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Aim Sodium-glucose cotransporter 2 inhibitors (SGLT2is) cause an initial decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM). The effect of different eGFR decline following SGLT2i treatment on risks of atrial fibrillation (AF), cardiovascular, and renal events in patients with T2DM are unknown. Materials and methods We used medical data from a multicenter health care provider in Taiwan and recruited 11 769 T2DM patients with baseline/follow-up eGFR data available after 1-3 months of SGLT2i treatment from June 1, 2016, to December 31, 2018. Patients were followed up from drug index date until the occurrence of adverse clinical events, SGLT2i discontinuation, or the end of the study period, whichever occurred first. Results Overall, SGLT2i treatment was associated with an initial eGFR decline of 3.5% ± 17.0% after a median treatment period of 10 weeks. A total of 37.1%(n = 4371) of patients experienced no eGFR decline, and 30.5%(n = 3593), 20.2%(n = 2376), 8.5%(n = 999), and 3.7%(n = 430) of patients experienced an eGFR decline of 0%-10%, 10%-20%, 20%-30%, and > 30%, respectively. The mean eGFR over time became stable after 6 months in all eGFR decline categories, even in the group with a pronounced eGFR decline of >30%. Compared with no eGFR decline, an initial eGFR decline of 0%-10%, 10%-20%, and 20%-30% was not associated with a higher risk of AF, major adverse cardiovascular events (including ischemic stroke, systemic embolism, and acute myocardial infarction)/heart failure (MACE/HF), and composite renal outcome (doubling of the serum creatinine level/end-stage kidney disease), whereas an eGFR decline of >30% was associated with a higher risk of new-onset AF (adjusted hazard ratio [aHR] = 2.20, 95% confidence interval [CI] = 1.40-3.47]), MACE/HF (aHR = 2.09, 95%CI = 1.04-4.17), and composite renal outcome (aHR = 1.82, 95%CI = 1.18-2.83). The multivariate analysis indicated that the use of diuretic or insulin, presence of stroke, older age, female in gender, a higher HbA1c level, and a lower BMI of 30% following SGLT2i initiation. Conclusions A pronounced eGFR decline >30% following SGLT2i treatment was associated with adverse cardiovascular or renal events among diabetic patients. This article is protected by copyright. All rights reserved.

Aims The frequency of an acute increase in serum creatinine (sCr) of >30%, following treatment of sodium–glucose cotransporter-2 inhibitors (SGLT2is) and its clinical implications in patients with type 2 diabetes remains unclear. Methods and results We used medical data from a multicentre health care provider in Taiwan and recruited 11 657 and 8117 diabetic patients with baseline/follow-up sCr data available within 12 weeks of SGLT2i and dipeptidyl peptidase-4 inhibitor (DPP4i) treatment from 1 June 2016 to 31 December 2018. Participants receiving SGLT2i or DPP4i were categorized by initial sCr change into three groups: >30% sCr increase, 0–30% increase, or no-sCr increase. Participants receiving SGLT2i were associated with a higher proportion of sCr increase of 0–30% (52.7 vs. 42.6%) but a lower proportion of sCr increase of >30% (5.9 vs. 9.6%) when compared with DPP4i. In contrast to DPP4i, the mean estimated glomerular filtration rate over time became stable after 24 weeks in three categories of sCr increase following SGLT2i initiation. Compared with no sCr increase, an initial sCr increase of >30% was associated with a higher risk of major adverse cardiovascular events {adjusted hazard ratio (aHR): 2.91, [95% confidence interval (95% CI):1.37–6.17]}, heart failure hospitalization (HHF) [aHR:1.91, (95% CI:1.08–3.40)], and composite renal outcome [aHR:1.53, (95% CI:1.05–2.25)] in the SGLT2i group; an initial sCr increase of >30% associated with a higher risk of HHF and composite renal outcome in the DPP4i group after multivariate adjustment. Overall, participants receiving SGLT2i were associated with a lower risk of HHF [aHR:0.64, (95% CI:0.48–0.85)] and composite renal outcomes [aHR:0.40, (95% CI:0.34–0.48)] compared with DPP4i after multivariate adjustment, and the treatment benefit was persistent across three categories of sCr increase (P interaction > 0.05). Conclusion A modest increase in serum creatinine (

Aims Recent studies indicated that sodium glucose cotransporter‐2 inhibitors (SGLT2i) reduced heart failure hospitalization in patients with type 2 diabetes mellitus (T2DM). However, whether SGTL2i can improve left ventricular (LV) systolic and diastolic function remained unclear. This study aimed to compare the change in echocardiographic parameters in T2DM patients receiving SGLT2i with a different baseline LV ejection fraction (LVEF). The change in echocardiographic parameters was also compared between T2DM patients treated with SGLT2i and those treated with dipeptidyl peptidase‐4 inhibitor (DPP4i). Methods and results This multicentre cohort study consecutively enrolled 665, 119, and 132 T2DM patients treated with SGLT2i with a preserved (≥50%), moderately reduced (40–50%), and reduced baseline LVEF (

Background: Angiotensin receptor neprilysin inhibitor (ARNI) was recommended by major guidelines as the frontline therapy for heart failure with reduced ejection fraction (HFrEF) since its clinical benefit was proved in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. However, little is known about its safety and effectiveness in real-world practice, often with sicker and more fragile patients. In addition, East Asia population is underrepresented in PARADIGM-HF trial. Methods: We performed a retrospective analysis of patients who received ARNI in 3 medical institutes located in Northern Taiwan. Patients who received a prescription of at least 30 days of ARNI were enrolled. The date of first prescription was defined as the index date, and a period of 12 months preceding the index date was defined as the baseline period. Results: A total of 452 patients were identified (age: 61.9 ± 15.0, male: 79.4%). Compared to PARADIGM-HF populations, our patients had higher values of baseline serum creatinine (mean: 1.5 vs 1.1 mg/dL) and B-type natriuretic peptide (BNP; median: 554.5 vs 255 pg/mL). After 12 months, 41.6% of the patients received less than half of the standard dose. Overall, all-cause death, cardiovascular death, and heart failure readmission rate were 3.0%, 1.1%, and 6.9% in 12 months, respectively. In those who had both baseline and 12-month data, renal function did not change (1.7-1.8 mg/dL, P = .091), left ventricular ejection fraction improved (30.8%-36.8%, P < .001), BNP decreased (777.0-655.8 pg/mL, P = .032), and uric acid decreased (7.5-7.1 mg/dL, P = .009). Conclusion: In our study, patients with HFrEF had higher BNP and serum creatinine level at baseline and had received lower dose of ARNI than the PARADIGM-HF populations. Angiotensin receptor neprilysin inhibitor appeared to be safe as regard renal function and effective in real-world practice. Left ventricular reverse remodeling was observed 1 year after heart failure medication treatment, including ARNI.

Background Sodium–glucose cotransporter 2 inhibitor (SGLT2i) use reduces body weight (BW) in patients with type 2 diabetes mellitus (T2DM). Obesity and T2DM are strong risk factors of new-onset atrial fibrillation (AF). However, whether BW loss following SGLT2i treatment reduces AF risk in patients with T2DM remains unclear. Methods We used a medical database from a multicenter health care provider in Taiwan, which included 10,237 patients with T2DM, from June 1, 2016 to December 31, 2018, whose BW data at baseline and at 12 weeks of SGLT2i treatment were available. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the SGLT2i, or the end of the study period, whichever occurred first. Results The patients’ baseline body mass index (BMI) was 28.08 $$\pm$$ ± 4.88 kg/m2. SGLT2i treatment was associated with a BW loss of 1.35 $$\pm$$ ± 3.28 kg (1.78%$$\pm$$ ± 4.47%). There were 37.4%, 47.0%, and 15.6% of patients experienced no-BW loss (n = 3832), BW loss 0.0–4.9% (n = 4814), and $$\ge$$ ≥ 5.0% (n = 1591) following SGLT2i treatment, respectively. Compared with patients with baseline BMI 2, AF risk significantly increased in patients with baseline BMI $$\ge$$ ≥ 27.5 kg/m2 (P for trend = 0.015). Compared with those without BW loss after SGLT2i treatment, AF risk significantly decreased with a BW loss of $$\ge$$ ≥ 5.0% (adjusted hazard ratios [95% confidence intervals]: 0.39[0.22–0.68]). Use of diuretics, old age, high-dose SGLT2i, higher estimated glomerular filtration rate, and baseline BMI were independent factors associated with a BW loss of $$\ge$$ ≥ 5.0% following SGLT2i initiation. By contrast, neither baseline BMI nor BW loss after SGLT2i treatment predicted major cardiovascular adverse events or heart failure hospitalization risk (P for trend > 0.05). Conclusion BW loss of ≥ 5.0% following SGLT2i treatment was associated with a lower risk of new-onset AF in patients with T2DM in real-world practice.

BackgroundSodium glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitor (DPP4i) among a longitudinal cohort of diabetic patients.MethodsWe used medical data from a multi-center healthcare provider in Taiwan, which included a total of 15,606 and 12,383 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first.ResultsOverall, 55%, 45%, and 0% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (5%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [hazard ratio: 0.61; 95% confidential interval: 0.50–0.73;P $$\ge$$≥8%, and chronic kidney disease. The advantage of SGLT2i over DPP4i persisted with different SGLT2i (dapagliflozin or empagliflozin) and either low- or standard-dose SGLT2i.ConclusionsSGLT2i was associated with a lower risk of new-onset AF compared with DPP4i among T2DM patients in real-world practice.

In this paper, we demonstrated the hybrid silicon photonics platform developed in ITRI. The functions of this platform include full-wafer high speed photonic measurement, active and passive device fabrication, and the photonic packaging technology.

This research presents the design and characterization of the traveling wave Mach Zehnder modulator loaded L-shaped PN junction phase shifter at 72.8 Gbps data-rate. We propose a new structure of phase shifter with low series resistance meanwhile maintaining the FOM with low V π L (0.9 V-cm) and optical absorption.

We present a special design and the characterization of racetrack-coupled Mach_Zehnder interferometer for high speed and high linearity E/O modulation. The static extinction ratio, and full-widthhalf-maximum are analyzed and the photon-life-time-limited bandwidth are evaluated for more than 50 GHz.

Aims This study aimed to compare the efficacy of angiotensin receptor–neprilysin inhibitor (ARNI) therapy with angiotensin receptor blocker (ARB) therapy for cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction. Methods and results Data were obtained from the Chang Gung Research Database. The cohort entry date of the ARB group was assigned as that of the ARNI group to avoid immortal time bias. Additionally, 1:1 propensity score matching based on age, sex, and baseline left ventricular ejection fraction was conducted. The expectation–maximization imputation method with inverse probability of treatment weighting was used to compare outcomes between the two groups. The primary outcome was a composite of cardiovascular death and hospitalization for worsening HF. Patients who received ARNI therapy had a significantly lower risk of the primary composite outcome occurring than patients who received ARBs (hazard ratio, 0.74; 95% confidence interval, 0.57–0.96). The reduction of hospitalization for worsening HF contributed most to the primary outcome benefits. In addition to the primary outcome, the ARNI group had a significantly lower risk of non‐fatal myocardial infarction. The improvement of ejection fraction was not significantly different between the groups. The medication doses of ARNI were lower than in clinical trials. Conclusions In patients with HF with reduced ejection fraction, sacubitril/valsartan was superior to ARB therapy in reducing the occurrence of the primary outcome endpoint of hospitalization for worsening HF and cardiovascular death.

Network Function Virtualization (NFV) allows datacenters to consolidate network appliance functions onto commodity servers and devices. Currently telecommunication carriers are re-architecting their central offices as NFV datacenters that, along with SDN, help network service providers to speed deployment and reduce cost. However, it is still unclear how a carrier network shall organize its NFV datacenter resources into a coherent service architecture to support global network functional demands. This work proposes a hierarchical NFV/SDN-integrated architecture in which datacenters are organized into a multi-tree overlay network to collaboratively process user traffic flows. The proposed architecture steers traffic to a nearby datacenter to optimize user-perceived service response time. Our experimental results reveal that the 3-tier architecture is favored over others as it strikes a good balance between centralized processing and edge computing, and the resource allocation should be decided based on traffic's source-destination attributes. Our results indicate that when most traffic flows within the same edge datacenter, the strategy whereby resources are concentrated at the carrier's bottom-tier datacenters is preferred, but when most traffic flows across a carrier network or across different carrier networks, a uniform distribution over the datacenters or over the tiers, respectively, stands out from others.

Background Patterns of scapular dyskinesis have unique scapular kinematics and associated muscular activation. The characteristics of unique dyskinesis patterns may be associated with functional disability. Objectives To investigate whether the shoulder function level and primary dysfunction items were different in unique dyskinesis pattern. The factors associated with shoulder dysfunction in different dyskinesis patterns were identified. Design Cross-sectional study. Methods Fifty-one participants with unilateral shoulder pain were classified as having a single dyskinesis pattern (inferior angle prominence, pattern I; medial border prominence, pattern II) or a mixed dyskinesis pattern (patterns I + II). Clinical measurements with the Flexilevel Scale of Shoulder Function (FLEX-SF), shoulder range of motion and pectoralis minor index were recorded. These clinical measurements, 3-D scapular kinematics (electromagnetic-based motion analysis), and associated muscular activation (electromyography on the upper/middle/lower trapezius and serratus anterior muscles) during arm elevation were analyzed for associations with functional disability. Results We found FLEX-SF scores and primary dysfunction items were similar among the patterns of dyskinesis. In inferior angle prominence, increased shoulder function was associated with decreased upper trapezius activity (R 2 = 0.155, p = 0.035), which accounted for approximately 16% of the variance of FLEX-SF scores. In medial border prominence, increased shoulder function was associated with increased lower trapezius activity (R 2 = 0.131, p = 0.017), which accounted for approximately 13% of the variance of FLEX-SF scores. Conclusion Upper and lower trapezius activities are important to consider in the evaluation of patients with pattern I and II, respectively. No other factors were related to shoulder dysfunction due to insufficient challenge of arm elevation tasks.

We successfully establish a silicon photonics device manufacturing and testing platform in 200mm SOI wafer. We integrate modulator and driver chip to show 30Gb/s PAM4 capability. A fully-automatic wafer level characterization process is built up for all optical devices in surface coupling method.

Einstein-Podolsky-Rosen (EPR) steering is the explicit demonstration of the fact that the measurements of one party can in influence the quantum state held by another, distant, party, and do so even if the measurements themselves are untrusted. This has been shown to allow one-sided device-independent quantum-information tasks between two remote parties. However, in general, advanced multiparty protocols for generic quantum technologies, such as quantum secret sharing and blind quantum computing for quantum networks, demand multipartite quantum correlations of graph states shared between more than two parties. Here, we show that, when one part of a quantum multidimensional system composed of a two-colorable graph state (e.g., cluster and Greenberger-Horne-Zeilinger states) is attacked by an eavesdropper using a universal cloning machine, only one of the copy subsystems can exhibit multipartite EPR steering but not both. Such a no-sharing restriction secures both state sources and channels against cloning-based attacks for generic quantum networking tasks, such as distributed quantum-information processing, in the presence of uncharacterized measurement apparatuses., Accepted for publication in Physical Review A

Quantum networks illustrate the use of connected nodes of quantum systems as the backbone of distributed quantum information processing. When the network nodes are entangled in graph states, such a quantum platform is indispensable to almost all the existing distributed quantum tasks. Unfortunately, real networks unavoidably suffer from noise and technical restrictions, making nodes transit from quantum to classical at worst. Here, we introduce a figure of merit in terms of the number of classical nodes for quantum networks in arbitrary graph states. Such a network property is revealed by exploiting a novel Einstein-Podolsky-Rosen steerability. Experimentally, we demonstrate photonic quantum networks of ${n}_{q}$ quantum nodes and ${n}_{c}$ classical nodes with ${n}_{q}$ up to 6 and ${n}_{c}$ up to 18 using spontaneous parametric down-conversion entanglement sources. We show that the proposed method is faithful in quantifying the classical defects in prepared multiphoton quantum networks. Our results provide novel identification of generic quantum networks and nonclassical correlations in graph states.

BackgroundPrevious studies indicated low-intensity warfarin (INR target of 1.5-2.5) achieved reduced hemorrhage without increasing thromboembolism for Asians with non-valvular atrial fibrillation (NVAF). Whether non-vitamin K antagonist oral anticoagulant (NOAC) is superior to warfarin with good time in the therapeutic range (TTR) based on lower INR target among Asians with NVAF remains unknown.MethodsIn this retrospective study collected from Taiwan Chang Gung Memorial Hospital Database, there were 5,197, 3,396, and 9,898 consecutive patients taking warfarin, NOAC, and no-treatment, respectively, from January 1, 2000 to December 31, 2015. Propensity-score weighting was used across the study groups. Patients were followed until the first occurrence of study outcome or end date of study.ResultsAmong those patients taking warfarin, the mean"artificial" TTR (aTTR) based on a lower INR target of 1.5-2.5 was 44.4±33.3%. Total 79.2% (n = 2,690) patients took low-dose NOACs. Patients with aTTR in the range from 70%(24.9%) showed decremental risks of efficacy and composite outcome compared with no-treatment. The risk of major bleeding didn't increase among patients with top aTTR>70% compared to no-treatment. The NOAC group showed a comparable risk of composite outcome to the warfarin subgroup with aTTR of >70% (P = 0.485). The NOAC group had a lower risk of composite outcome than warfarin subgroup with TTR of>70% based on the INR target of 2.0-3.0 (P = 0.004).ConclusionsNOACs showed a comparable risk of efficacy, safety, and composite outcome to well-managed warfarin based on a lower INR target of 1.5-2.5 in Asians with NVAF taking oral anticoagulants.

Background Knowledge of the kinematics and associated muscular activity in individuals with scapular dyskinesis may provide insight into the injury mechanism and inform the planning of treatment strategies. We investigated scapular kinematics and associated muscular activation during arm movements in individuals with scapular dyskinesis. Methods A visual-based palpation method was used to evaluate 82 participants with unilateral shoulder pain. Scapular movements during arm raising/lowering movements were classified as abnormal single pattern (inferior angle prominence, pattern I; medial border prominence, pattern II; excessive/inadequate scapular elevation or upward rotation, pattern III), abnormal mixed patterns, or normal pattern (pattern IV). Scapular kinematics and associated muscular activation were assessed with an electromagnetic motion-capturing system and surface electromyography. Results More scapular internal rotation was found in pattern II subjects (4°, P = .009) and mixed pattern I and II subjects (4°, P = .023) than in control subjects during arm lowering. Scapular posterior tipping (3°, P = .028) was less in pattern I subjects during arm lowering. Higher upper trapezius activity (14%, P = .01) was found in pattern II subjects during arm lowering. In addition, lower trapezius (5%, P = .025) and serratus anterior activity (10%, P = .004) were less in mixed pattern I and II subjects during arm lowering. Conclusions Specific alterations of scapular muscular activation and kinematics were found in different patterns of scapular dyskinesis. The findings also validated the use of a comprehensive classification test to assess scapular dyskinesis, especially in the lowering phase of arm elevation.

Physical activities are recommended to reduce neuropsychiatric symptoms of nursing home residents with mild dementia. However, relevant information is not available for community-dwelling persons with cognitive impairment. Therefore, this cross-sectional study examined the effects of leisure-time physical activities on cognitively impaired persons' neuropsychiatric symptoms and their family caregivers' distress. Activities were described in terms of their frequency, duration, number of different types, and energy expenditure. Participants were 58 dyads of persons with cognitive impairment and their family caregivers. Data on leisure-time physical activities and neuropsychiatric symptoms were collected using a 7-Day Physical Activity Recall and Chinese Neuropsychiatric Inventory, respectively. The most frequently reported activity was strolling (70.7%). The mean weekly activity frequency, duration, and energy expenditure were 4.52 (SD = 4.27) times, 3.7 (SD = 4.38) h, and 771.47 (SD = 886.38) kcal, respectively. The number of different activity types negatively and significantly predicted cognitively impaired persons' mood and psychosis as well as family caregivers' distress.

Background People with cognitive impairment have been shown to engage in few structured activities. During periods of unoccupied time or boredom, these patients most likely manifest neuropsychiatric symptoms. Objective The purposes of this study were to (1) describe the leisure-activity indicators (variety in leisure activities, appraisal of each activity's restorative function, and leisure dysfunction, i.e. failure to appreciate the importance of restorative aspects of leisure activity), of community-dwelling older Taiwanese adults with cognitive impairment, and (2) explore the relationships between these indicators and neuropsychiatric symptoms in this population. Design Cross-sectional. Setting Memory disorder and geriatric psychiatric clinics of two hospitals in northern Taiwan. Participants Patient-family caregiver dyads ( N =60). Method Patients' dementia severity, based on Clinical Dementia Rating scores, was 0.5–2.0. Family caregivers completed the Chinese Neuropsychiatric Inventory to assess patients' behavioral problems and the Restorative Activity Questionnaire to assess patients' participation in leisure activities, restorative experience, and leisure dysfunction. Results On average, patients participated in approximately five individual leisure activities, but very few group leisure activities. The top three leisure activities were watching TV, taking a walk, and talking to relatives and friends. The leisure activities in which participants least commonly engaged were fishing, attending cultural exhibitions, and chess/card playing. All leisure-activity indicators were significantly correlated with disease stage, global cognitive function, and neuropsychiatric symptoms. Two leisure-activity indicators (leisure dysfunction and restorative experiences) were significantly correlated with depressive symptoms. Only leisure dysfunction significantly and consistently predicted neuropsychiatric symptoms. Conclusion These results can be used by home health or community health nurses to design tailored leisure-activity plans for improving the care quality of patients with cognitive impairment. Health professionals can develop leisure-education programmes to emphasize the value of leisure pursuit and to modify attitudes toward participating in leisure activities. Finally, parks and recreational agencies may re-examine their services and facilities to meet the increasing needs of this population.