Renin-angiotensin system (RAS) inhibitors have been suggested as protective agents in Parkinson's disease (PD). However, epidemiological evidence on the association between RAS inhibitors and the ...development of PD is inconsistent.
To investigate the effect of RAS inhibitors on PD risk in patients with ischemic heart disease (IHD) by type and cumulative duration of RAS inhibitors and their degree of blood-brain barrier (BBB) penetration ability.
This was a propensity score-matched retrospective cohort study using 2008-2019 healthcare claims data from the Korean Health Insurance Review and Assessment database. The association between RAS inhibitor use and PD in patients with IHD was evaluated using multivariate Cox proportional hazard regression analysis. The risks are presented as adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).
Over a 10-year follow-up, 1,086 of 62,228 IHD patients developed PD. The Cox regression model showed that the use of RAS inhibitors was significantly associated with a lower risk of PD (aHR = 0.75; 95% CI 0.66-0.85) than the non-use of RAS inhibitors. Specifically, this reduced risk of PD only remained with the use of BBB-crossing angiotensin II receptor blockers (ARBs) (aHR = 0.62; 95% CI = 0.53-0.74), and this association was more definite with an increasing cumulative duration. A significantly reduced risk of PD was not observed with the use of BBB-crossing angiotensin-converting enzyme inhibitors.
The use of ARBs with BBB-penetrating properties and a high cumulative duration significantly reduces the risk of PD in IHD patients. This protective effect could provide insight into disease-modifying drug candidates for PD.
Recent studies on renin-angiotensin system (RAS) inhibitors have reported a reduced risk of Alzheimer's disease (AD). Nevertheless, the effect of RAS inhibitor type and blood-brain barrier (BBB) ...permeability on the risk of AD is still unknown.
To assess the effects of RAS inhibitors on the risk of AD based on the type and BBB permeability and investigate the cumulative duration-response relationship.
This was a population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database records from 2008 to 2019. The data of patients diagnosed with ischemic heart disease between January 2009 and June 2009 were identified for inclusion in the analyses. Propensity score matching was used to balance RAS inhibitor users with non-users. The association between the use of RAS inhibitors and incident AD was evaluated using a multivariate Cox proportional hazard regression model. The results are presented in adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).
Among the 57,420 matched individuals, 7,303 developed AD within the follow-up period. While the use of angiotensin-converting enzyme inhibitors (ACEIs) was not significantly associated with AD risk, the use of angiotensin II receptor blockers (ARBs) showed a significant association with reduced risk of incident AD (aHR = 0.94; 95% CI = 0.90-0.99). Furthermore, the use of BBB-crossing ARBs was associated with a lower risk of AD (aHR = 0.83; 95% CI = 0.78-0.88) with a cumulative duration-response relationship. A higher cumulative dose or duration of BBB-crossing ARBs was associated with a gradual decrease in AD risk (
). No significant association between the use of ACEIs and the risk of AD was observed regardless of BBB permeability.
Long-term use of BBB-crossing ARBs significantly reduced the risk of AD development. The finding may provide valuable insight into disease-modifying drug options for preventing AD in patients with cardiovascular diseases.
Background:
The use of opioid–gabapentinoid combinations has increased, raising several safety concerns. However, meta-analysis studies focusing on this issue are limited.
Objective:
To evaluate the ...risk of central nervous system (CNS) depression, gastrointestinal (GI) adverse events, and mortality of combination therapy compared with those of opioid therapy and to explore the differences in the results according to study design and indications.
Methods:
Relevant studies were selected (published before 30 January 2022) by searching the MEDLINE, Embase, and CENTRAL databases. The pooled odds ratios (OR) with 95% confidence intervals (CI) of the outcomes were estimated using the Mantel–Haenszel method. Subgroup and meta-regression analyses were performed according to study characteristics. Quality assessment was conducted using the Risk of Bias 2 tool for randomized controlled trials (RCTs) and Cochrane Collaboration’s Risk of Bias in non-RCTs tool for non-randomized trials.
Results:
Adverse events were reported in 26 RCTs and 7 non-RCTs, and mortality was reported in 10 non-RCTs. Compared to opioid therapy, dizziness, cognitive dysfunction, and respiratory depression in combination therapy significantly increased in non-RCTs (OR 3.26, 95% CI 1.82–5.85; OR 3.13, 95% CI 1.51–6.50; OR 1.71, 95% CI 1.31–2.24, respectively), and a similar trend for dizziness and cognitive dysfunction was also identified in the RCT analysis, although the difference was not significant. Combination therapy for cancer pain was associated with the highest risk of sedation in subgroup analysis. Combination therapy significantly decreased the risk of GI adverse events, including nausea, vomiting, and constipation. The mortality risk associated with combination therapy was higher than that associated with opioid therapy (OR 2.76, 95% CI 1.26–6.05).
Conclusion:
Opioid-gabapentinoid combination therapy could be associated with an increased risk of CNS depression and mortality, despite tolerable GI adverse events. These data suggest that combination therapy requires close monitoring of CNS depression, especially in cancer patients. Caution is needed in interpreting the clinical meanings owing to the lack of risk difference in respiratory depression in the RCT-only analysis and the absence of RCT or prospective studies investigating mortality.
The Compact Muon Solenoid is a large a complex general purpose experiment at the CERN Large Hadron Collider (LHC), built and maintained by many collaborators from around the world. Efficient ...operation of the detector requires widespread and timely access to a broad range of monitoring and status information. To that end the Web Based Monitoring (WBM) system was developed to present data to users located anywhere from many underlying heterogeneous sources, from real time messaging systems to relational databases. This system provides the power to combine and correlate data in both graphical and tabular formats of interest to the experimenters, including data such as beam conditions, luminosity, trigger rates, detector conditions, and many others, allowing for flexibility on the user's side. This paper describes the WBM system architecture and describes how the system has been used from the beginning of data taking until now (Run1 and Run 2).
This paper describes an intra-panel interface which can be applied to a large panel with high resolution and high definition. For good signal integrity and low electro-magnetic interference level, ...four level signaling is used. And to reduce PCB size, point to point signaling is used. The interface supports WUXGA, 12 bit color depth panel which has larger than 30 inch size. It is designed with a 0.18 um CMOS process. And measurements show it works properly in 25 cm long PCB, which is the same condition of 30 inch panel size.
— As thin‐film‐transistor liquid‐crystal‐display (TFT‐LCD) panels become larger and provide higher resolution, the propagation delay of the row and column lines, the voltage modulation of Vcom, and ...the response time of the liquid crystal affect the display images now more than in the past. It is more important to understand the electrical characteristics of TFT‐LCD panels these days. There are several commercial products that simulate the electrical and optical performance of TFT‐LCDs. Most of the simulators are made for panel designers. However, this research is for circuit, system, and panel designers. It is made in a SPICE and Cadence environment as a commercial circuit‐design tool. For circuit and system designers, it will help to design the circuit around a new driving method. Also, it can be easily modified for every situation. It also gives panel designers design concepts. This paper describes the electrical model of a 15‐in. XGA (1024 × 768) TFT‐LCD panel. The parasitic resistance and capacitance of the panel are obtained by 3‐D simulation of a subpixel. The accuracy of these data is verified by the measured values of an actual panel. The developed panel simulation platform, the equivalent circuit of a 1 5‐in. XGA panel, is simulated by HSPICE. The results of simulation are compared with those of experiment, according to changing the width of the OE signal. The proposed simulation platform for modeling TFT‐LCD panels can be especially applied to large‐sized LCD TVs. It can help panel and circuit designers to verify their ideas without making actual panels and circuits.
This paper presents a register controlled delay lock loop (RCDLL) with a time-to-digital converter (TDC) and a new fine delay line (FDL) scheme. The architecture of the proposed DLL uses a ...time-to-digital converter (TDC), a digital-to-time converter (DTC) scheme for short length of coarse delay line (CDL), and a open loop duty cycle corrector (DCC). While the conventional DLL has two feedback loops, the DLL with an open loop DCC has only one loop. So, it occupies a small area compared to the conventional one. Moreover, new FDL scheme is proposed which is capable of seamless boundary switching with a fixed delay step. HSPICE simulation results are based with ANAM 0.18mum 1P6M CMOS process with 1.5V power supply voltage. Upon the simulation results, the proposed DLL operates correctly from 200MHz to 800MHz. The power consumption is less than 24mW at 800MHz. The active area of the design is 0.178mm 2
This paper describes an all digital locked-loop (DLL) with a mixed structure of measure-controlled DLL (MCDLL) and register-controlled DLL (RCDLL). The DLL utilized time to digital converter (TDC) ...and digital to time converter (DTC) using ring counter for wide range operation with small area, fast lock and duty cycle correction (DCC). Simulation results show lock time less than 40 cycles, 1% duty correction error from 50plusmn10% duty external clock, 12mW power dissipation at 800MHz with a 1.5V supply voltage and a wide locking range from 100MHz to 800MHz in a 0.18mum CMOS technology
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