm, in which a supervisory fuzzy controller governs a sublevel fuzzy controller by altering its input normalization factors according to current level of ground motion. In order to simultaneously reduce the base displacement and superstructure responses of the base-isolated structure during seismic excitations, genetic algorithm is employed to optimize the supervisory fuzzy controller and the preload of piezoelectric friction damper. The efficiency of the proposed controller is also compared with passive controller and a linear quadratic Gauss optimal controller. Numerical results show that the proposed fuzzy logic controller has favorable performance in mitigating the responses of the base-isolated structure

Towards universal health coverage: achievements and challenges of 10 years of healthcare reform in China.

Universal health coverage (UHC) has been identified as a priority for the global health agenda. In 2009, the Chinese government launched a new round of healthcare reform towards UHC, aiming to provide universal coverage of basic healthcare by the end of 2020. We conducted a secondary data analysis and combined it with a literature review, analysing the overview of UHC in China with regard to financial protection, coverage of health services and the reported coverage of the WHO and the World Bank UHC indicators. The results include the following: out-of-pocket expenditures as a percentage of current health expenditures in China have dropped dramatically from 60.13% in 2000 to 35.91% in 2016; the health insurance coverage of the total population jumped from 22.1% in 2003 to 95.1% in 2013; the average life expectancy increased from 72.0 to 76.4, maternal mortality dropped from 59 to 29 per 100 000 live births, the under-5 mortality rate dropped from 36.8 to 9.3 per 1000 live births, and neonatal mortality dropped from 21.4 to 4.7 per 1000 live births between 2000 and 2017; and so on. Our findings show that while China appears to be well on the path to UHC, there are identifiable gaps in service quality and a requirement for ongoing strengthening of financial protections. Some of the key challenges remain to be faced, such as the fragmented and inequitable health delivery system, and the increasing demand for high-quality and value-based service delivery. Given that China has committed to achieving UHC and 'Healthy China 2030', the evidence from this study can be suggestive of furthering on in the UHC journey and taking the policy steps necessary to secure change

Towards universal health coverage: lessons from 10 years of healthcare reform in China.

Universal health coverage (UHC) is driving the global health agenda. Many countries have embarked on national policy reforms towards this goal, including China. In 2009, the Chinese government launched a new round of healthcare reform towards UHC, aiming to provide universal coverage of basic healthcare by the end of 2020. The year of 2019 marks the 10th anniversary of China's most recent healthcare reform. Sharing China's experience is especially timely for other countries pursuing reforms to achieve UHC. This study describes the social, economic and health context in China, and then reviews the overall progress of healthcare reform (1949 to present), with a focus on the most recent (2009) round of healthcare reform. The study comprehensively analyses key reform initiatives and major achievements according to four aspects: health insurance system, drug supply and security system, medical service system and public health service system. Lessons learnt from China may have important implications for other nations, including continued political support, increased health financing and a strong primary healthcare system as basis

Dialysate glucose response phenotypes during peritoneal equilibration test and their association with cardiovascular death : a cohort study

Different measures of rates of transfer of glucose during the peritoneal equilibrium test (PET), undertaken during peritoneal dialysis (PD) might provide additional information regarding a patient's risk of future cardiovascular mortality. This study aimed to characterize the heterogeneity of dialysate glucose (DG) response phenotypes during the PET and compare the cardiovascular mortality rates associated with the different phenotypes. Our cohort was derived from Henan peritoneal dialysis registry. A total of 3477 patients initiating PD in 2007 to 2014 had the DG measured at 0, 2-hour and 4-hour (D0, D2, and D4 respectively) during the PET for estimation of D2/D0 and D4/D0. Deaths mainly due to CVD within 2 years since the initiation of PD were defined as the outcome. Latent class mixed-effect models were fitted to identify distinct phenotypes of the DG response during the PET. Multivariable unconditional Logistic regression models with adjustment for cardiometabolic risk factors were used to compare the 2-year risk of cardiovascular mortality among patients in the different latent classes. Three distinct DG response phenotypes during the PET were identified. Those with consistently high D2/D0 and D4/D0 ratios had a 1.22 [95% confidence interval: 1.02, 1.35] excess risk of a cardiovascular death within 2 years of commencing PD compared with patients with the lowest D2/D0 ratio and decreased D4/D0 ratio after adjustment for cardiometabolic risk factors. Consistently elevated D2/D0 and D4/D0 ratios during the PET are associated with an increased risk of 2-year cardiovascular mortality independent of other cardiometabolic risk factors. In view of the potential bias due to unmeasured confounders (eg, Family history of cardiovascular diseases, and dietary patterns), this association should be further validated in other external cohorts

Differential expression profiling between the relative normal and dystrophic muscle tissues from the same LGMD patient

BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a group of heterogeneous muscular disorders with autosomal dominant and recessive inheritance, in which the pelvic or shoulder girdle musculature is predominantly or primarily involved. Although analysis of the defective proteins has shed some light onto their functions implicated in the etiology of LGMD, our understanding of the molecular mechanisms underlying muscular dystrophy remains incomplete. METHODS: To give insight into the molecular mechanisms of AR-LGMD, we have examined the differentially expressed gene profiling between the relative normal and pathological skeletal muscles from the same AR-LGMD patient with the differential display RT-PCR approach. The research subjects came from a Chinese AR-LGMD family with three affected sisters. RESULTS: In this report, we have identified 31 known genes and 12 unknown ESTs, which were differentially expressed between the relative normal and dystrophic muscle from the same LGMD patient. The expression of many genes encoding structural proteins of skeletal muscle fibers (such as titin, myosin heavy and light chains, and nebulin) were dramatically down-regulated in dystrophic muscles compared to the relative normal muscles. The genes, reticulocalbin 1, kinectin 1, fatty acid desaturase 1, insulin-like growth factor binding protein 5 (IGFBP5), Nedd4 family interacting protein 1 (NDFIP1), SMARCA2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2), encoding the proteins involved in signal transduction and gene expression regulation were up-regulated in the dystrophic muscles. CONCLUSION: The functional analysis of these expression-altered genes in the pathogenesis of LGMD could provide additional information for understanding possible molecular mechanisms of LGMD development

Derivation and external validation of a risk prediction algorithm to estimate future risk of cardiovascular death among patients with type 2 diabetes and incident diabetic nephropathy: prospective cohort study

Objective To derive, and externally validate, a risk score for cardiovascular death among patients with type 2 diabetes and newly diagnosed diabetic nephropathy (DN). Research design and methods Two independent prospective cohorts with type 2 diabetes were used to develop and externally validate the risk score. The derivation cohort comprised 2282 patients with an incident, clinical diagnosis of DN. The validation cohort includes 950 patients with incident, biopsy-proven diagnosis of DN. The outcome was cardiovascular death within 2 years of the diagnosis of DN. Logistic regression was applied to derive the risk score for cardiovascular death from the derivation cohort, which was externally validated in the validation cohort. The score was also estimated by applying the United Kingdom Prospective Diabetes Study (UKPDS) risk score in the external validation cohort. Results The 2-year cardiovascular mortality was 12.05% and 11.79% in the derivation cohort and validation cohort, respectively. Traditional predictors including age, gender, body mass index, blood pressures, glucose, lipid profiles alongside novel laboratory test items covering five test panels (liver function, serum electrolytes, thyroid function, blood coagulation and blood count) were included in the final model. C-statistics was 0.736 (95% CI 0.731 to 0.740) and 0.747 (95% CI 0.737 to 0.756) in the derivation cohort and validation cohort, respectively. The calibration slope was 0.993 (95% CI 0.974 to 1.013) and 1.000 (95% CI 0.981 to 1.020) in the derivation cohort and validation cohort, respectively. The UKPDS risk score substantially underestimated cardiovascular mortality. Conclusions A new risk score based on routine clinical measurements that quantified individual risk of cardiovascular death was developed and externally validated. Compared with the UKPDS risk score, which underestimated the cardiovascular disease risk, the new score is a more specific tool for patients with type 2 diabetes and DN. The score could work as a tool to identify individuals at the highest risk of cardiovascular death among those with DN

Notch1 Pathway Protects against Burn-Induced Myocardial Injury by Repressing Reactive Oxygen Species Production through JAK2/STAT3 Signaling

Oxidative stress plays an important role in burn-induced myocardial injury, but the cellular mechanisms that control reactive oxygen species (ROS) production and scavenging are not fully understood. This study demonstrated that blockade of Notch signaling via knockout of the transcription factor RBP-J or a pharmacological inhibitor aggravated postburn myocardial injury, which manifested as deteriorated serum CK, CK-MB, and LDH levels and increased apoptosis in vitro and in vivo. Interruption of Notch signaling increased intracellular ROS production, and a ROS scavenger reversed the exacerbated myocardial injury after Notch signaling blockade. These results suggest that Notch signaling deficiency aggravated postburn myocardial injury through increased ROS levels. Notch signaling blockade also decreased MnSOD expression in vitro and in vivo. Notably, Notch signaling blockade downregulated p-JAK2 and p-STAT3 expression. Inhibition of JAK2/STAT3 signaling with AG490 markedly decreased MnSOD expression, increased ROS production, and aggravated myocardial injury. AG490 plus GSI exerted no additional effects. These results demonstrate that Notch signaling protects against burn-induced myocardial injury through JAK2/STAT3 signaling, which activates the expression of MnSOD and leads to decreased ROS levels