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The prescribing patterns and effectiveness of sedatives and analgesics for severe traumatic brain injury patients in Taiwan
No full text[[abstract]]BACKGROUND: Traumatic brain injury (TBI) is a major global health challenge associated with high mortality and morbidity. Secondary brain injury caused by disrupted intracranial pressure (ICP) regulation often necessitates sedation; however, guidelines lack specificity for TBI management. METHODS: This study analyzed sedation and analgesia prescribing patterns and their outcomes in severe TBI patients in Taiwan using National Health Insurance Research Database data (2012-2019). Severe TBI patients intubated during intensive care unit (ICU) hospitalization were included. The primary outcome was 30-day all-cause mortality, with sensitivity analyses for 14-day mortality and 30-day all-cause mortality excluding deaths within 3 days. Inverse probability of treatment weighting (IPTW) was applied to balance patient characteristics across groups. Mortality rates across groups were evaluated using Kaplan-Meier survival analysis. At the same time, the Cox proportional hazards model simultaneously assessed the impact of various risk factors, such as age and comorbidities, on mortality. RESULTS: Among 6030 patients, sedation and analgesia patterns varied, with midazolam combined with opioids being the most common regimen. Compared to the reference group (sedatives with opioids), the risk of death was highest in the no-prescription group (HR = 2.73, 95 % CI = 2.60-2.86), followed by the sedation-only group (HR = 1.58, 95 % CI = 1.50-1.66) and the opioids-only group (HR = 1.49, 95 % CI = 1.42-1.57; all p < 0.0001). Sensitivity analyses confirmed consistent trends. CONCLUSIONS: These findings underscore the importance of optimizing sedation practices and enhancing awareness to improve outcomes for severe TBI patients
Effectiveness of full mRNA vaccinations to prevent COVID-19 among immunocompromised patients receiving tixagevimab-cilgavimab as pre-exposure prophylaxis
No full text[[abstract]]Pre-exposure prophylaxis with monoclonal antibodies (mAbs) offers protection against COVID-19 in immunocompromised patients. To attest full vaccinations, defined by ≥ 3-dose mRNA vaccines, providing additional protection effect on mAbs against COVID-19, we retrospectively compared the breakthrough SARS-CoV-2 infection rates between adult immunocompromised patients with and without full vaccinations before receiving prophylactic tixagevimab-cilgavimab during the Omicron BA.5 dominant period. Among 148 patients, most (96.6 %) had hematologic malignancies. Fifty-nine (39.9 %) patients received full vaccinations before tixagevimab-cilgavimab. Overall, 19 (12.8 %) patients have breakthrough infections, and only three of them had full vaccinations. By a multivariable logistic regression model, receipt of full vaccinations was the only independent factor associated with prevention of breakthrough infections (adjusted odds ratio, 0.26 [95 % CI, 0.07–0.95]). The Kaplan–Meier estimate showed a lesser trend of breakthrough infections with those receiving full vaccinations (P = 0.08). Our study underscores the importance of full vaccinations among immunocompromised patients receiving pre-exposure prophylactic mAbs against COVID-19
The COVID-19 pandemic and internet searches for divorce with stay-at-home behavior as a mediator: A multinational longitudinal study
No full text[[abstract]]This study integrates an analysis of Google Trends data on divorce search volumes, Google Location History to assess stay-at-home behavior, and COVID-19 death rates from March 2020 to October 2022 across 45 countries. Using causal mediation analysis, we examined the mediating role of stay-at-home behavior on the impact of pandemic severity on divorce-related searches. Findings indicate a significant relationship between COVID-19 death rates and reduced divorce searches during the first two years, with no mediation by stay-at-home behavior. In the third year, stay-at-home behavior began significantly mediating an increase in divorce searches, especially pronounced in high-income countries. These results highlight the evolving societal responses to the pandemic and underscore the importance of adaptable support strategies in the face of changing marital dynamics during public health crises
Wireless in situ catalytic electron signaling-mediated transcriptomic reprogramming for neuron regeneration via adaptable antennas
No full text[[abstract]]Electron signaling and oxygen level are vital for regulating neural-cell fate and brain recovery. However, clinical challenges arise from the short half-life and the difficulty of spatiotemporally controlled oxygen release and electric signals. In this study, a wireless-charging sustained oxygen release from conductive microgels (SOCO) served as an antenna and an on-demand O-2 release for nerve regeneration is developed. Introducing "electromagnetic messenger", using external alternating magnetic field (AMF) to enhance catalytic oxygen release and electrical stimulation to promote the reconstruction of blood vessels and neurons in vivo. SOCO also reduces TBI glial scarring by reducing activated microglia and stellate cells, promoting infiltration of new neurons. In whole-brain analyses, effective somatostatin (Sst) production inhibits gamma-aminobutyric acid (GABA) synthesis in injured areas, thereby improving brain function and behavioral recovery. Furthermore, spatial multiomics combined with single-cell deconvolution analysis reveals the treatment reprogramming in vivo brain transcriptome of angiogenic markers (Il1a, Lgals3) and GABAergic pathway via modulation of GAD65/67 activity, guiding angiogenesis and neuronal regeneration. This in situ catalytic SOCO with noncontact AMF presents an "electromagnetic messenger"-based therapeutics for reprogramming the neuro-regeneration and brain function recovery in TBI
Sex- and stage-specific predictors of anemia in chronic kidney disease: A retrospective cohort study
No full text[[abstract]]Background: Anemia is a common complication of chronic kidney disease (CKD), yet no study has explored differences in anemia risk factors based on disease severity and gender. Therefore, this study investigates potential differences in anemia risk among individuals with varied kidney disease severities and sexes. Methods: This multicenter, longitudinal cohort study was conducted using data (2008-2016) from the Epidemiology and Risk Factors Surveillance of CKD database. This database was associated with Taiwan's National Health Insurance Research Database (for the 2008-2019 period). To identify predictive risk factors for anemia, we developed a subset multivariate logistic model using stepwise variable selection. Additionally, 10-fold cross-validation was conducted to facilitate model selection and internal validation. Results: Of the 5656 patients with CKD, 519 (9.18%) with anemia and 5137 (90.82%) without. After adjusting for age, sex, and serum creatinine, stepwise logistic regression analysis identified the main independent predictive factors for anemia in CKD patients. Notably, "Receive low sodium diet education" (OR: 0.66, 95% CI: 0.446-0.975), "DBP (mmHg)" (OR: 0.98, 95% CI: 0.965-0.999), "Gout" (OR: 1.86, 95% CI: 1.175-2.937), and "Congestive heart failure" (OR: 1.85, 95% CI: 1.131-3.028) was significantly associated with the presence of anemia among CKD patients. Conclusions: This study identifies gout and cardiovascular disease as important correlates of anemia in patients with CKD. Moreover, it reveals an inverse association between elevated diastolic blood pressure and receiving education on a low-sodium diet with the occurrence of anemia
Referral criteria for specialist palliative care for patients with dementia
No full text[[abstract]]Importance Patients with dementia have considerable supportive care needs. Specialist palliative care may be beneficial, but it is unclear which patients are most appropriate for referral and when they should be referred. Objective To identify a set of consensus referral criteria for specialist palliative care for patients with dementia. Design, Setting, and Participants In this survey study using 3 rounds of Delphi surveys, an international, multidisciplinary panel of clinicians from 5 continents with expertise in the integration of dementia and palliative care were asked to rate 83 putative referral criteria (generated from a previous systematic review and steering committee discussion). Specialist palliative care was defined as an interdisciplinary team consisting of practitioners with advanced knowledge and skills in palliative medicine offering consultative services for specialist-level palliative care in (nonhospice) inpatient, outpatient, community, and home-based settings. Main Outcomes and Measures Consensus was defined a priori as at least 70% agreement among experts. A criterion was coded as major if the experts advocated that meeting 1 criterion alone was satisfactory to justify a referral. Data were summarized using descriptive statistics. Results Of the 63 invited and eligible panelists, the response rate was 58 (92.1%) in round 1, 58 (92.1%) in round 2, and 60 (95.2%) in round 3. Of the 58 panelists who provided demographic data in round 1, most were aged 40 to 49 years (28 of 58 [48.3%]), and 29 panelists (50%) each were men and women. Panelists achieved consensus on 15 major and 42 minor criteria for specialist palliative care referral. The 15 major criteria were grouped under 5 categories, including dementia type (eg, rapidly progressive dementia), symptom distress (eg, severe physical symptoms), psychosocial factors or decision-making (eg, request for hastened death, assisted suicide, or euthanasia), comorbidities or complications (eg, >= 2 episodes of aspiration pneumonia in the past 12 months); and hospital use (eg, >= 2 hospitalizations within the past 3 months). Conclusions and Relevance In this Delphi survey study, international experts reached consensus on a range of criteria for referral to specialist palliative care. With testing and validation, these criteria may be used to standardize specialist palliative care access for patients with dementia across various care settings
Blood pressure variability and risk of cardiovascular events and mortality in real-world clinical settings
No full text[[abstract]]BACKGROUND: The real-world applicability of long-term blood pressure (BP) variability measurements remains underexplored. We evaluated the association between visit-to-visit BP variability and the risk of cardiovascular events and all-cause mortality using electronic health records. METHODS: In this retrospective cohort study at a large academic medical center in Taiwan, we calculated the variability independent of the mean (VIM) and average real variability of BP using electronic health records of 16 945 adults with at least one outpatient BP measurement in any 3 consecutive years from 2012 to 2017. We used Cox proportional hazards models to assess associations between BP variability and cardiovascular events, including cardiovascular deaths, and all-cause mortality through 2020. RESULTS: Over a median follow-up of 4 years, 317 patients experienced cardiovascular events, and 582 died. Adjusted hazard ratios (HRs) for cardiovascular events increased gradually across both VIM and average real variability quartiles of BP. The adjusted HRs (95% CIs) per interquartile range increase in systolic BP variability was 1.24 (1.09-1.41) for VIM and 1.11 (1.01-1.23) for average real variability. For diastolic BP, the HRs (95% CIs) were 1.22 (1.09-1.36) and 1.13 (1.02-1.24), respectively. Similar results were observed for all-cause mortality except a weaker association with average real variability of diastolic BP (HR, 1.08 [95% CI, 0.99-1.17]). The association between VIM of BP and risk of cardiovascular events was consistent across patient subgroups. CONCLUSIONS: In the electronic health records analysis, visit-to-visit BP variability was independently associated with the risk of cardiovascular events and all-cause mortality. Our findings indicate the applicability of BP variability indices in real-world health care settings
Eggerthella lenta down regulated flavone and flavonol biosynthesis promoted Kawasaki disease
No full text[[abstract]]Kawasaki Disease (KD) is a multisystemic vasculitis of unknown aetiology in children. The incidence of KD varies by geographic area and correlates with differences in gut microbiota patterns, with the highest incidence in Asian. This study aimed to investigate alterations in faecal microbiota and assess their relationship with systemic inflammation in KD patients. A total of 59 patients and 55 matched controls were included. Fecal samples were collected at the onset of KD. The V3/V4 regions of 16S rDNA were sequenced using the MiSeq platform. PICRUSt 2 was used to analyse the potential functional pathways involved in gut dysbiosis. Alpha (p < 0.042) and beta (p < 0.001) diversity in KD were significantly decreased when compared to the control group. After multivariate regression, among the seven critical microbes, increased Eggerthella lenta (p = 0.016) and decreased Bacteroides ovatus (p = 0.014) could also predict KD risk using receiver operating characteristic curve (ROC) analysis (Eggerthella lenta: area under the ROC curve, AUC = 0.841, odds ratio = 23.956; Bacteroides ovatus: AUC = 0.816, odds ratio = 31.365). Notably, Bacteroides ovatus was positively correlated with blood segment cells (p = 0.006), but negatively correlated with blood lymphocytes (p = 0.013). After multivariate regression, flavone and flavonol biosynthesis decreased in children with KD (p < 0.001). Our results indicated that both Bacteroides ovatus and Eggerthella lenta may deregulate flavone and flavonol biosynthesis, consequently modulating immune cells and potentially triggering KD. This study suggests that alterations in the gut microbiota are closely associated with immune responses and provides a new perspective on the aetiology, pathogenesis, and treatment of KD
Engineered nanoparticle transformations: Rethinking toxicity in water
No full text[[abstract]]The burgeoning production and utilization of engineered nanoparticles (ENPs) in recent years has precipitated the intentional and inadvertent discharge of ENPs into the environment, where undergo different transformations. Extensive research has investigated the mechanisms underlying the environmental transformations of metal-based ENPs, with a focus on alterations in the properties of their transformation products. It is widely recognized that ENP-biota interactions are influenced by various ENP characteristics, such as size, shape, surface area, chemical composition, surface charge, and chemistry. As a result of transformations, changes in ENP properties are anticipated to affect biotic interactions, including cellular recognition and trafficking, thus impacting organismal responses. This hypothesis has only recently been subjected to experimental scrutiny, mainly within simplified ENP-organism systems. Major studies indicate that the acute toxicity of transformed ENPs is largely driven by the rate and yield of metal ion release, similar to pristine ENPs. However, when transformations reduce ENP dissolution, they may enhance environmental persistence, rendering other toxicity mechanisms more significant. We meticulously examine available data on the toxicity of various transformed ENPs, aiming to systematically assess the actual responses of aquatic biota concerning altered ENP properties and differing environmental factors. In this context, we highlight scenarios involving multiple ENP transformations and specific local environmental modifications. These research directions warrant further exploration, especially under real-world conditions. Such efforts will expand the database, which, through the application of modern machine learning and artificial intelligence tools, can aid in predicting the fate of ENPs released from the increasing array of nano-products
A phase I study of liposomal Irinotecan (ONIVYDE®) in combination with TAS-102 (LONSURF®) in refractory solid tumors
No full text[[abstract]]Onivyde, a liposome-encapsulated irinotecan, is used for advanced pancreatic, while TAS-102 (trifluridine/tipiracil) is indicated for metastatic colorectal and gastric cancers. This study aims to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), and safety profiles of liposomal irinotecan combined with TAS-102. This multicenter, phase I study utilized a 3 + 3 dose-escalation design. Patients with treatment-refractory solid malignancies received free base liposomal irinotecan at 50-70 mg/m2 on Day 1 and TAS-102 at 25-35 mg/m2 twice daily on Days 1-5 of a 14-day cycle. Patients homozygous for UGT1A1*28 (TA7/TA7), UGT1A1*6 (A/A), or double heterozygous (TA6/TA7 and G/A) alleles were excluded. Prophylactic G-CSF was allowed. Twenty-six evaluable patients were enrolled across seven dose levels of liposomal irinotecan (free-base)/TAS-102 combination: 3 patients each at level 1 (50/25 mg/m2), level 2A (60/25 mg/m2), level 2B (50/30 mg/m2), and level 3 (60/30 mg/m2); 6 at level 4A (70/30 mg/m2); 3 at level 4B (60/35 mg/m2); and 5 at level 5 (70/35 mg/m2). An additional 15 patients were enrolled in the expansion cohort at the MTD of 70/30 mg/m2 (level 4A), designated as the RP2D. Overall grade 3-4 treatment-related adverse events occurred in 44.2% of 43 all treated patients, with neutropenia (16.3%), diarrhea (14%), and fatigue (11.6%). Partial responses were observed in 18.4% of patients, predominantly in neuroendocrine tumor, gastric and esophageal carcinomas. The combination of liposomal irinotecan and TAS-102 at the RP2D of 70/30 mg/m2 demonstrated acceptable safety and promising efficacy in refractory solid tumors, warranting further investigation