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1.
BMC Med Res Methodol ; 21(1): 23, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541273

RESUMO

BACKGROUND: The U.S. lacks a stroke surveillance system. This study develops a method to transform an existing registry into a nationally representative database to evaluate acute ischemic stroke care quality. METHODS: Two statistical approaches are used to develop post-stratification weights for the Get With The Guidelines-Stroke registry by anchoring population estimates to the National Inpatient Sample. Post-stratification survey weights are estimated using a raking procedure and Bayesian interpolation methods. Weighting methods are adjusted to limit the dispersion of weights and make reasonable epidemiologic estimates of patient characteristics, quality of hospital care, and clinical outcomes. Standardized differences in national estimates are reported between the two post-stratification methods for anchored and non-anchored patient characteristics to evaluate estimation quality. Primary measures evaluated are patient and hospital characteristics, stroke severity, vital and laboratory measures, disposition, and clinical outcomes at discharge. RESULTS: A total of 1,388,296 acute ischemic strokes occurred between 2012 and 2014. Raking and Bayesian estimates of clinical data not available in administrative data are estimated within 5 to 10% of margin for expected values. Median weight for the raking method is 1.386 and the weights at the 99th percentile is 6.881 with a maximum weight of 30.775. Median Bayesian weight is 1.329 and the 99th percentile weights is 11.201 with a maximum weight of 515.689. CONCLUSIONS: Leveraging existing databases with patient registries to develop post-stratification weights is a reliable approach to estimate acute ischemic stroke epidemiology and monitoring for stroke quality of care nationally. These methods may be applied to other diseases or settings to better monitor population health.

2.
JAMA Netw Open ; 4(2): e2037438, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33591368

RESUMO

Importance: Although the use of factor Xa (FXa) inhibitors has increased substantially over the past decade, there are limited data on characteristics and outcomes of FXa inhibitor-associated intracerebral hemorrhage (ICH). Objective: To investigate the association between prior oral anticoagulant use (FXa inhibitors, warfarin, or none) and in-hospital outcomes among patients with nontraumatic ICH. Design, Setting, and Participants: This is a cohort study of 219 701 patients with nontraumatic ICH admitted to 1870 hospitals in the Get With The Guidelines-Stroke registry between October 2013 and May 2018. Data analysis was performed in December 2019. Exposures: Anticoagulation therapy before ICH. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes were a composite measure of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge. Results: Of 219 701 patients (mean [SD] age, 68.2 [15.3] years; 104 940 women [47.8%]), 9202 (4.2%) were taking FXa inhibitors, 21 430 (9.8%) were taking warfarin, and 189 069 (86.0%) were not taking any oral anticoagulant before ICH. Patients taking FXa inhibitors or warfarin were older and had higher prevalence of cardiovascular risk factors. Compared with those not taking an oral anticoagulant (42 660 of 189 069 patients [22.6%]), the in-hospital mortality risk was higher for both FXa inhibitors (2487 of 9202 patients [27.0%]; adjusted odds ratio [aOR], 1.27; 95% CI, 1.20-1.34; P < .001) and warfarin (7032 of 21 430 patients [32.8%]; aOR, 1.67; 95% CI, 1.60-1.74; P < .001). Both FXa inhibitors (3478 of 9202 patients [37.8%]; aOR, 1.19; 95% CI, 1.13-1.26; P < .001) and warfarin (9151 of 21 430 patients [42.7%]; aOR, 1.50; 95% CI, 1.44-1.56; P < .001) were associated with higher odds of death or discharge to hospice compared with not taking oral anticoagulation (58 022 of 189 069 patients [30.7%]). Although the rates of discharge home, independent ambulation, mRS scores of 0 or 1, and mRS scores of 0 to 2 were numerically lower among patients taking FXa inhibitors, these differences were not significant compared with patients not taking oral anticoagulants. In contrast, patients taking FXa inhibitors were less likely to die (aOR, 0.76; 95% CI, 0.72-0.81; P < .001) or to experience death or discharge to hospice (aOR, 0.79; 95% CI, 0.75-0.84; P < .001), more likely to be discharged home (aOR, 1.18; 95% CI, 1.10-1.26; P < .001), and had better mRS scores at discharge (eg, mRS scores of 0-1: aOR, 1.24; 95% CI, 1.09-1.40; P < .001) than those treated with warfarin. Concomitant warfarin and antiplatelet therapy (either single or dual) was associated with worse outcomes compared with taking warfarin alone (eg, in-hospital mortality for dual-antiplatelet agents: aOR, 2.07; 95% CI, 1.72-2.50; P < .001). However, such incremental risk was not significant in patients taking FXa inhibitors. Conclusions and Relevance: In this cohort study, FXa inhibitor-associated ICH was associated with higher risk of mortality or death or discharge to hospice than not taking an oral anticoagulant, but patients taking FXa inhibitors had better outcomes than those with warfarin-related ICH.

3.
Stroke Vasc Neurol ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526632

RESUMO

BACKGROUND AND PURPOSE: Depression is common after stroke and is often treated with antidepressant medications (AD). ADs have also been hypothesised to improve stroke recovery, although recent randomised trials were neutral. We investigated the patterns of in-hospital AD initiation after ischaemic stroke and association with clinical and readmission outcomes. METHODS: All Medicare fee-for-service beneficiaries aged 65 or older hospitalised for ischaemic stroke in participating Get With The Guidelines-Stroke hospitals between April and December 2014 were eligible for this analysis. Outcome measures included days alive and not in a healthcare institution (home time), all-cause mortality and readmission within 1-year postdischarge. Propensity score (PS)-adjusted logistic regression models were used to evaluate the associations between AD use and each outcome measure. We also compared outcomes in patients prescribed selective serotonin reuptake inhibitors (SSRIs) AD versus those prescribed non-SSRI ADs. RESULTS: Of 21 805 AD naïve patients included in this analysis, 1835 (8.4%) were started on an AD at discharge. Patients started on an AD had higher rates of depression and prior ischaemic stroke, presented with higher admission National Institutes of Health Stroke Scale score and were less likely to be discharged home. Similarly, patients started on an SSRI had lower rates of discharge to home. Adjusting for stroke severity, patients started on an AD had worse all-cause mortality, all-cause readmission, major adverse cardiac events, readmission for depression and decreased home-time. However, AD use was also associated with an increased risk for the sepsis, a falsification endpoint, suggesting the presence of residual confounding. CONCLUSIONS: Patients with ischaemic stroke initiated on AD therapy are at increased risk of poor clinical outcomes and readmission even after PS adjustment, suggesting that poststroke depression requiring medication is a poor prognostic sign. Further research is needed to explore the reasons why depression is associated with worse outcome, and whether AD treatment modifies this risk or not.

4.
Pain ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33433144

RESUMO

ABSTRACT: Adults are more likely to suffer from chronic pain than minors, and its underlying mechanism remains unclear. SIRT1 as important aging-related protein with function of lifespan extension, whether SIRT1 plays a role in the different pain vulnerability of adult and juvenile remains unclear. Here, we found that the expression level of SIRT1 in dorsal root ganglia (DRG) was related to the pain vulnerability. Following nerve injury, the expression of SIRT1 in DRG was decreased in adult rodents while increased in juvenile rodents. Differential manipulation of SIRT1 abolished the different pain vulnerability between adult and juvenile rodents. Furthermore, SIRT1 interacted with ClC-3 channel and mediated ClC-3 membrane trafficking and Cl¯ current in DRG neurons. Differential manipulation of ClC-3 also abolished the difference in pain vulnerability between adult and juvenile rodents. The different anti-inflammatory ability determined the different change trends of SIRT1 and ClC-3 trafficking contributed to the different pain vulnerability in adult and juvenile rodents. In addition, the serum SIRT1 level was negatively correlated with pain score in chronic pain patients. These findings revealed the mechanism of the difference in pain vulnerability between adult and juvenile rodents and provided evidence for age-specific treatment of chronic pain.

5.
Angiology ; 72(1): 78-85, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32812445

RESUMO

The smoker's paradox refers to an increased risk of adverse clinical outcomes after smoking cessation in patients with coronary artery disease. The mechanisms involved are controversial. The present study evaluated the effect of delay in smoking cessation on clinical outcomes among patients after percutaneous coronary intervention (PCI) stratified by diabetes mellitus (DM). Patients included in this study came from an established Fu Wai hospital PCI cohort. Smoking behavior was recorded; clinical end points included all-cause mortality and repeat revascularization. The analyses were based on 8489 smokers who underwent PCI. Patients with and without DM were examined separately. Multivariable model analysis suggested that smoking cessation was associated with significant lower all-cause mortality both for non-DM and DM patients. The smoking paradox was observed for revascularization. However, the increased risk of repeat revascularization correlated with quitting time among non-DM patients only, especially if they stopped smoking late (>90 days) after their index procedure (adjusted hazard ratio, 3.40; 95% CI: 2.45-4.72). In conclusion, smoking cessation is associated with a lower mortality rate for PCI patients. However, the relative benefit on repeated revascularization was only observed among non-DM patients if they quit smoking early.


Assuntos
Doença da Artéria Coronariana/terapia , Diabetes Mellitus/epidemiologia , Intervenção Coronária Percutânea , Abandono do Hábito de Fumar , Estudos de Coortes , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fumantes , Fatores de Tempo
6.
J Stroke Cerebrovasc Dis ; 30(3): 105551, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33348248

RESUMO

OBJECTIVES: The efficacy of thrombolytic therapy with tissue plasminogen activator (tPA) is highly time dependent. Although clinical guidelines do not recommend written informed consent as it may cause treatment delays, local policy can supersede and require it. From 2014 to 2017, three out of five public hospitals in Singapore changed from written to verbal consent at different time points. We aimed to examine the association of hospital policy changes regarding informed consent on door-to-needle (DTN) times. MATERIALS AND METHODS: Using data from the Singapore Stroke Registry and surveys of local practice, we analyzed data of 915 acute ischemic stroke patients treated with tPA within 3 hours in all public hospitals between July 2014 to Dec 2017. Patient-level DTN times before and after policy changes were examined while adjusting for clinical characteristics, within-hospital clustering, and trends over time. RESULTS: Patient characteristics and stroke severity were similar before and after the policy changes. Overall, the median DTN times decreased from 68 to 53 minutes after the policy changes. After risk adjustment, changing from written to verbal informed consent was associated with a 5.6 minutes reduction (95% CI 1.1-10.0) in DTN times. After the policy changed, the percentage of patients with DTN ≤60 minutes and ≤45 minutes increased from 35.6% to 66.1% (adjusted OR 1.75; 95% CI 1.12-2.74) and 9.3% to 36.0% (adjusted OR 2.42; 95% CI 1.37-4.25), respectively. CONCLUSION: Changing from written to verbal consent is associated with significant improvement in the timeliness of tPA administration in acute ischemic stroke.

7.
Circ Cardiovasc Qual Outcomes ; : CIRCOUTCOMES120007150, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33302714

RESUMO

Background The benefit of intravenous thrombolytic therapy for acute ischemic stroke is time dependent. To assist hospitals in providing faster thrombolytic treatment, the American Heart Association launched target: stroke quality initiative in January 2010 which disseminated feasible strategies to shorten door-to-needle times for thrombolytic therapy. This study aimed to examine whether target: stroke was associated with improved door-to-needle times and 1-year outcomes. Methods We analyzed Medicare beneficiaries aged ≥65 years receiving intravenous thrombolytic treatment for acute ischemic stroke at 1490 Get With The Guidelines-Stroke hospitals during January 2006 and December 2009 (preintervention, n=10 804) and January 2010 and December 2014 (postintervention, n=31 249). The median age was 80 years and 42.7% were male. Results The median door-to-needle times decreased from 80 minutes for the preintervention to 68 minutes for the postintervention (P<0.001). The proportion of patients receiving intravenous thrombolysis with door-to-needle times 45 minutes and 60 minutes increased from 9.6% and 24.8% for preintervention to 17.1% and 40.6% for postintervention, respectively (P<0.001). The annual rate of increase in the door-to-needle times of 60 minutes or less accelerated from 0.20% (95% CI, -0.43% to 0.83%) per each 4 quarters for preintervention to 5.68% (95% CI, 5.23%-6.13%) for postintervention (P<0.001) which was further confirmed in piecewise multivariable generalized estimating analysis (adjusted odds ratio, 1.27 [95% CI, 1.19-1.35]). Cox proportional hazards analysis, after adjusting for patient and hospital characteristics and within-hospital clustering, showed that target: stroke was associated with lower all-cause readmission (40.4% versus 44.1%; hazard ratio, 0.91 [95% CI, 0.88-0.95]), cardiovascular readmission (19.7% versus 22.9%; hazard ratio, 0.85 [95% CI, 0.80-0.89]), and composite of all-cause mortality or readmission (56.0% versus 58.4%; hazard ratio, 0.96 [95% CI, 0.93-1.00]). The risk decline in all-cause mortality dissipated after risk adjustment (adjusted hazard ratio, 0.98 [95% CI, 0.94-1.02]). Conclusions Target: stroke quality initiative was associated with faster thrombolytic treatment times for acute ischemic stroke and modestly lower 1-year all-cause and cardiovascular readmissions.

8.
Chin Med J (Engl) ; 134(1): 8-19, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33323806

RESUMO

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, placing an increasing burden on human health. NAFLD is a complex multifactorial disease involving genetic, metabolic, and environmental factors. It is closely associated with metabolic syndrome, obesity, and type 2 diabetes, of which insulin resistance is the main pathophysiological mechanism. Over the past few decades, investigation of the pathogenesis, diagnosis, and treatments has revealed different aspects of NAFLD, challenging the accuracy of definition and therapeutic strategy for the clinical practice. Recently, experts reach a consensus that NAFLD does not reflect the current knowledge, and metabolic (dysfunction) associated fatty liver disease (MAFLD) is suggested as a more appropriate term. The new definition puts increased emphasis on the important role of metabolic dysfunction in it. Herein, the shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy of the newly defined MAFLD, as compared with the formerly defined NAFLD, are reviewed for updating our understanding.

9.
Nat Commun ; 11(1): 6381, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318506

RESUMO

A key feature that differentiates prokaryotic cells from eukaryotes is the absence of an intracellular membrane surrounding the chromosomal DNA. Here, we isolate a member of the ubiquitous, yet-to-be-cultivated phylum 'Candidatus Atribacteria' (also known as OP9) that has an intracytoplasmic membrane apparently surrounding the nucleoid. The isolate, RT761, is a subsurface-derived anaerobic bacterium that appears to have three lipid membrane-like layers, as shown by cryo-electron tomography. Our observations are consistent with a classical gram-negative structure with an additional intracytoplasmic membrane. However, further studies are needed to provide conclusive evidence for this unique intracellular structure. The RT761 genome encodes proteins with features that might be related to the complex cellular structure, including: N-terminal extensions in proteins involved in important processes (such as cell-division protein FtsZ); one of the highest percentages of transmembrane proteins among gram-negative bacteria; and predicted Sec-secreted proteins with unique signal peptides. Physiologically, RT761 primarily produces hydrogen for electron disposal during sugar degradation, and co-cultivation with a hydrogen-scavenging methanogen improves growth. We propose RT761 as a new species, Atribacter laminatus gen. nov. sp. nov. and a new phylum, Atribacterota phy. nov.


Assuntos
Estruturas da Membrana Celular/ultraestrutura , Rhizobiaceae/classificação , Rhizobiaceae/citologia , Rhizobiaceae/isolamento & purificação , Bactérias Anaeróbias , Composição de Bases , Estruturas da Membrana Celular/genética , DNA Bacteriano/genética , Ácidos Graxos , Fermentação , Genoma Bacteriano , Sedimentos Geológicos/microbiologia , Japão , Filogenia , RNA Ribossômico 16S , Rhizobiaceae/genética , Análise de Sequência de DNA
10.
Org Lett ; 22(22): 8808-8813, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33151078

RESUMO

Controllable rhodium(III)-catalyzed tandem [3+2] cyclization of aromatic aldehydes with maleimides is developed for the divergent synthesis of stereoselective indane-fused pyrrolidine-2,5-dione. Switchable access to different products could be achieved by employing different additives and varying the reaction time. This atom-economic transformation proceeds efficiently via the C-H bond activation directed by weakly coordinating aldehydes and is characterized by exclusive stereoselectivity, air atmosphere, and being free of nitrogen-based transient directing groups.

11.
World J Gastroenterol ; 26(39): 6057-6073, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33132655

RESUMO

BACKGROUND: The activity staging of Crohn's disease (CD) in the terminal ileum is critical in developing an accurate clinical treatment plan. The activity of terminal ileum CD is associated with the microcirculation of involved bowel walls. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) can reflect perfusion and permeability of bowel walls by providing microcirculation information. As such, we hypothesize that DCE-MRI and DWI parameters can assess terminal ileum CD, thereby providing an opportunity to stage CD activity. AIM: To evaluate the value of DCE-MRI and DWI in assessing activity of terminal ileum CD. METHODS: Forty-eight patients with CD who underwent DCE-MRI and DWI were enrolled. The patients' activity was graded as remission, mild and moderate-severe. The transfer constant (Ktrans), wash-out constant (Kep), and extravascular extracellular volume fraction (Ve) were calculated from DCE-MRI and the apparent diffusion coefficient (ADC) was obtained from DWI. Magnetic Resonance Index of Activity (MaRIA) was calculated from magnetic resonance enterography. Differences in these quantitative parameters were compared between normal ileal loop (NIL) and inflamed terminal ileum (ITI) and among different activity grades. The correlations between these parameters, MaRIA, the Crohn's Disease Activity Index (CDAI), and Crohn's Disease Endoscopic Index of Severity (CDEIS) were examined. Receiver operating characteristic curve analyses were used to determine the diagnostic performance of these parameters in differentiating between CD activity levels. RESULTS: Higher Ktrans (0.07 ± 0.04 vs 0.01 ± 0.01), Kep (0.24 ± 0.11 vs 0.15 ± 0.05) and Ve (0.27 ± 0.07 vs 0.08 ± 0.03), but lower ADC (1.41 ± 0.26 vs 2.41 ± 0.30) values were found in ITI than in NIL (all P < 0.001). The Ktrans, Kep, Ve and MaRIA increased with disease activity, whereas the ADC decreased (all P < 0.001). The Ktrans, Kep, Ve and MaRIA showed positive correlations with the CDAI (r = 0.866 for Ktrans, 0.870 for Kep, 0.858 for Ve, 0.890 for MaRIA, all P < 0.001) and CDEIS (r = 0.563 for Ktrans, 0.567 for Kep, 0.571 for Ve, 0.842 for MaRIA, all P < 0.001), while the ADC showed negative correlations with the CDAI (r = -0.857, P < 0.001) and CDEIS (r = -0.536, P < 0.001). The areas under the curve (AUC) for the Ktrans, Kep, Ve, ADC and MaRIA values ranged from 0.68 to 0.91 for differentiating inactive CD (CD remission) from active CD (mild to severe CD). The AUC when combining the Ktrans, Kep and Ve was 0.80, while combining DCE-MRI parameters and ADC values yielded the highest AUC of 0.95. CONCLUSION: DCE-MRI and DWI parameters all serve as measures to stage CD activity. When they are combined, the assessment performance is improved and better than MaRIA.

12.
Front Microbiol ; 11: 588841, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193249

RESUMO

The family Nosodendridae is a small group of tree sap beetles with only 91 described species representing three genera from the world. In 1930s, bacteria-harboring symbiotic organs, called bacteriomes, were briefly described in a European species Nosodendron fasciculare. Since then, however, no studies have been conducted on the nosodendrid endosymbiosis for decades. Here we investigated the bacteriomes and the endosymbiotic bacteria of Nosodendron coenosum and Nosodendron asiaticum using molecular phylogenetic and histological approaches. In adults and larvae, a pair of slender bacteriomes were found along both sides of the midgut. The bacteriomes consisted of large bacteriocytes at the center and flat sheath cells on the surface. Fluorescence in situ hybridization detected preferential localization of the endosymbiotic bacteria in the cytoplasm of the bacteriocytes. In reproductive adult females, the endosymbiotic bacteria were also detected at the infection zone in the ovarioles and on the surface of growing oocytes, indicating vertical symbiont transmission via ovarial passage. Transmission electron microscopy unveiled bizarre structural features of the bacteriocytes, whose cytoplasm exhibited degenerate cytology with deformed endosymbiont cells. Molecular phylogenetic analysis revealed that the nosodendrid endosymbionts formed a distinct clade in the Bacteroidetes. The nosodendrid endosymbionts were the most closely related to the bacteriome endosymbionts of bostrichid powderpost beetles and also allied to the bacteriome endosymbionts of silvanid grain beetles, uncovering an unexpected endosymbiont relationship across the unrelated beetle families Nosodendridae, Bostrichidae and Silvanidae. Host-symbiont co-evolution and presumable biological roles of the endosymbiotic bacteria are discussed.

13.
J Clin Lab Anal ; : e23616, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084078

RESUMO

BACKGROUND: Seoul virus (SEOV) is a Hantavirus and the causative pathogen of Hemorrhagic Fever with Renal Syndrome (HFRS). Diagnosing SEOV infection is difficult because the clinical presentations are often undistinguishable from other viral or bacterial infections. In addition, diagnostic tools including serological and molecular assays are not readily available in the clinical settings. CASE REPORT: A 57-year-old male presented with fever and a sudden loss of consciousness in November 2019. Computed tomography (CT) scan showed subdural hematoma, subfalcine herniation, and brain infarction. He developed thrombocytopenia and elevated transaminases, but no rashes or obvious kidney damage. He reported having a rat bite. HFRS was suspected. The Hantavirus IgG was positive, and the metagenomic next-generation sequencing (mNGS) detected SEOV sequences directly in the blood. CONCLUSION: This report highlights the importance of suspecting SEOV infection in febrile patients with thrombocytopenia and elevated liver enzymes despite the absence of hemorrhagic manifestations of skin and renal syndromes. Next-generation sequencing is a powerful tool for pathogen detection. Intracranial hemorrhage and brain infarction as extrarenal manifestations of HFRS are rare but possible as demonstrated in this case.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33002913

RESUMO

OBJECTIVE: Investigate whether the elimination of trial admissions and the initiation of documentation requirements, via the 2010 Centers for Medicare and Medicaid Services (CMS) Inpatient Rehabilitation Facility (IRF) Prospective Payment System (PPS) Rule, limited IRF access while increasing skilled nursing facility (SNF) utilization compared to home discharge (HD) in ischemic stroke (IS) patients. DESIGN: Retrospective observational study using Get with the Guidelines - Stroke hospital data between 1/1/2008 and 12/31/2015 (n=1,643,553). RESULTS: Between 1/1/2008 and 12/31/2009, 54.1% of patients went home, 25.4% to IRF, 20.5% to SNF. Between 1/1/2010 and 12/31/2015, there was a 1.4% absolute increase in HD, a 1.1% IRF decline, and a 0.3% SNF decline.Within the 1.1% absolute decline in IRF discharge, the adjusted odds of IRF versus HD decreased 12% post 2010 Rule (aOR 0.88, 95% CI 0.87 - 0.89; P<0.0001). There was no statistically significant change in SNF versus HD.Lower adjusted odds of IRF discharge versus HD were identical across age groups and were present in all geographic regions. CONCLUSIONS: In populations with ischemic stroke, the CMS 2010 IRF PPS Rule was associated with a 1.1% absolute decrease in IRF discharge, with a concomitant increase in HD rather than to SNF.

15.
Pain ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32868747

RESUMO

Mechanical allodynia is a debilitating condition for millions of patients with chronic pain. Mechanical allodynia can manifest in distinct forms, including brush-evoked dynamic and filament-evoked static allodynia. In the nervous system, the forkhead protein Foxo1 plays a critical role in neuronal structures and functions. However, the role of Foxo1 in the somatosensory signal remains unclear. Here, we found that Foxo1 selectively regulated static mechanical pain. Foxo1 knockdown decreased sensitivity to static mechanical stimuli in normal rats and attenuated static mechanical allodynia in rat models for neuropathic, inflammatory, and chemotherapy pain. Conversely, Foxo1 overexpression selectively enhanced sensitivity to static mechanical stimuli and provoked static mechanical allodynia. Furthermore, Foxo1 interacted with voltage-gated sodium Nav1.7 channels and increased the Nav1.7 current density by accelerating activation rather than by changing the expression of Nav1.7 in dorsal root ganglia neurons. In addition, the serum level of Foxo1 was found to be increased in chronic pain patients and to be positively correlated with the severity of chronic pain. Altogether, our findings suggest that serum Foxo1 level could be used as a biological marker for prediction and diagnosis of chronic pain. Moreover, selective blockade of Foxo1/Nav1.7 interaction may offer a new therapeutic approach in patients with mechanical pain.

16.
FASEB J ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32964547

RESUMO

Acute kidney injury (AKI) is a highly prevalent clinical syndrome with high mortality and morbidity. Previous studies indicated that inflammation promotes tubular damage and plays a key role in AKI progress. Spleen tyrosine kinase (Syk) has been linked to macrophage-related inflammation in AKI. Up to date, however, no Syk-targeted therapy for AKI has been reported. In this study, we employed both cell model of LPS-induced bone marrow-derived macrophage (BMDM) and mouse model of ischemia/reperfusion injury (IRI)-induced AKI to evaluate the effects of a Syk inhibitor, BAY61-3606 (BAY), on macrophage inflammation in vitro and protection of kidney from AKI in vivo. The expression and secretion of inflammatory cytokines, both in vitro and in vivo, were significantly inhibited even back to normal levels by BAY. The upregulated serum creatinine and blood urea nitrogen levels in the AKI mice were significantly reduced after administration of BAY, implicating a protective effect of BAY on kidneys against IRI. Further analyses from Western blot, immunofluorescence staining and flow cytometry revealed that BAY inhibited the Mincle/Syk/NF-κB signaling circuit and reduced the inflammatory response. BAY also inhibited the reactive oxygen species (ROS), which further decreased the formation of inflammasome and suppressed the mature of IL-1ß and IL-18. Notably, these inhibitory effects of BAY on inflammation and inflammasome in BMDM were significantly reversed by Mincle ligand, trehalose-6,6-dibehenate. In summary, these findings provided compelling evidence that BAY may be an efficient inhibitor of the Mincle/Syk/NF-κB signaling circuit and ROS-induced inflammasome, which may help to develop Syk-inhibitors as novel therapeutic agents for AKI.

17.
Front Neurol ; 11: 961, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982952

RESUMO

Randomized Controlled Trials (RCTs) are considered the gold standard for measuring the efficacy of medical interventions. However, RCTs are expensive, and use a limited population. Techniques to estimate the effects of stroke interventions from observational data that minimize confounding would be useful. We used regression discontinuity design (RDD), a technique well-established in economics, on the Get With The Guidelines-Stroke (GWTG-Stroke) data set. RDD, based on regression, measures the occurrence of a discontinuity in an outcome (e.g., odds of home discharge) as a function of an intervention (e.g., alteplase) that becomes significantly more likely when crossing the threshold of a continuous variable that determines that intervention (e.g., time from symptom onset, since alteplase is only given if symptom onset is less than e.g., 3 h). The technique assumes that patients near either side of a threshold (e.g., 2.99 and 3.01 h from symptom onset) are indistinguishable other than the use of the treatment. We compared outcomes of patients whose estimated onset to treatment time fell on either side of the treatment threshold for three cohorts of patients in the GWTG-Stroke data set. This data set spanned three different treatment thresholds for alteplase (3 h, 2003-2007, N = 1,869; 3 h, 2009-2016, N = 13,086, and 4.5 h, 2009-2016, N = 6,550). Patient demographic characteristics were overall similar across the treatment thresholds. We did not find evidence of a discontinuity in clinical outcome at any treatment threshold attributable to alteplase. Potential reasons for failing to find an effect include violation of some RDD assumptions in clinical care, large sample sizes required, or already-well-chosen treatment threshold.

18.
Stroke Vasc Neurol ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973114

RESUMO

BACKGROUND: The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China. We investigated whether the implementation of a citywide Acute Stroke Care Map (ASCaM) is associated with an improvement of acute stroke care quality in a Chinese urban area. METHODS: The ASCaM comprises 10 improvement strategies and has been implemented through a network consisting of 20 tertiary hospitals. We identified 7827 patients with ischaemic stroke admitted from April to October 2017, and 506 patients underwent thrombolysis were finally included for analysis. RESULTS: Compared with 'pre-ASCaM period', we observed an increased rate of administration of tissue plasminogen activator within 4.5 hours (65.4% vs 54.5%; adjusted OR, 1.724; 95% CI 1.21 to 2.45; p=0.003) during 'ASCaM period'. In multivariate analysis models, 'ASCaM period' was associated with a significant reduction in onset-to-door time (114.1±55.7 vs 135.7±58.4 min, p=0.0002) and onset-to-needle time (ONT) (169.2±58.1 vs 195.6±59.3 min, p<0.0001). Yet no change was found in door-to-needle time. Clinical outcomes such as symptomatic intracranial haemorrhage, favourable functional outcome (modified Rankin Scale ≤2) and in-hospital mortality remained unchanged. CONCLUSION: The implementation of ASCaM was significantly associated with increased rates of intravenous thrombolysis and shorter ONT. The ASCaM may, in proof-of-principle, serve as a model to reduce treatment delay and increase thrombolysis rates in Chinese urban areas and possibly other highly populated Asian regions.

19.
Zoolog Sci ; 37(5): 399-410, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32972080

RESUMO

Cockroaches are commonly found in human residences and notorious as hygienic and nuisance pests. Notably, however, no more than 30 cockroach species are regarded as pests, while the majority of 4,500 cockroaches in the world are living in forest environments with little relevance to human life. Why some cockroaches have exceptionally adapted to anthropic environments and established pest status is of interest. Here we investigated the German cockroach Blattella germanica, which is a cosmopolitan pest species, and the forest cockroach Blattella nipponica, which is a wild species closely related to B. germanica. In contrast to easy rearing of B. germanica, laboratory rearing of B. nipponica was challenging-several trials enabled us to keep the insects for up to three months. We particularly focused on the distribution patterns of specialized cells, bacteriocytes, for harboring endosymbiotic Blattabacterium, which has been suggested to contribute to host's nitrogen metabolism and recycling, during the postembryonic development of the insects. The bacteriocytes were consistently localized to visceral fat bodies filling the abdominal body cavity, where a number of single bacteriocytes were scattered among the adipocytes, throughout the developmental stages in both females and males. The distribution patterns of the bacteriocytes were quite similar between B. germanica and B. nipponica, and also among other diverse cockroach species, plausibly reflecting the highly conserved cockroach-Blattabacterium symbiotic association over evolutionary time. Our study lays a foundation to experimentally investigate the origin and the processes of urban pest evolution, on account of possible involvement of microbial associates.

20.
JAMA Neurol ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32955582

RESUMO

Importance: A significant proportion of acute ischemic strokes occur while patients are hospitalized. Limited contemporary data exist on the utilization rates of intravenous thrombolysis or endovascular therapy for in-hospital stroke. Objective: To use a national registry to examine temporal trends in the use of intravenous and endovascular reperfusion therapies for treatment of in-hospital stroke. Design, Setting, and Participants: This retrospective cohort study analyzed data from 267 956 patients who underwent reperfusion therapy for stroke with in-hospital or out-of-hospital onset reported in the Get With the Guidelines-Stroke national registry from January 2008 to September 2018. Exposures: In-hospital onset vs out-of-hospital onset of stroke symptoms. Main Outcomes and Measures: Temporal trends in the use of reperfusion therapy, process measures of quality, and the association between functional outcomes and key patient characteristics, comorbidities, and treatments. Results: Of 67 493 patients with in-hospital stroke onset, this study observed increased rates of vascular risk factors (standardized mean difference >10%) but no significant differences in age or sex in patients undergoing intravenous thrombolysis only (mean [interquartile range {IQR}] age, 72 [80-62] y; 53.2% female) or those undergoing endovascular therapy (mean [IQR] age, 69 [59-79] y; 49.8% female). Of these patients, 10 481 (15.5%) received intravenous thrombolysis and 2494 (3.7%) underwent endovascular therapy. Compared with 2008, in 2018 the proportion of in-hospital stroke among all stroke hospital discharges was higher (3.5% vs 2.7%; P < .001), as was use of intravenous thrombolysis (19.1% vs 9.1%; P < .001) and endovascular therapy (6.4% vs 2.5%; P < .001) in patients with in-hospital stroke, with a significant increase in endovascular therapy in mid-2015 (P < .001). Compared with patients who received intravenous thrombolysis for out-of-hospital stroke onset, those with in-hospital onset were associated with longer median (IQR) times from stroke recognition to cranial imaging (33 [18-60] vs 16 [9-26] minutes; P < .001) and to thrombolysis bolus (81 [52-125] vs 60 [45-84] minutes; P < .001). In adjusted analyses, patients with in-hospital stroke onset who were treated with intravenous thrombolysis were less likely to ambulate independently at discharge (adjusted odds ratio, 0.78; 95% CI, 0.74-0.82; P < .001) and were more likely to die or to be discharged to hospice (adjusted odds ratio, 1.39; 95% CI, 1.29-1.50; P < .001) than patients with out-of-hospital onset who also received intravenous thrombolysis treatment. Comparisons among patients treated with endovascular therapy yielded similar findings. Conclusions and Relevance: In this cohort study, in-hospital stroke onset was increasingly reported and treated with reperfusion therapy. Compared with out-of-hospital stroke onset, in-hospital onset was associated with longer delays to reperfusion and worse functional outcomes, highlighting opportunities to further care for patients with in-hospital stroke onset.

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