Perturbations of Telmisartan Alone and in Combination with Ranolazineor Dapagliflozin on the Amplitude and Gating of Voltage-gated Na + Current in Neuroblastoma Neuronal Cells.

A recent study investigated the correlation between telmisartan (TEL) exposure and Alzheimer's disease (AD) risk among African Americans (AAs) and European Americans. Their findings indicated that moderate-to-high TEL exposure was linked to a decreased incidence of AD among AAs. These results suggest a potential association between TEL and a reduced risk of AD specifically within the AA population. Here, we investigated the effects of TEL, either alone or in combination with ranolazine (Ran) or dapagliflozin (Dapa), on voltage-gated Na + currents ( INa ) in Neuro-2a cells. TEL, primarily used for treating hypertension and cardiovascular disorders, showed a stimulatory effect on INa , while Ran and Dapa reversed this stimulation. In Neuro-2a cells, we demonstrated that with exposure to TEL, the transient ( INa(T) ) and late ( INa(L) ) components of INa were differentially stimulated with effective EC 50 's of 16.9 and 3.1 µM, respectively. The research implies that TEL's impact on INa might be associated with enhanced neuronal excitability. This study highlights the complex interplay between TEL, Ran, and Dapa on INa and their potential implications for AD, emphasizing the need for further investigation to understand the mechanisms involved.

Clinimetric properties of the "FIND-NEEDS" to screen geriatric conditions.

INTRODUCTION: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic "FIND-NEEDS" was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS. METHODS: First-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC). RESULTS: The mean age of the 114 outpatients was 78.3±7.6 years, and 79(69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r=0.494; p<0.001), and the binary score showed excellent correlation (r=0.944; p<0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90). DISCUSSION/CONCLUSION: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards.

Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.

Fear, Stress, Susceptibility, and Problematic Social Media Use Explain Motivation for COVID-19 Preventive Behaviors Among Patients With Stroke and Their Caregivers.

The COVID-19 pandemic presented significant challenges for individuals who experienced stroke and their caregivers. It is essential to understand the factors affecting preventive behavior in these populations. Therefore, the present study examined the factors that influenced COVID-19 preventive behavior and motivation for COVID-19 vaccine uptake among patients with stroke and their caregivers. A cross-sectional study comprising 191 participants (81 patients with stroke and 110 caregivers) was carried out. Participants completed a survey assessing fear of COVID-19, stress, perceived susceptibility, problematic social media use, preventive behaviors, and motivation for vaccine uptake. Statistical analyses included descriptive statistics, Pearson correlations, and multiple linear regressions. Motivation for COVID-19 vaccine uptake was significantly positively correlated with problematic social media use (r = 0.225, P = .002), perceived susceptibility (r = 0.197, P = .008), and fear of COVID-19 (r = 0.179, P = .015), but negatively correlated with stress (r = -0.189, P = .010). Caregivers, compared to patients, showed a lower level of preventive behavior (standardized coefficient = -0.23, P = .017). Furthermore, higher levels of fear were associated with increased preventive behavior (standardized coefficient = 0.22, P = .006), while greater stress correlated with lower preventive behavior (standardized coefficient = -0.38, P < .001). Among patients with stroke and their caregivers, motivation of COVID-19 vaccine uptake and preventive behaviors were influenced by factors such as fear, perceived susceptibility, social media use, and stress. By using strategies such as targeted education, support, and communication campaigns, healthcare providers and policymakers may be able to enhance the well-being of patients with stroke and their caregivers during future pandemics.

The association of care burden with motivation of vaccine acceptance among caregivers of stroke patients during the COVID-19 pandemic: mediating roles of problematic social media use, worry, and fear.

BACKGROUND: The aim of the present study was to investigate the relationship between care burden and motivation of COVID-19 vaccine acceptance among caregivers of patients who have experienced a stroke and to explore the mediating roles of social media use, fear of COVID-19, and worries about infection in this relationship. METHODS: A cross-sectional survey study with 172 caregivers of patients who had experienced a stroke took part in a Taiwan community hospital. All participants completed the Zarit Burden Interview, Bergen Social Media Addiction Scale, Worry of Infection Scale, Fear of COVID-19 Scale, and Motors of COVID-19 Vaccine Acceptance Scale. Multiple linear regression model was applied to construct and explain the association among the variables. Hayes Process Macro (Models 4 and 6) was used to explain the mediation effects. RESULTS: The proposed model significantly explained the direct association of care burden with motivation of COVID-19 vaccine acceptance. Despite the increased care burden associated with decreased vaccine acceptance, problematic social media use positively mediated this association. Moreover, problematic social media use had sequential mediating effects together with worry of infection or fear of COVID-19 in the association between care burden and motivation of vaccine acceptance. Care burden was associated with motivation of vaccine acceptance through problematic social media use followed by worry of infection. CONCLUSIONS: Increased care burden among caregivers of patients who have experienced a stroke may lead to lower COVID-19 vaccines acceptance. Moreover, problematic social media use was positively associated with their motivation to get COVID-19 vaccinated. Therefore, health experts and practitioners should actively disseminate accurate and trustworthy factual information regarding COVID-19, while taking care of the psychological problems among caregivers of patients who have experienced a stroke.

Using an In-Sample Addition of Medronic Acid for the Analysis of Purine- and Pyrimidine-Related Derivatives and Its Application in the Study of Lung Adenocarcinoma A549 Cell Lines by LC-MS/MS.

Intracellular purine- and pyrimidine-related derivatives are vital molecules for preserving genetic information and are essential for cellular bioenergetics and signal transduction. This study developed a practical liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying intracellular purine- and pyrimidine-related derivatives. To solve the distorted peak shape related to di- and triphosphate nucleotides, in-sample addition of medronic acid and ammonium phosphate was performed. Using the BEH-amide column, the results showed that adding 0.5 mM medronic acid to the sample significantly improved the peak shape without causing an obvious ion suppressive effect. Method validation confirmed that the coefficients of determination (R2) values for linearity evaluation were above 0.94 for all analytes. The intraday and interday accuracies ranged from 85.1 to 128.4%, with the precision below 16.6%. The validated method was successfully applied in characterizing the alterations of purine- and pyrimidine-related derivatives in the A549 cell line with perturbed mitochondrial fission or blockade of the electron transport chain. Collectively, this study demonstrates that the strategy of in-sample medronic acid addition is effective in improving the quantification of intracellular purine- and pyrimidine-related derivatives. We believe that our proposed platform can facilitate the development of novel drugs targeting purine and pyrimidine metabolism in the future.

Examining the association between neuropsychiatric symptoms among people with dementia and caregiver mental health: are caregiver burden and affiliate stigma mediators?

BACKGROUND: Neuropsychiatric disturbances are common manifestations of dementia disorders and are associated with caregiver burden and affiliate stigma. The present study investigated affiliate stigma and caregiver burden as mediators for the association between neuropsychiatric symptoms of people with dementia (PWD) and caregiver mental health such as depression and anxiety. METHODS: A cross-sectional survey study was carried out with 261 dyads of PWD and informal caregivers from the outpatient department of a general hospital in Taiwan. The survey included the Caregiver Burden Inventory (CBI), the Affiliate Stigma Scale (ASS), the Taiwanese Depression Questionnaire (TPQ), and the Beck Anxiety Inventory (BAI). Mediation models were tested using the Hayes' PROCESS macro (Model 4 for parallel mediation model; Model 6 for sequentially mediation model). RESULTS: Caregiver burden, affiliate stigma, caregiver depression, and caregiver anxiety were significantly associated with neuropsychiatric symptoms. After controlling for several potentially confounding variables, it was found that PWD's neuropsychiatric symptoms, caregiver burden and affiliate stigma significantly explained 52.34% of the variance in caregiver depression and 37.72% of the variance in caregiver anxiety. The parallel mediation model indicated a significantly indirect path from PWD's neuropsychiatric symptoms to caregiver mental health through caregiver burden and affiliate stigma, while the direct effect was not significant. Moreover, there was a directional association between caregiver burden and affiliate stigma in the sequential mediation model. CONCLUSIONS: These findings show that it is imperative to improve caregivers' perception of those with dementia to reduce internalized stigma and to improve caregivers' mental health. Implementation of affiliate stigma assessment in clinical practice would allow distinctions to be made between the impact of affiliate stigma and the consequences of caregiver burden to help inform appropriate intervention.

Burdens on caregivers of patients with stroke during a pandemic: relationships with support satisfaction, psychological distress, and fear of COVID-19.

BACKGROUND: Caregivers have faced unprecedented circumstances throughout the COVID-19 pandemic, but previous research only minimally addresses the caregivers' burden. Therefore, this study aimed to investigate the relationship between caregiver burden, psychological stress, satisfaction with support, and fear of COVID-19 in caregivers of patients with stroke during the pandemic. METHODS: A cross-sectional survey study with total of 171 caregivers of patients with stroke in a community hospital in Taiwan. All participants completed the Zarit Burden Interview, Depression, Anxiety, Stress Scale (DASS-21), satisfaction of support survey, and Fear of COVID-19 Scale. Pearson correlations were used to examine the bivariate correlations between study variables. Then, with the control of demographic confounders, a multiple linear regression model was applied with significant variables to construct and explain caregiver burden. RESULTS: The proposed model significantly explained the caregiver burden of caregivers of patients with stroke. Specifically, the caregiver burden was negatively correlated with satisfaction with family support, but positively with psychological distress and the fear of COVID-19. CONCLUSIONS: Caregivers of patients with stroke will suffer a greater burden if they have lower satisfaction with family support, experienced higher psychological distress, and perceived more fear of the COVID-19 pandemic. Health professionals must address these concerns, support caregivers, and enhance available resources.

Simvastatin Attenuated Tumor Growth in Different Pancreatic Tumor Animal Models.

Newly diagnosed pancreatic cancer increases year by year, while the prognosis of pancreatic cancer has not been very good. Statin drugs were found to have protective effects against a variety of cancers, but their association with pancreatic cancer remains to be clarified. This study used different pancreatic cancer cell lines and in different animal models to confirm the relationship between simvastatin and pancreatic cancer. Flow cytometry and luciferase-based bioluminescent images were used to investigate the cell cycle and tumor growth changes under simvastatin treatment. Simvastatin decreased the MIA PaCa-2 cells, PANC-1 cells, and BxPC-3 cell viability significantly and may arrest the cell cycle in the G0 phase. During in vivo study, subcutaneously implanted simvastatin pre-treated pancreatic cancer cells and intraperitoneally treated simvastatin continuously demonstrated a slower tumor growth rate and decreased the tumor/body weight ratio significantly. In intravenous implant models, implanted simvastatin-pre-treated BxPC-3 cells and cells treated along with simvastatin significantly decreased the tumor growth curve. Implanting the simvastatin-pre-treated pancreatic cells in the subcutaneous model showed better growth inhibition than the intravenous model. These results suggest simvastatin treatment may relate to different signaling pathways in local growth and metastasis. Pancreatic cancer cells presented different growth patterns in different animal-induced models, which could be important for clinical reference when it comes to the relationship of long-term statin use and pancreatic cancer.

The preventability of trauma-related death: A two-year cohort study in a trauma center in middle Taiwan.

INTRODUCTION: The preventable death rate (PDR) is an important parameter in the quality assurance of traumatic care. Medical errors or untimely management may occur during stressful trauma care, resulting in preventable deaths. We aimed to develop an applicable PDR model in a trauma center in middle Taiwan. MATERIALS AND METHODS: We identified adult trauma-related deaths which occurred from January 1, 2018 to December 31, 2019 at our hospital. Patients with a trauma and injury severity score (TRISS) <75% or ≥75% but with a chance of preventability, as determined by a trauma surgeon, were discussed by a panel comprising an emergency physician and surgeons specializing in different fields of medicine. Deaths were subsequently classified as definitely preventable (DP), potentially preventable (PP), or non-preventable (NP). Causes of DP or PP deaths were categorized as delayed diagnosis, delayed treatment, technical error, or inadequate infection prevention/control. The relationship between the time and cause of preventable deaths was also analyzed. RESULTS: This study included 127 trauma-related deaths, of which 39 were discussed by the panel. Eight patients (6.3%) were categorized as DP, eight (6.3%) as PP, and 111 (87.4%) as NP. Among patients with preventable deaths, inadequate infection prevention/control, delayed treatment, delayed diagnosis, and technical error were identified in six (37.5%), five (31.2%), three (18.8%), and two (12.5%) patients, respectively. Four patients in the inadequate infection prevention/control group (4/6, 66.7%) died of aspiration pneumonia during the recovery phase. CONCLUSION: A PDR evaluation model was developed and revealed that postoperative care is as important as a timely diagnosis and treatment to avoid preventable deaths following trauma.

Prognostic significance of dynamin-related protein 1 expression in advanced lung adenocarcinoma.

BACKGROUND: Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission and is activated by phosphorylation at serine 616. We previously demonstrated that DRP1 activation is regulated by epidermal growth factor receptor (EGFR) signaling and multiple kinases in lung adenocarcinoma, and is significantly associated with an increased risk of postoperative recurrence in early stage lung adenocarcinoma. However, it is unclear whether DRP1 activation is associated with worse prognosis in patients with advanced lung adenocarcinoma. This study is aimed to examine whether P(S616)-DRP1 expression is significantly related to the survival of patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: Biopsy samples were obtained from patients with stage IV lung adenocarcinoma. The activation status of DRP1 in cancer cells was quantified based on the immunohistochemical stain of phosphorylated DRP1 at serine 616 [P(S616)-DRP1]. Results of EGFR, ALK, ROS1, and KRAS mutations were retrieved from the medical records. The staining intensity and the histological scores (H-scores) of P(S616)-DRP1 were analyzed for association with progression-free survival (PFS) under first-line tyrosine-kinase inhibitors (TKIs) and with overall survival (OS). RESULTS: Overall, 123 patients with stage IV lung adenocarcinoma constituted the study population, and 90 (73.2%) patients received TKIs as the first-line treatments. The median P(S616)-DRP1H-score was used to dichotomize the study population into the high (n = 61) and low (n = 62) DRP1 activation groups. DRP1 was significantly less phosphorylated in lung adenocarcinoma with EGFR, ALK, ROS1, and KRAS mutations. Importantly, in patients who received first-line TKIs, DRP1 phosphorylation was not significantly correlated with PFS and OS. Multivariate Cox proportional hazard models showed that high DRP1 activation in cancer cells was not significantly associated with worse OS in the study population (adjusted hazard ratio: 1.402, 95% confidence interval: 0.865-2.271, p = 0.170). Similar results were obtained in the analysis based on the intensities of P(S616)-DRP1 in cancer cells. CONCLUSIONS: Our data demonstrate that DRP1 phosphorylation is not related to the prognosis of patients with advanced lung adenocarcinoma.

Multi-kinase framework promotes proliferation and invasion of lung adenocarcinoma through activation of dynamin-related protein 1.

Recent studies revealed the role of dynamin-related protein 1 (DRP1), encoded by the DNM1L gene, in regulating the growth of cancer cells of various origins. However, the regulation, function, and clinical significance of DRP1 remain undetermined in lung adenocarcinoma. Our study shows that the expression and activation of DRP1 are significantly correlated with proliferation and disease extent, as well as an increased risk of postoperative recurrence in stage I to stage IIIA lung adenocarcinoma. Loss of DRP1 in lung adenocarcinoma cell lines leads to an altered mitochondrial morphology, fewer copies of mitochondrial DNA, decreased respiratory complexes, and impaired oxidative phosphorylation. Additionally, the proliferation and invasion are both suppressed in DRP1-depleted lung adenocarcinoma cell lines. Our data further revealed that DRP1 activation through serine 616 phosphorylation is regulated by ERK/AKT and CDK2 in lung adenocarcinoma cell lines. Collectively, we propose the multikinase framework in activating DRP1 in lung adenocarcinoma to promote the malignant properties. Biomarkers related to mitochondrial reprogramming, such as DRP1, can be used to evaluate the risk of postoperative recurrence in early-stage lung adenocarcinoma.

Mitofusins regulate lipid metabolism to mediate the development of lung fibrosis.

Accumulating evidence illustrates a fundamental role for mitochondria in lung alveolar type 2 epithelial cell (AEC2) dysfunction in the pathogenesis of idiopathic pulmonary fibrosis. However, the role of mitochondrial fusion in AEC2 function and lung fibrosis development remains unknown. Here we report that the absence of the mitochondrial fusion proteins mitofusin1 (MFN1) and mitofusin2 (MFN2) in murine AEC2 cells leads to morbidity and mortality associated with spontaneous lung fibrosis. We uncover a crucial role for MFN1 and MFN2 in the production of surfactant lipids with MFN1 and MFN2 regulating the synthesis of phospholipids and cholesterol in AEC2 cells. Loss of MFN1, MFN2 or inhibiting lipid synthesis via fatty acid synthase deficiency in AEC2 cells exacerbates bleomycin-induced lung fibrosis. We propose a tenet that mitochondrial fusion and lipid metabolism are tightly linked to regulate AEC2 cell injury and subsequent fibrotic remodeling in the lung.

Hydrocarbon pneumonitis following fuel siphonage: A case report and literature review.

BACKGROUND: People sometimes siphon fuel to fill their tanks. However, this is a potentially dangerous procedure and may cause hydrocarbon pneumonitis. We present the case of a patient with severe hydrocarbon pneumonitis after siphoning fuel. The patient underwent artificial ventilation and was admitted to hospital for 97 days. METHODS: We review the relevant literature for a better understanding of clinical features and management strategies for hydrocarbon pneumonitis following fuel siphonage. RESULTS: We reviewed 15 articles, which included 3 original articles and 12 case reports that reported the clinical features of fuel siphonage. In addition, we added our presented case for data analysis. A total of 40 cases were included in this review. The literature review found that hydrocarbon pneumonitis caused by fuel siphonage occurs worldwide and that most patients (80%) became symptomatic within 1 day of aspiration. Cough (70%), chest pain (62.5%), dyspnoea (55%), and fever (52.5%) presented in more than half of all patients. The right middle lobe (80%) was the predominantly involved lung field; more than one-third of patients (36.7%) showed the involvement of two lobes. CONCLUSION: Patient history, computed tomographic scans of the chest, and bronchoalveolar lavage are the commonly used diagnostic tools. Supportive care remains the foundation of treatment, whereas antibiotics, steroids, and bronchoalveolar lavage are practical therapies. Patients' clinical improvement precedes the resolution of lesions on chest X-ray. Most complications arise from pulmonary lesions. The prognosis of patients suffering from hydrocarbon pneumonitis following fuel siphonage might be improved by accurate diagnosis and appropriate care.

Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study.

OBJECTIVES: Recent metabolomic studies of sepsis showed that increased circulatory acylcarnitines were associated with worse survival. However, it is unknown whether plasma carnitine and acylcarnitines can reflect the severity of sepsis, and the role of specific acylcarnitines in prognostic assessment need further confirmation. This study aimed to clarify these questions. DESIGN: Prospective multicenter cohort studies with derivation and validation cohort design. SETTING: ICUs at two medical centers and three regional hospitals in Taiwan. PATIENTS: Patients with sepsis and acute organ dysfunction were enrolled. Recruitment of the derivation (n = 90) and validation cohorts (n = 120) occurred from October 2010 through March 2012 and January 2013 through November 2014, respectively. INTERVENTIONS: Plasma samples were collected immediately after admission, and the levels of carnitine and acylcarnitines were measured by ultra-high performance liquid chromatography-mass spectrometry. MEASUREMENTS AND MAIN RESULTS: In the derivation cohort, increased plasma levels of short- and medium-chain acylcarnitines were significantly associated with hepatobiliary dysfunction, renal dysfunction, thrombocytopenia, and hyperlactatemia. However, acetylcarnitine is the only acylcarnitine significantly correlating with various plasma cytokine concentrations and also associated with blood culture positivity and 28-day mortality risk. The association between plasma acetylcarnitine and multiple organ dysfunction severity, blood culture positivity, and 28-day mortality, was confirmed in the validation cohort. Patients with high plasma acetylcarnitine (≥ 6,000 ng/mL) had significantly increased 28-day mortality compared with those with plasma acetylcarnitine less than 6,000 ng/mL (52.6% vs 13.9%; hazard ratio, 5.293; 95% CI, 2.340-11.975; p < 0.001 by Cox proportional hazard model). CONCLUSIONS: We confirm that plasma acetylcarnitine can reflect the severity of organ dysfunction, inflammation, and infection in sepsis and can serve as a prognostic biomarker for mortality prediction.

The Effectiveness of Home Services in Taiwan: A People-Centered Approach.

Among available home and community-based services in Taiwan, there should be a focus on providing people with people-centered, value-based services. This study aims to follow up the people-centered health outcomes of care recipients and to examine the factors associated with to feedback for policy and practice in long-term care. A total of 9889 persons from the long-term care dataset were followed up for two years (T0⁻T4). The Cox Proportional Hazard Regression analyses to analyze mortality and the mixed effect models for health outcomes were used. Three classes among the care recipients were identified. Health profiles (HR = 1.46 and 2.56 for FI and FD compared with RI, p < 0.001), subsidy gap (HR = 1.01), and living status (HR = 0.88 for those living with spouse only) had a significant impact on mortality. The overall dropout rate was 52.3% at two years, and the health profiles at baseline significantly influenced the health outcome's change. The health heterogeneity matters and influences subsequent outcomes. To reach the goal of the HCBS, regular and exact monitoring of care recipients is crucial, while feedback regarding health outcomes and a greater focus on providing person-centered and responsive services in the community are also required.

Assessment of the clinical efficacy of the heart spectrum blood pressure monitor for diagnosis of atrial fibrillation: An unblinded clinical trial.

Atrial fibrillation (AF) is the most common arrhythmia. The most common diagnostic method, 12-lead electrocardiogram (ECG), can record episodes of arrhythmia from which the type and severity can be determined. The Heart Spectrum Blood Pressure Monitor (P2; OSTAR Meditech Corp., New Taipei City, Taiwan) is used to measure cardiovascular pressure change with fast Fourier transform (FFT) analysis to obtain heart rate frequency variability and accurate blood pressure data. We compared the diagnostic efficacy of the Heart Spectrum Blood Pressure Monitor to a 12-lead ECG (gold standard) for patients with AF. Three measurement methods were used in this study to analyze the heart index and compare the results with simultaneous 12-lead ECG: blood pressure; mean arterial pressure, which was calculated from individual blood pressure as a constant pressure; and a constant pressure of 60 mmHg. The physician used a 12-lead ECG and the Heart Spectrum Blood Pressure Monitor simultaneously. The Heart Spectrum Blood Pressure Monitor used FFT analysis to diagnose AF, and the findings were compared to the 12-lead ECG readings. This unblinded clinical trial was conducted in the emergency department of Taipei Medical University Hospital. Twenty-nine subjects with AF and 33 without AF aged 25 to 97 y (mean, 63.5 y) were included. Subjects who were exposed to high-frequency surgical equipment during testing, those with cardiac pacemakers or implantable defibrillators, and pregnant women were excluded. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 97%, 97%, 97%, and 97%, respectively, for method 1; 90%, 100%, 100%, and 91%, respectively, for method 2; and 100%, 94%, 94%, and 100%, respectively, for method 3. The sensitivity, specificity, PPV, and NPV for both methods ranged between 90% and 100%, indicating that the Heart Spectrum Blood Pressure Monitor can be effectively applied for AF detection.

A Comparative Study of Medical Device Regulations:: US, Europe, Canada, and Taiwan.

The medical device industry is an industry dealing with multiple types of products covering a wide range of applications. As the safety and effectiveness of medical devices are vital to human health, the products must be managed by strict regulations according to the different risk levels. A total product life cycle regulatory system including product design, manufacture, premarket gate keeping, and postmarket monitoring is a common framework for medical device regulations. However, the variety and innovativeness of medical devices are challenging the current regulatory frameworks. Hence, the competent authorities responsible for medical devices worldwide keep renewing their regulatory systems to ensure the safety and effectiveness of medical devices. This review aims to provide an informative review of the regulatory frameworks of medical devices in the United States, Europe, Canada, and Taiwan, with a particular focus on updated regulatory changes in these countries and the current status of global harmonization on medical devices.

Severe lymphopenia is associated with elevated plasma interleukin-15 levels and increased mortality during severe sepsis.

Sepsis-related mortality has been found increased in RAG-1 knockout mice. However, in patients admitted to medical intensive care units, it is unknown whether severe lymphocyte depletion at admission is associated with increased interleukin (IL)-7 and IL-15 levels in circulation, and increased mortality. We prospectively enrolled 92 patients who were admitted to medical intensive care units for severe sepsis or septic shock. At admission, 24 patients (26.1%) had severe lymphopenia, defined as lymphocyte counts of less than 0.5 × 10(3)/µL. Severe lymphopenia was associated with significantly higher plasma levels of tumor necrosis factor α, IL-6, IL-8, and IL-10 and was also independently associated with 28-day mortality (adjusted hazard ratio, 3.532; 95% confidence interval, 1.482-8.416; P = 0.004). The levels of plasma IL-15, but not IL-7, were increased modestly in patients with severe lymphopenia compared with those without (median, 12.2 vs. 6.4 pg/mL; P = 0.005). The elevated plasma IL-15 levels were contrarily associated with significantly decreased B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells. In conclusion, severe lymphopenia was associated with increased mortality in patients with severe sepsis. We found that patients with sepsis with severe lymphopenia had down-regulated B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells, despite increased plasma IL-15 concentrations. Whether IL-7 and IL-15 are insufficient in patients with severe lymphopenia during severe sepsis warrants further investigations.

Effects of pre-arrest comorbidities on 90-day survival of patients resuscitated from out-of-hospital cardiac arrest.

BACKGROUND: Factors that affect prognosis in successfully resuscitated out-of-hospital cardiopulmonary arrest (OHCA) patients in the intensive care unit (ICU) who survived the initial 24 h period of post-resuscitation have not been established. This study was conducted to evaluate the clinical prognostic factors associated with 90-day survival in patients who were successfully resuscitated from OHCA. METHODS: This study was conducted at a tertiary large university hospital. Clinical data were obtained from the medical records of 224 adult non-traumatic patients who were successfully resuscitated from OHCA and who survived the initial 24 h post-resuscitation phase. Univariate and multivariate analyses were performed to identify independent predictors associated with 90-day survival. RESULTS: Significant adverse prognosticators included liver cirrhosis (HR 4.36, 95% CI 1.76 to 10.79), prolonged cardiopulmonary resuscitation (CPR) duration >20 min (HR 1.95, 95% CI 1.27 to 3.00) and underlying malignancy (HR 1.64, 95% CI 1.06 to 2.54). Favourable prognostic factors included the best Glasgow Coma Scale within 24-48 h after return of spontaneous circulation >5 (HR 0.16, 95% CI 0.04 to 0.68), mean arterial pressure on ICU admission >100 mmHg (HR 0.81, 95% CI 0.43 to 0.94) and the presenting rhythm of pulseless electrical activity (HR 0.44, 95% CI 0.1 to 0.63). A high burden of comorbidities (by Charlson score >5) was associated with significantly poorer 90-day survival (HR 1.60, 95% CI 1.03 to 2.49). CONCLUSIONS: Underlying comorbidities have a significant influence on survival. CPR duration, post-resuscitative blood pressure and early neurological recovery may serve as practical clinical predictors of short-term survival.