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1.
Eur Rev Med Pharmacol Sci ; 24(5): 2218-2228, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32196573

RESUMO

OBJECTIVE: Osteosarcoma (OS) is a frequent bone malignancy. Long non-coding RNA myocardial infarction associated transcript (MIAT) has been reported to be involved in the development of human cancers, including OS. However, the mechanism underlying MIAT in OS progression remains largely unclear. PATIENTS AND METHODS: The expression levels of MIAT and sineoculis homeobox homolog 1 (SIX1) in OS tissues and cells were detected by quantitative real-time polymerase chain reaction and Western blot. Cell viability, apoptosis, migration and invasion of OS cells were determined by MTT, flow cytometry and trans-well assays, respectively. The target interaction among MIAT, miR-141-3p and SIX1 was analyzed by bioinformatics analysis and luciferase reporter assay. Phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT) pathway was evaluated by Western blot. RESULTS: MIAT and SIX1 expression levels were enhanced in OS tissues and cells. Knockdown of MIAT or SIX1 repressed cell viability, migration and invasion but promoted apoptosis in OS cells. Moreover, overexpression of SIX1 reversed the inhibitive role of MIAT silence in OS progression. Furthermore, MIAT could increase SIX1 expression by competitively sponging miR-141-3p. Besides, inhibition of MIAT blocked PI3K/AKT pathway by decreasing SIX1 in OS cells. CONCLUSIONS: MIAT silence suppresses OS progression through inactivating PI3K/AKT signaling by sponging miR-141-3p to regulate SIX1, indicating a novel target for the treatment of OS.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32202813

RESUMO

Methamphetamine (MA) is a highly addictive stimulant with recent upward trends in prevalence and associated public health problems. Drug demand, as assessed by hypothetical purchasing tasks, has been useful in addictions research and may help our understanding of the factors influencing MA use. However, no studies have assessed MA demand using current models of demand. The purpose of the current study was to assess demand for MA using a hypothetical drug purchasing task. Given high rates of cigarette smoking among MA users, it was of interest also to assess and compare demand for MA relative to cigarettes. Participants consisted of non-treatment-seeking volunteers with MA use disorder (N = 18), of whom 17 reported daily smoking. Results showed the exponentiated demand model provided a good fit to consumption data. Results from Bayesian generalized linear modeling demonstrated multiple positive relationships (posterior probability ≥75%) between self-reported drug use (days MA used in the past 30 days, cigarettes smoked per day) and indices of demand for each drug (Qo, Omax, Pmax, and break point). Comparing MA to cigarettes, results from Bayesian generalized linear mixed modeling revealed greater abuse liability for MA compared to cigarettes (posterior probability ≥99%) based on α and essential value. Overall, the findings of the current study support the feasibility and validity of the exponentiated demand model for assessing demand for drugs among individuals with MA use disorder. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

3.
Mol Oncol ; 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32146726

RESUMO

The proviral integration site for Moloney murine leukemia virus (PIM) serine/threonine kinases have an oncogenic and prosurvival role in hematological and solid cancers. However, the mechanism by which these kinases drive tumor growth has not been completely elucidated. To determine the genes controlled by these protein kinases, we carried out a microarray analysis in T-cell acute lymphoblastic leukemia (T-ALL) comparing early progenitor (ETP-ALL) cell lines whose growth is driven by PIM kinases to more mature T-ALL cells that have low PIM levels. This analysis demonstrated that the long noncoding RNA (lncRNA) H19 was associated with increased PIM levels in ETP-ALL. Overexpression or knockdown of PIM in these T-ALL cell lines controlled the level of H19 and regulated the methylation of the H19 promoter, suggesting a mechanism by which PIM controls H19 transcription. In these T-ALL cells, the expression of PIM1 induced stem cell gene expression (SOX2, OCT-4, and NANOG) through H19. Identical results were found in prostate cancer (PCa) cell lines where PIM kinases drive cancer growth, and both H19 and stem cell gene levels. Small molecule pan-PIM inhibitors (PIM-i) currently in clinical trials reduced H19 expression in both of these tumor types. Importantly, the knockdown of H19 blocked the ability of PIM to induce stem cell genes in T-ALL cells, suggesting a novel signal transduction cascade. In PCa, increases in SOX2 levels have been shown to cause both resistance to the androgen deprivation therapy (ADT) and the induction of neuroendocrine PCa, a highly metastatic form of this disease. Treatment of PCa cells with a small molecule pan-PIM-i reduced stem cell gene transcription and enhanced ADT, while overexpression of H19 suppressed the ability of pan-PIM-i to regulate hormone blockade. Together, these results demonstrate that the PIM kinases control the level of lncRNA H19, which in turn modifies stem cell gene transcription regulating tumor growth.

4.
Nat Chem Biol ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094923

RESUMO

Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease. Historically, therapeutics targeting RTKs have been identified using in vitro kinase assays. Due to frequent development of drug resistance, however, there is a need to identify more diverse compounds that inhibit mutated but not wild-type RTKs. Here, we describe MaMTH-DS (mammalian membrane two-hybrid drug screening), a live-cell platform for high-throughput identification of small molecules targeting functional protein-protein interactions of RTKs. We applied MaMTH-DS to an oncogenic epidermal growth factor receptor (EGFR) mutant resistant to the latest generation of clinically approved tyrosine kinase inhibitors (TKIs). We identified four mutant-specific compounds, including two that would not have been detected by conventional in vitro kinase assays. One of these targets mutant EGFR via a new mechanism of action, distinct from classical TKI inhibition. Our results demonstrate how MaMTH-DS is a powerful complement to traditional drug screening approaches.

7.
Eur Rev Med Pharmacol Sci ; 24(2): 728-734, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32016975

RESUMO

OBJECTIVE: Recently, long noncoding RNAs (lncRNAs) have attracted much attention for their roles in tumor progression. The aim of this study was to investigate the exact role of lncRNA UCA1 in the development of thyroid cancer (TC) and to explore the possible underlying mechanism. PATIENTS AND METHODS: UCA1 expression in both TC cells and tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Colony formation assay, cell proliferation, and transwell assay were conducted in vitro. Subsequent luciferase reporter gene assay was applied to investigate the underlying mechanism. Furthermore, the function of UCA1 in vivo was monitored as well. RESULTS: UCA1 expression level in TC samples was significantly higher than that of corresponding normal tissues. After UCA1 was knocked down in vitro and in vivo, the proliferation, migration, and invasion of TC cells were significantly inhibited. Moreover, the expression of miR-497-3p was repressed after the knockdown of UCA1. Furthermore, miR-497-3p was directly targeted by UCA1. CONCLUSIONS: Knockdown of UCA1 could inhibit TC cell proliferation and metastasis via sponging miR-497-3p. Our findings might offer a new therapeutic intervention for TC patients.

8.
Eur Rev Med Pharmacol Sci ; 24(1): 200-212, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31957833

RESUMO

OBJECTIVE: Tongue cancer is a common malignant tumor in the oral and maxillofacial region, most of which is squamous cell carcinoma. Cisplatin (DDP) is one of the chemotherapy drugs for patients with tongue squamous cell carcinoma (TSCC). However, DDP resistance has become a major obstacle to its clinical application. Our study aimed to investigate the effects of long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) on DDP resistance of tongue cancer and the underlying mechanism. PATIENTS AND METHODS: The levels of KCNQ1OT1, miR-124-3p, and tripartite motif containing 14 (TRIM14) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The maximum size of tumor (MTS) assay was used to detect the cell survival rates. Furthermore, the cell proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was performed to detect the cell migration and invasion. Western blot assay was used to detect the protein levels of Vimentin, N-cadherin, E-cadherin, and TRIM14. The functional targets of KCNQ1OT1 and miR-124-3p, miR-124-3p and TRIM14 were predicted by starBase 3.0 and TargetScan. The relationship between KCNQ1OT1 and miR-124-3p was confirmed by Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down. Further, the relationship between miR-124-3p and TRIM14 was verified by Dual-Luciferase reporter assay. Animal experiment revealed the effect of KCNQ1OT1 on DDP resistance of tongue cancer cells in vivo. RESULTS: KCNQ1OT1 was upregulated in DDP-resistant tongue cancer tissues and cells, and mainly expressed in cytoplasm. Functionally, the knockdown of KCNQ1OT1 inhibited the survival rate, proliferation, migration, invasion, and EMT of the DDP-resistant tongue cancer cells. Of note, miR-124-3p acted as a target of KCNQ1OT1 and KCNQ1OT1 could reduce the expression of miR-124-3p. Moreover, miR-124-3p targeted TRIM14 and the downregulation of TRIM14 reduced the DDP resistance of tongue cancer cells. Importantly, KCNQ1OT1 regulated the TRIM14 expression by targeting miR-124-3p. Furthermore, KCNQ1OT1 knockdown reduced the DDP-resistant tumor growth and weight through the miR-124-3p/TRIM14 axis in vivo. CONCLUSIONS: LncRNA KCNQ1OT1 promotes the DDP resistance of tongue cancer by sponging miR-124-3p to regulate TRIM14 expression.

9.
Insect Mol Biol ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31908051

RESUMO

The striped rice stem borer, Chilo suppressalis Walker, is one of the most destructive rice pests in Asia. Insecticidal crystal proteins (Cry toxins) produced by Bacillus thuringiensis are widely used as biopesticides or in developing transgenic crops for pest management. In this study, we tested the involvement of two newly cloned C. suppressalis cadherins (CsCAD3 and CsCAD4) in the toxicity of Cry1Ab/Ac, Cry2Aa and Cry1Ca. Our results showed that CsCAD4 was expressed highest in the midgut, whereas CsCAD3 was expressed highest in the epidermis. The feeding of double-stranded RNA specific to CsCAD3 and CsCAD4 respectively significantly suppressed the expressions of target gene. The knockdown of CsCAD3 significantly reduced the mortality of larvae to Cry1Ab/Ac, whereas knockdown of CsCAD4 significantly decreased the larval susceptibility to Cry2Aa. In contrast, reduced expressions of CsCAD3 or CsCAD4 were not interacted with larval susceptibility to Cry1Ca. Our results suggest that CsCAD3 and CsCAD4 function in Cry toxin toxicity and these findings will help us to better understand the action mechanism of Cry toxins in C. suppressalis.

10.
Head Neck ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31930773

RESUMO

BACKGROUND: We aimed to evaluate the oncological impact of hypothyroidism and levothyroxine (LT) supplementation after hemithyroidectomy in patients with papillary thyroid carcinoma (PTC). METHODS: We retrospectively examined 401 patients who underwent hemithyroidectomy for classic PTC and who were postoperatively followed-up with ≥3 thyroid function measurements for ≥24 months. RESULTS: During 77.4 months of follow-up, 268/401 patients (66.8%) developed hypothyroidism and 19/401 patients (4.7%) showed recurrence. Recurrence rates did not differ between the euthyroidism and hypothyroidism development groups. Recurrence rates were significantly lower in the LT group than in the no-LT group, although mean postoperative thyroid-stimulating hormone (TSH) levels were not different between the two groups. Univariate and multivariate analysis showed that tumors sized >1 cm and lack of LT supplementation were significantly associated with recurrence. CONCLUSIONS: Postoperative hypothyroidism development was not a risk factor for PTC recurrence after hemithyroidectomy. Nevertheless, LT supplementation reduced recurrence risk without suppressing TSH.

11.
Drug Alcohol Depend ; 206: 107740, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778948

RESUMO

BACKGROUND: Delay discounting (DD) research has improved our understanding of important behavioral processes associated with tobacco use. Little research has explored DD among e-cigarette users, and these studies have exclusively examined money as the only available commodity. This secondary analysis of a laboratory study explored discounting for money and e-liquid among e-cigarette users using two single-commodity discounting (SCD) tasks and one cross-commodity discounting (CCD) task. A secondary goal was to explore the extent to which results from the SCD and CCD tasks were correlated to each other and with measures of e-cigarette use. METHODS: E-cigarette users (N = 27) completed two SCD tasks and one CCD task. The SCD tasks assessed choices between various amounts of either money now versus money later (M-M) or e-liquid now versus e-liquid later (mL-mL). The CCD task assessed choices between e-liquid now versus money later (mL-M). Discounting results were compared using logk and AUClog. RESULTS: Discounting was greatest in the mL-mL task, followed by the M-M task, and then the mL-M task. AUClog and logk were significantly correlated across all discounting tasks. Attempts to quit vaping was positively associated with logk and negatively associated with AUClog and in both SCD tasks. CONCLUSIONS: E-cigarette users discount e-liquid more than money in a SCD task. However, when the two commodities, money and e-liquid (CCD), are compared the substance of abuse is discounted to a lesser extent. Interventions that provide alternative reinforcers to compete with the reinforcing effects of nicotine intake may be especially indicated for treating e-cigarette dependence.

13.
Br J Dermatol ; 182(1): e3, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31489984
14.
Psychol Addict Behav ; 34(1): 164-174, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31233323

RESUMO

Cocaine use disorder (CUD) is a significant public health issue. Behavioral interventions such as contingency management (CM) have been demonstrated to be highly effective in promoting cocaine abstinence. However, identifying individual characteristics associated with cocaine relapse may help improve treatment outcomes. Cocaine demand is a behavioral economic measure that shares a scientific foundation with CM. In the current study, we assessed baseline cocaine demand using a hypothetical cocaine purchasing task. Participants (N = 58) consisted of treatment-seeking individuals with CUD. All participants received 1 month of CM treatment for cocaine abstinence, and treatment responders were defined as presenting 6 consecutive cocaine negative urine samples from thrice weekly clinic visits. Demand data were well described by the exponentiated demand model. Indices of demand (intensity of demand [Q0], elasticity [α]) were significantly associated with recent (last 30 days) cocaine use. Importantly, linear regression revealed that CM treatment nonresponders presented significantly higher Q0 (p = .025). Subsequent quantile regression analyses examining the relationship between CM treatment response and Q0 revealed statistically reliable effects of being a nonresponder across 3 of the lower percentiles (i.e., 15, 25, and 30). Overall, these findings provide further support for the utility of exponentiated demand model. To our knowledge, this is the first study to demonstrate an association between baseline demand and contingency management response and systematically extend the findings of prior demand research to a novel drug class, cocaine. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

15.
J Emerg Trauma Shock ; 12(4): 280-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798243

RESUMO

Background: Delirium frequently affects older emergency department (ED) patients and has been associated with accelerated cognitive and functional decline, increased length of stay (LOS), and higher in- and out-of-hospital mortality. Objectives: Care provided in the ED may have downstream effects on delirium duration during hospitalization. This study aimed to identify the modifiable factors of ED care associated with delirium duration in patients admitted to the hospital through the ED. Materials and Methods: This prospective cohort study enrolled ED patients who were 65 years and older and admitted to the hospital. Delirium was determined in the ED and during the first 7 days of hospitalization using the modified Brief Confusion Assessment Method. All delirious patients and a random selection (17%) of nondelirious patients were also enrolled. ED LOS, opioid administration, benzodiazepine administration, anticholinergic medication administration, and bladder catheter placement were obtained by medical record review. Multivariable proportional odds logistic regression was performed to determine if each of the factors was associated with delirium duration after adjusting for age, dementia, baseline function, comorbidity burden, severity of illness, nursing home residence, and central nervous system insult. Results: A total of 228 patients were enrolled. ED bladder catheter placement was significantly associated (adjusted proportional odds ratio = 3.1, 95% confidence interval: 1.3 to 7.4) with increased delirium duration after adjusting for confounders. ED LOS, opioid administration, benzodiazepine administration, and anticholinergic burden, however, were not. Conclusions: ED bladder catheter placement was significantly associated with delirium duration and may present an opportunity for intervention.

16.
Zhonghua Yi Xue Za Zhi ; 99(46): 3627-3632, 2019 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-31826584

RESUMO

Objective: To find the best strategy of embryo transfer, so as to provide theoretical basis for improving the clinical outcomes of in vitro fertilization-Embryo transfer (IVF-ET), we investigate the blastocyst culture of surplus cleavage-stage embryos after D3 embryo transfer and the prediction of clinical outcomes with or without blastocyst formation. Methods: A retrospective study was conducted on 3 568 patients who underwent IVF-ET in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to May 2018, whotransplanted two embryos in D3 with blastocyst culture of surplus cleavage-stage embryos, according to their age, they were divided into three groups: <35 years old group, 35-38 years old group, and>38 years old group.And according to the presence or absence of blastocyst formation, they were also divided into two subgroups: blastocyst formation group and non-blastocyst formation group. The embryo development and clinical outcomes in each group were compared. Results: (1) Comparisons of the embryo development in the three age groups with the first cycle. The total fertilization rate, cleavage rate and high quality embryo rate of the blastocyst formation group in the three groups were higher than those in the non-blastocyst formation group, P<0.05; In<35 years old group, the embryo utilization rate (75.0% vs 70.6%), pregnancy rate (74.9% vs 70.3%), planting rate (53.6% vs 48.6%), delivery rate (66.7% vs 61.1%) and live birth rate (66.5% vs 61.0%) of the blastocyst formation group were higher than those in the non-blastocyst formation group, P<0.05. (2) Comparisons of embryo development in the three age groups with multiple cycles (≥2 cycles). In<35 years old group, the total fertilization rate (75.0% vs 70.6%),delivery rate (62.7% vs 43.8%) and live birth rate (62.7% vs 43.8%) of the blastocyst formation group were significantly higher than those in the non-blastocyst formation group, P<0.05; In>38 years old group, the pregnancy rate (56.3% vs 25.8%), implantation rate (34.4% vs 14.5%), delivery rate (43.8% vs 11.3%), live birth rate (43.8% vs 11.3%) of the blastocyst formation group were higher than those in the non-blastocyst formation group, P<0.05. Conclusions: The results of blastocyst culture in different groups can predict the outcomes of embryo transfer in D3. For patients<35 years old with the first cycle, the clinical outcomes of the blastocyst formation group after D3 embryo transfer is better than that of the non-blastocyst formation group. For Patients with multiple cycles (≥2 cycles),the clinical outcomes of the embryo formation group is superior to that of the non-blastocyst formation group<35 years old or>38 years old.


Assuntos
Blastocisto , Fase de Clivagem do Zigoto , Transferência Embrionária , Gravidez Múltipla , Adulto , Feminino , Fertilização In Vitro , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
17.
PLoS One ; 14(12): e0226412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856187

RESUMO

BACKGROUND: Delirium's pathophysiology is poorly understood. We sought to determine if plasma biomarkers of inflammation, coagulation, endothelial activation, and blood brain barrier (BBB) injury were associated with emergency department (ED) delirium duration. METHODS: We enrolled hospitalized patients who were 65 years or older from the ED. Plasma biomarkers of inflammation (interleukin-6 [IL-6], IL-8, soluble tumor necrosis factor receptor I [sTNFRI]), coagulation (Protein C), endothelial activation (plasminogen activating inhibitor-1 [PAI-1]), and BBB injury (S100B) at were measured using blood obtained at enrollment. The dependent variable was ED delirium duration which was determined by the Brief Confusion Assessment Method assessed in the ED and hospitalization. Proportional odds logistic regression analyses were performed adjusted for relevant confounders and allowing for interaction by baseline dementia status. RESULTS: A total of 156 patients were enrolled. IL-6 (POR = 1.59, 95%CI: 1.09-2.32) and PAI-1 (POR = 2.96, 95%CI: 1.48 to 6.85) were independently associated with more prominent ED delirium duration in subjects without dementia only. No significant associations between IL-8, Protein C, sTNRFI, and S100B and ED delirium duration were observed. CONCLUSIONS: Plasma Biomarkers of systemic inflammation and endothelial activation are associated with ED delirium duration in older ED patients without dementia.


Assuntos
Coagulação Sanguínea , Lesões Encefálicas/complicações , Delírio/sangue , Delírio/diagnóstico , Hospitalização , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Barreira Hematoencefálica/lesões , Estudos de Coortes , Delírio/complicações , Delírio/fisiopatologia , Feminino , Humanos , Inflamação/complicações , Masculino , Prognóstico , Fatores de Tempo
18.
Eur Rev Med Pharmacol Sci ; 23(20): 8788-8794, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31696465

RESUMO

OBJECTIVE: To explore the role of long noncoding ribonucleic acid (lncRNA) KCNQ1OT1 in the proliferation, apoptosis, and migration of ovarian cancer cells via Wnt/ß-catenin. MATERIALS AND METHODS: Ovarian cancer A2780 cells were divided into three groups, namely control group, KCNQ1OT1 overexpression group, and KCNQ1OT1 knockdown group. Next, the effect of KCNQ1OT1 on the proliferation of ovarian cancer A2780 cells was detected by cell counting kit-8 (CCK-8) assay. Wound healing assay and transwell assay were carried out to determine the influence of KCNQ1OT1 on the migration ability of ovarian cancer A2780 cells. The role of KCNQ1OT1 in the cell cycle of ovarian cancer A2780 cells was detected via flow cytometry. The impact of KCNQ1OT1 on the expression level of ß-catenin protein in ovarian cancer A2780 cells was determined through Western blotting and fluorescence immunoassay. RESULTS: The proliferation rate of cells was overtly decreased in KCNQ1OT1 knockdown group but significantly increased in KCNQ1OT1 overexpression group. The results of both wound healing and transwell assays showed that the migration ability of cells was reduced in KCNQ1OT1 knockdown group but raised in KCNQ1OT1 overexpression group. According to flow cytometry, the cell cycle was clearly arrested in the G0/G1 phase in KCNQ1OT1 knockdown group. The results of Western blotting and fluorescence immunoassay revealed that compared with that in control group, the expression level of ß-catenin protein evidently declined in KCNQ1OT1 knockdown group, but it was notably elevated in KCNQ1OT1 overexpression group. CONCLUSIONS: Increased lncRNA KCNQ1OT1 in ovarian cancer cells promotes the expression of ß-catenin, thereby facilitating the proliferation and migration of ovarian cancer cells.

19.
J Psychosom Res ; 127: 109850, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31678811

RESUMO

OBJECTIVE: Delirium is acute disorder of attention and cognition. We conducted an observational study using a hospital-wide database to validate three delirium prediction models that were developed to predict prevalent delirium within the first day of hospitalization after ED visit. METHODS: This was a retrospective cohort study at the academic medical center to evaluate the predictive ability of three previously developed prediction models for delirium from 2014 to 2017. We included patients aged 65 years and older who were hospitalized from ED. Nurses used the Delirium Observation Screening Scale (DOSS) twice daily while hospitalized. We extracted variables to examine the three prediction models with a positive DOSS screen within the first day of admission. The predictive ability was summarized using the area under the curve (AUC). RESULTS: We identified 2582 visits with a positive DOSS screen and 877 visits with a diagnosis of delirium from ICD9/10 codes among 12,082 encounters. The AUC of these prediction models ranged from 0.71 to 0.80 when predicting a positive DOSS screen, and 0.68 to 0.72 when predicting a ICD9/10 diagnosis of delirium. In our cohort, the delirium risk score which uses the cutoff of positive or negative predicted DOSS positive delirium with the AUC of 0.8 (p < .0001). The model demonstrated the sensitivity and the specificity of 91.2 (95% CI 90.0-92.3) and 50.3 (95% CI 49.3-51.3). CONCLUSION: In this study, the delirium risk score had the highest predictive ability for prevalent delirium defined by a positive DOSS within the first day of hospitalization.

20.
West J Emerg Med ; 20(6): 926-930, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31738720

RESUMO

INTRODUCTION: Approximately 16% of acutely ill older adults develop new, long-term cognitive impairment (LTCI), many of whom initially seek care in the emergency department (ED). Currently, no effective interventions exist to prevent LTCI after an acute illness. Identifying early and modifiable risk factors for LTCI is the first step toward effective therapy. We hypothesized that Vitamin D deficiency at ED presentation was associated with LTCI in older adults. METHODS: This was an observational analysis of a prospective cohort study that enrolled ED patients ≥ 65 years old who were admitted to the hospital for an acute illness. All patients were enrolled within four hours of ED presentation. Serum Vitamin D was measured at enrollment and Vitamin D deficiency was defined as serum concentrations <20 mg/dL. We measured pre-illness and six-month cognition using the short form Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), which ranges from 1 to 5 (severe cognitive impairment). Multiple linear regression was performed to determine whether Vitamin D deficiency was associated with poorer six-month cognition adjusted for pre-illness IQCODE and other confounders. We incorporated a two-factor interaction into the regression model to determine whether the relationship between Vitamin D deficiency and six-month cognition was modified by pre-illness cognition. RESULTS: We included a total of 134 older ED patients; the median (interquartile range [IQR]) age was 74 (69, 81) years old, 61 (46%) were female, and 14 (10%) were nonwhite race. The median (IQR) vitamin D level at enrollment was 25 (18, 33) milligrams per deciliter and 41 (31%) of enrolled patients met criteria for vitamin D deficiency. Seventy-seven patients survived and had a six-month IQCODE. In patients with intact pre-illness cognition (IQCODE of 3.13), Vitamin D deficiency was significantly associated with worsening six-month cognition (ß-coefficient: 0.43, 95% CI, 0.07 to 0.78, p = 0.02) after adjusting for pre-illness IQCODE and other confounders. Among patients with pre-illness dementia (IQCODE of 4.31), no association with Vitamin D deficiency was observed (ß-coefficient: -0.1;, 95% CI, [-0.50-0.27], p = 0.56). CONCLUSION: Vitamin D deficiency was associated with poorer six-month cognition in acutely ill older adult ED patients who were cognitively intact at baseline. Future studies should determine whether early Vitamin D repletion in the ED improves cognitive outcomes in acutely ill older patients.

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