Taiwan's National Health Insurance Research Database (NHIRD) exemplifies a population-level data source for generating real-world evidence to support clinical decisions and health care policy-making. ...Like with all claims databases, there have been some validity concerns of studies using the NHIRD, such as the accuracy of diagnosis codes and issues around unmeasured confounders. Endeavors to validate diagnosed codes or to develop methodologic approaches to address unmeasured confounders have largely increased the reliability of NHIRD studies. Recently, Taiwan's Ministry of Health and Welfare (MOHW) established a Health and Welfare Data Center (HWDC), a data repository site that centralizes the NHIRD and about 70 other health-related databases for data management and analyses. To strengthen the protection of data privacy, investigators are required to conduct on-site analysis at an HWDC through remote connection to MOHW servers. Although the tight regulation of this on-site analysis has led to inconvenience for analysts and has increased time and costs required for research, the HWDC has created opportunities for enriched dimensions of study by linking across the NHIRD and other databases. In the near future, researchers will have greater opportunity to distill knowledge from the NHIRD linked to hospital-based electronic medical records databases containing unstructured patient-level information by using artificial intelligence techniques, including machine learning and natural language processes. We believe that NHIRD with multiple data sources could represent a powerful research engine with enriched dimensions and could serve as a guiding light for real-world evidence-based medicine in Taiwan.
It has been widely reported that ketamine rescues chronic stress-induced depression-like behavior, but the underlying cellular mechanisms of the rapid antidepressant actions of ketamine remain ...largely unclear. Both male and female Sprague-Dawley rats were used and received modified learned helplessness paradigm to induce depression-like behavior. Depression-like behavior was assayed and manipulated using forced swim tests, sucrose preference tests and pharmacological microinjection. We conducted whole-cell patch-clamp electrophysiological recordings in the midbrain ventrolateral periaqueductal gray (vlPAG) neurons. Surface and cytosolic glutamate receptor 1 (GluR1) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression were analyzed using Western blotting. Phosphorylated GluR1 expression was quantified using Western blotting analysis. The results showed that a single systemic administration of a ketamine metabolite (2R,6R)-hydroxynorketamine (2R,6R-HNK) rapidly rescued chronic stress-induced depression-like behavior and persisted for up to 21 days. Consistently, the chronic stress-induced diminished glutamatergic transmission and surface GluR1 expression in the vlPAG were also reversed by a single systemic injection of (2R,6R)-HNK. Furthermore, bath application of (2R,6R)-HNK increased the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in the vlPAG. Further evidence for the antidepressant action of (2R,6R)-HNK is provided by the finding that microinjection of (2R,6R)-HNK into the vlPAG exhibited a rapid-acting and long-lasting antidepressant effect. This antidepressant effect of (2R,6R)-HNK was prevented by the intra-vlPAG microinjection of AMPA receptor antagonist CNQX. Together, the current results provide evidence that (2R,6R)-HNK rescues chronic stress-induced depression-like behavior with rapid-acting and long-lasting antidepressant effects through enhancement of AMPA receptor-mediated transmission in the vlPAG.
•Both intraperitoneal and intra-vlPAG administration of (2R,6R)-HNK rescue chronic stress-induced depression-like behavior.•(2R,6R)-HNK rapidly rescues chronic stress-induced depression-like behavior.•Antidepressant effects of (2R,6R)-HNK persist for up to 21 days.•(2R,6R)-HNK increases glutamate release presynaptically and surface GluR1 expression postsynaptically in the vlPAG.•Blockage of AMPAR in the vlPAG antagonizes antidepressant effects of (2R,6R)-HNK.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The validity of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding for the identification of acute ischemic stroke (AIS) in Taiwan's National ...Health Insurance claims database has not been investigated. This study aimed to construct and validate the case definition algorithms for AIS based on ICD-10-CM diagnostic codes.
This study identified all hospitalizations with ICD-10-CM code of I63* in any position of the discharge diagnoses from the inpatient claims database and all patients with a final diagnosis of AIS from the stroke registry between Jan 2018 and Dec 2019. Hospitalizations in the claims data that could be successfully linked to those in the registry data were regarded as true episodes of AIS. Otherwise, their electronic medical records and images were manually reviewed to ascertain whether they were true episodes of AIS. Using the true episodes of AIS as the reference standard, the positive predictive value (PPV) and sensitivity of various case definition algorithms for AIS were calculated.
A total of 1227 hospitalizations were successfully linked. Among the 155 hospitalizations that could not be linked, 54 were determined to be true episodes of AIS. Using ICD-10-CM code of I63* in any position of the discharge diagnoses to identify AIS yielded a PPV and sensitivity of 92.7% and 99.4%, respectively. The PPV increased to 99.8% with >12% decrease in the sensitivity when AIS was restricted to those with I63* as the primary diagnosis. When AIS was defined to be I63* as the primary, first secondary, or second secondary diagnosis, both PPV and sensitivity were greater than 97%.
This study demonstrated the validity of various case definition algorithms for AIS based on ICD-10-CM coding and can provide a reference for future claims-based stroke research.
With the advent of exploration in finding new sources for treating different diseases, one possible natural source is from marine algae. Having an array of potential benefits, researchers are ...interested in the components which comprise one of these activities. This can lead to the isolation of active compounds with biological activities, such as antioxidation of free radicals, anti-inflammation, antiproliferation of cancer cells, and anticoagulant to name a few. One of the compounds that are isolated from marine algae are sulfated polysaccharides (SPs). SPs are complex heterogenous natural polymers with an abundance found in different species of marine algae. Marine algae are known to be one of the most important sources of SPs, and depending on the species, its chemical structure varies. This variety has important physical and chemical components and functions which has gained the attention of researchers as this contributes to the many facets of its pharmacologic activity. In this review, recent pharmacologic application potentials and updates on the use of SPs from marine algae are discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
Epidemiological data regarding antipsychotic initiation in elderly patients with stroke are limited. We aimed to investigate the incidence, prescription patterns and determinants of ...antipsychotic initiation in elderly patients with stroke.
Methods
We conducted a retrospective cohort study to identify patients aged above 65 years who had been admitted for stroke from the National Health Insurance Database (NHID). The index date was defined as the discharge date. The incidence and prescription pattern of antipsychotics were estimated using the NHID. To evaluate the determinants of antipsychotic initiation, the cohort identified from the NHID was linked to the Multicenter Stroke Registry (MSR). Demographics, comorbidities and concomitant medications were obtained from the NHID. Information including smoking status, body mass index, stroke severity and disability was retrieved by linking to the MSR. The outcome was antipsychotic initiation after the index date. Hazard ratios for antipsychotic initiation were estimated using the multivariable Cox model.
Results
In terms of prognosis, the first 2 months after a stroke was the highest‐risk period for antipsychotic use. A high burden of coexisting diseases carried an increased risk of antipsychotic use; in particular, chronic kidney disease (CKD) had the highest adjusted hazard ratio (aHR = 1.73; 95% CI 1.29–2.31) as compared with other risk factors. Furthermore, stroke severity and disability were significant risk factors for antipsychotic initiation.
Conclusions
Our study indicated that elderly stroke patients with chronic medical conditions, particularly CKD, and a higher stroke severity and disability were at greater risk of psychiatric disorders during the first 2 months after a stroke.
Clinical trial registration: NA.
Key points
First 2 months after stroke carry the highest risk of antipsychotic initiation.
Most commonly‐prescribed antipsychotic was quetiapine in elderly stroke patients.
Chronic kidney disease carries the greatest antipsychotic initiation risk.
Greater stroke severity/disability lead to a higher antipsychotic initiation risk.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background/purpose The National Health Insurance Research Database, which uses claims data from hospitals contracted with the National Health Insurance (NHI) program in Taiwan, has been widely used ...for stroke research. The diagnostic accuracy of the NHI claims data with regard to acute ischemic stroke (AIS) has rarely been validated. The aim of this study was to validate the diagnosis of AIS in NHI claims data using the Taiwan Stroke Registry (TSR) as a reference. Methods We retrieved patients' data with a discharge diagnosis of AIS five-digit International Classification of Diseases Code, 9th version (ICD-9 code): 433 xx or 434 xx in a single medical center from August 2006 to December 2008. We then linked these patients to the TSR to validate their AIS diagnosis in the claims data. The positive predictive value (PPV) and sensitivity were determined. Results We reviewed the claims data of 1736 consecutive AIS patients, of whom 1299 (74.8%) were linked successfully to the stroke registry database. After reviewing the medical records and imaging results of other patients not linked to the registry database ( n = 437), 235 patients were found to have had an AIS. The PPV was 88.4% 95% confidence interval (CI): 86.8–89.8% and sensitivity was 97.3% (95% CI: 96.4–98.1%). Forty-four (21.8%) of the false-positive cases ( n = 202) were coded as 433 x 0 or 434 x 0. Conclusion The PPV of a diagnosis of AIS in the NHI claims data was high. Using five-digit ICD-9 codes to identify AIS cases will markedly decrease the false-positive rate compared with using the commonly used three-digit method.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Atrial fibrillation (AF) can be newly detected in approximately one-fourth of patients with ischemic stroke and transient ischemic attack without previously recognized AF. We present updated evidence ...supporting that AF detected after stroke or transient ischemic attack (AFDAS) may be a distinct clinical entity from AF known before stroke occurrence (known atrial fibrillation). Data suggest that AFDAS can arise from the interplay of cardiogenic and neurogenic forces. The embolic risk of AFDAS can be understood as a gradient defined by the prevalence of vascular comorbidities, the burden of AF, neurogenic autonomic changes, and the severity of atrial cardiopathy. The balance of existing data indicates that AFDAS has a lower prevalence of cardiovascular comorbidities, a lower degree of cardiac abnormalities than known atrial fibrillation, a high proportion (52%) of very brief (<30 seconds) AF paroxysms, and is more frequently associated with insular brain infarction. These distinctive features of AFDAS may explain its recently observed lower associated risk of stroke than known atrial fibrillation. We present an updated ad-hoc meta-analysis of randomized clinical trials in which the association between prolonged cardiac monitoring and reduced risk of ischemic stroke was nonsignificant (incidence rate ratio, 0.90 95% CI, 0.71-1.15). These findings highlight that larger and sufficiently powered randomized controlled trials of prolonged cardiac monitoring assessing the risk of stroke recurrence are needed. Meanwhile, we call for further research on AFDAS and stroke recurrence, and a tailored approach when using prolonged cardiac monitoring after ischemic stroke or transient ischemic attack, focusing on patients at higher risk of AFDAS and, more importantly, at higher risk of cardiac embolism.
Background
The early stage of the COVID‐19 pandemic was a critical time for increasing loneliness, especially for older people. However, there is insufficient existing research on associated ...interventions and their effectiveness.
Aim
This study aimed to investigate the effectiveness of an 8‐week online interactive course on the loneliness, depression, social support, and quality of life (QOL) of older adults in the community during the COVID‐19 pandemic.
Methods
A single‐blind randomized controlled trial was conducted to collect data from a community in Taiwan. Eighty‐nine participants recruited from long‐term care institutions were randomly divided into an experimental group (n = 44) and a control group (n = 45). Participants in the experimental group received an 8‐week (Monday to Friday) intensive online interactive course, whereas those in the control group watched 8 weeks (Monday to Friday) of unidirectional online video programs.
Results
Significant differences were observed in the UCLA Loneliness Scale and in both the psychological health and social relationship domains of the WHO Quality of Life‐BREF Scale. In other words, compared with those in the control group, participants in the experimental group experienced more significant improvements in the state of their loneliness as well as QOL in the psychological health and social relationship domains (without the physical health/environment domains) after taking the online interactive course.
Conclusions
The results of this study showed that the 8‐week online interactive course could effectively improve the loneliness, the psychological health domain, and the social relationship domain of the QOL of the older adults of a particular community during the ongoing pandemic. Geriatr Gerontol Int 2023; 23: 91–97.
•Bidirectional interactive activities have a better efficacy in reducing loneliness and improving quality of life.
•Online social support may help to alleviate loneliness and isolation, making it an appropriate solution in this ongoing pandemic situation.
•The 8‐week intensive online interactive course successfully improved loneliness and improved quality of life during the ongoing COVID‐19 pandemic.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Chronic kidney disease (CKD) is an independent risk factor for stroke and covert cerebrovascular disease, and up to 40% of stroke patients have concomitant CKD. However, the so-called "cerebrorenal ...interaction" attracted less attention compared to its cardiorenal counterpart. Diabetes is the leading cause of CKD. The sodium-glucose cotransporter (SGLT) 2 inhibitor is a relatively new class of oral anti-diabetic drugs and has cardiorenal benefits in addition to glucose-lowering effects. In the present perspective, we would like to review the current status and future potential of the SGLT2 inhibitor in cerebro-renal interactions and strokes regardless of the status of diabetes. We propose the potential roles of baseline renal functions and SGLT1/2 dual inhibition in stroke prevention, as well as the additional benefits of reducing atrial fibrillation and hemorrhagic stroke for SGLT2 inhibitors. Further clinical trials are anticipated to test whether SGLT2 inhibitors can fulfill the long-standing unmet clinical need and stop such a vicious cycle of cerebro-renal interaction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Many artificial intelligence (AI) edge devices use nonvolatile memory (NVM) to store the weights for the neural network (trained off-line on an AI server), and require low-energy and fast I/O ...accesses. The deep neural networks (DNN) used by AI processors 1,2 commonly require p-layers of a convolutional neural network (CNN) and q-layers of a fully-connected network (FCN). Current DNN processors that use a conventional (von-Neumann) memory structure are limited by high access latencies, I/O energy consumption, and hardware costs. Large working data sets result in heavy accesses across the memory hierarchy, moreover large amounts of intermediate data are also generated due to the large number of multiply-and-accumulate (MAC) operations for both CNN and FCN. Even when binary-based DNN 3 are used, the required CNN and FCN operations result in a major memory I/O bottleneck for AI edge devices.
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