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[PMID]: 29524917
[Au] Autor:Cardona M; Lewis ET; Turner RM; Alkhouri H; Asha S; Mackenzie J; Perkins M; Suri S; Holdgate A; Winoto L; Chang CW; Gallego-Luxan B; McCarthy S; Kristensen MR; O'Sullivan M; Skjøt-Arkil H; Ekmann AA; Nygaard HH; Jensen JJ; Jensen RO; Pedersen JL; Breen D; Petersen JA; Jensen BN; Mogensen CB; Hillman K; Brabrand M
[Ad] Address:The Simpson Centre for Health Services Research, South Western Sydney Clinical School, The University of New South Wales, PO Box 6087, UNSW, NSW, 1466 Australia. Electronic address: magnolia.cardona@unsw.edu.au.
[Ti] Title:Efficacy of a tool to predict short-term mortality in older people presenting at emergency departments: Protocol for a multi-centre cohort study.
[So] Source:Arch Gerontol Geriatr;76:169-174, 2018 Mar 06.
[Is] ISSN:1872-6976
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Prognostic uncertainty inhibits clinicians from initiating timely end-of-life discussions and advance care planning. This study evaluates the efficacy of the CriSTAL (Criteria for Screening and Triaging to Appropriate aLternative care) checklist in emergency departments. METHODS: Prospective cohort study of patients aged ≥65 years with any diagnosis admitted via emergency departments in ten hospitals in Australia, Denmark and Ireland. Electronic and paper clinical records will be used to extract risk factors such as nursing home residency, physiological deterioration warranting a rapid response call, personal history of active chronic disease, history of hospitalisations or intensive care unit admission in the past year, evidence of proteinuria or ECG abnormalities, and evidence of frailty to be concurrently measured with Fried Score and Clinical Frailty Scale. Patients or their informal caregivers will be contacted by telephone around three months after initial assessment to ascertain survival, self-reported health, post-discharge frailty and health service utilisation since discharge. Logistic regression and bootstrapping techniques and AUROC curves will be used to test the predictive accuracy of CriSTAL for death within 90 days of admission and in-hospital death. DISCUSSION: The CriSTAL checklist is an objective and practical tool for use in emergency departments among older patients to determine individual probability of death in the short-term. Its validation in this cohort is expected to reduce clinicians' prognostic uncertainty on the time to patients' death and encourage timely end-of-life conversations to support clinical decisions with older frail patients and their families about their imminent or future care choices.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524916
[Au] Autor:Lopes H; Mateus C; Rosati N
[Ad] Address:Escola Nacional de Saúde Pública, Universidade NOVA de Lisboa, Lisbon, Portugal. Electronic address: h.lopes@ensp.unl.pt.
[Ti] Title:Impact of long term care and mortality risk in community care and nursing homes populations.
[So] Source:Arch Gerontol Geriatr;76:160-168, 2018 Feb 20.
[Is] ISSN:1872-6976
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:OBJECTIVES: To identify the survival time, the mortality risk factors and the individuals' characteristics associated with cognitive and physical status at discharge, among the Portuguese long-term care (LTC) populations. SETTINGS: Home-and-Community-Based Services (HCBS) and three types of Nursing Homes (NH). PARTICIPANTS: 20,984 individuals admitted and discharged in 2015. MEASUREMENTS: The Kaplan-Meier survival analysis and the Cox Proportional Hazards Models were used to study the mortality risk; the Wilcoxon signed-rank test to identify the number of individuals with cognitive and physical changes between admission and discharge; two cumulative odds ordinal logistic regressions to predict the cognitive and physical dependence levels at discharge RESULTS: The mortality rate at HCBS was 30%, and 17% at the NH, with a median survival time of 173 and 200 days, respectively. The main factors associated with higher mortality were older age, male gender, family/neighbour support, neoplasms and cognitive/physical dependence at admission. In NH/HCBS, 26%/18% of individuals improve their cognitive status, while in physical status the proportion was 38%/27%, respectively. Finally, older age, being illiterate and being classified at the lowest cognitive and physical status at admission decrease the likelihood of achieving a higher level of cognitive and physical independence at discharge. CONCLUSIONS: The adoption of a robust and complete assessment tool, the definition of guidelines to enable a periodical assessment of individuals' autonomy and the adoption of benchmark metrics allowing the comparison of results between similar units are some of the main goals to be taken into account for future developments of this care in Portugal.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524815
[Au] Autor:Sharma D; Singh MP; Vimal D; Kumar S; Jha RR; Chowdhuri DK
[Ad] Address:Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow, 226 001 Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India.
[Ti] Title:Benzene induced resistance in exposed Drosophila melanogaster: Outcome of improved detoxification and gene modulation.
[So] Source:Chemosphere;201:144-158, 2018 Feb 23.
[Is] ISSN:1879-1298
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Adaptive behaviour of an organism has relevance towards developing better resistance in subsequent generations following xenobiotic exposures. Using a genetically tractable and functional insect model, Drosophila melanogaster, we aimed to examine the resistance of the organism against repeated exposures of benzene, an industrial and environmental-chemical and a class I human carcinogen. While 100 mM benzene exposure to one-day old flies for seven days caused ∼95% mortality (F0), its exposure to subsequent generations of flies led a significant decrease in mortality with maximum survival (∼85%) as evident at F28 generation. While burden of benzene and its toxic metabolites was higher in initial generations, in latter generations (F24-F28), concentrations of less toxic metabolites were higher. In parallel, improved metabolism, less oxidative stress, less induction of hsp60 and hsp70 and higher induction of hsp26 and hsp27 along with increased gene dose ratio of three genes (cyp6g1, mrp1, and cyp12d1) were observed in latter generations of benzene exposed flies with maximum benefit accrued in F28 generation. The resistance developed in flies of F28 generation had a negative impact on reproduction which might be due to a cost against selection. The study demonstrates development of benzene resistance in Drosophila with permanent genetic changes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524801
[Au] Autor:Rossini Oliva S; Mingorance MD; Sanhueza D; Fry SC; Leidi EO
[Ad] Address:Department of Plant Biology and Ecology, University of Seville, Av Reina Mercedes, POB 1095, 41080 Seville, Spain.
[Ti] Title:Active proton efflux, nutrient retention and boron-bridging of pectin are related to greater tolerance of proton toxicity in the roots of two Erica species.
[So] Source:Plant Physiol Biochem;126:142-151, 2018 Mar 02.
[Is] ISSN:1873-2690
[Cp] Country of publication:France
[La] Language:eng
[Ab] Abstract:BACKGROUND AND AIMS: Tolerance to soil acidity was studied in two species of Ericaceae that grow in mine-contaminated soils (S Portugal, SW Spain) to find out if there are interspecific variations in H tolerance which might be related to their particular location. METHODS: Tolerance to H toxicity was tested in nutrient solutions using seeds collected in SW Spain. Plant growth and nutrient contents in leaves, stems and roots were determined. Viability tests and proton exchange were studied in roots exposed, short-term, to acidic conditions. Membrane ATPase activity and the cell-wall pectic polysaccharide domain rhamnogalacturonan-II (RG-II) were analysed to find out interspecific differences. RESULTS: Variation in survival, growth and mineral composition was found between species. The H -tolerant species (Erica andevalensis) showed greater concentration of nutrients than E. australis. Very low pH (pH 2) produced a significant loss of root nutrients (K, P, Mg) in the sensitive species. Root ATPase activity was slightly higher in the tolerant species with a correspondingly greater H efflux capacity. In both species, the great majority of the RG-II domains were in their boron-bridged dimeric form. However, shifting to a medium of pH 2 caused some of the boron bridges to break in the sensitive species. CONCLUSIONS: Variation in elements linked to the cell wall-membrane complex and the stability of their components (RG-II, H -ATPases) are crucial for acid stress tolerance. Thus, by maintaining root cell structure, active proton efflux avoided toxic H build-up in the cytoplasm and supported greater nutrient acquisition in H -tolerant species.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524739
[Au] Autor:Medeiros BC
[Ad] Address:Department of Medicine, Stanford University School of Medicine, 875 Blake Wilbur Dr, Stanford, CA, USA. Electronic address: brunom@stanford.edu.
[Ti] Title:Interpretation of clinical endpoints in trials of acute myeloid leukemia.
[So] Source:Leuk Res;68:32-39, 2018 Feb 07.
[Is] ISSN:1873-5835
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Treatment regimens for acute myeloid leukemia (AML) have remained largely unchanged until recently. Molecular advances have opened the door to targeted therapies, many of which are in late-phase clinical trials. As new therapeutic opportunities arise, it is appropriate to review key aspects of clinical trial design, statistical interpretation of outcomes, and methods of data reporting. Complete remission and overall survival (OS) are common primary endpoints in early-phase AML clinical trials. OS and event-free survival are frequent primary endpoints in phase 3 trials. Clinical trials are designed to address the primary endpoint using prespecified α and power levels. Interpretation of additional endpoints (eg, secondary endpoints and subgroup analyses) must be viewed in light of a trial's statistical design. Furthermore, variations in reporting of endpoints must be considered in order to understand trial outcomes. Time-to-event endpoints are typically reported using Kaplan-Meier curves, which are visually informative. Statistical data derived from these curves can be complex, and a variety of factors may impact interpretation. The purpose of this review is to discuss the nuances of common AML trial endpoints and their data presentation to better inform evaluation and understanding of clinical trial data.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524717
[Au] Autor:Wang T; Gao T; Niu X; Xing X; Yang Y; Liu Y; Mao Q
[Ad] Address:Department of Neurosurgery, West China Hospital, Sichuan University, Guoxue Alley 37, Chengdu, 610041, China; Department of Neurosurgery, Xi'an Central Hospital, Xi'an, China.
[Ti] Title:Clinical Characteristics and Prognostic Analysis of Glioma with HIV Patients.
[So] Source:World Neurosurg;, 2018 Mar 07.
[Is] ISSN:1878-8769
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: The aim of this study was to perform an survival analysis of HIV patients with glioma and to assess the relationship between various prognostic factors and overall survival. METHODS: We reported in detail the management and prognosis of two patients in our hospital and performed a quantitative and comprehensive systematic literature review of patients with HIV-associated glioma. We combined our treatment experience with retrospectively obtained treatment information and studied the resultant survival time to statistically analyze and discuss whether age, surgery, gender, WHO grade, radiotherapy, chemotherapy and RT combined CTh could predict patients' survival. RESULT: We included 34 cases in our study, including two of our cases. The median survival was 9 months. On survival analysis, among the aforementioned parameters, WHO grade(LGG/HGG), surgery(SR/SB) and radiotherapy showed significant association with overall survival by univariate analysis. Multivariable analysis showed WHO grade and surgery were a significant predictor of OS. CONCLUSION: Most patients had astrocytoma or high-grade glioma. The median survival of all of glioma in HIV patients was shorter than that of GBM patients. Surgery and WHO grade were independent prognostic factors for overall survival.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524653
[Au] Autor:Zhang JM; López-Pujol J; Gong X; Wang HF; Vilatersana R; Zhou SL
[Ad] Address:State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Nanxincun 20, Xiangshan, 100093 Beijing, China; National Genebank, Institute of Crop Science (ICS), Chinese Academy of Agricultural Sciences (CAAS), Nan Dajie 12, Zhongguancun, Beijing 10008
[Ti] Title:Population genetic dynamics of Himalayan-Hengduan tree peonies, Paeonia subsect. Delavayanae.
[So] Source:Mol Phylogenet Evol;, 2018 Mar 07.
[Is] ISSN:1095-9513
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:According to the present taxonomical treatment, Paeonia subsect. Delavayanae consists of only two species (P. delavayi and P. ludlowii) endemic to the Himalayan-Hengduan Mountains. Although P. ludlowii can be distinguished from P. delavayi on the basis of a series of morphological characters, the species delimitation remains controversial because the more widespread one, P. delavayi, exhibits considerable morphological diversity. Both chloroplast DNA markers and nuclear microsatellites or simple sequence repeats (nSSR) are used herein to reveal genetic diversity and relationships of the two taxa included in this subsection, and ecological niche modeling (ENM) is employed to get insights into their paleodistribution. Our results show that genetic boundaries between the two currently recognized species are unclear, probably due to recent divergence. Paeonia ludlowii is budding from P. delavayi, probably by genetic isolation but also by shifting its niche to the harsher upland Tibetan conditions. Paeonia delavayi itself would be, however, under active speciation, showing significant genetic differentiation and morphological diversity. Whereas P. ludlowii would have endured the Pleistocene glacial periods by in situ persistence in local, small refugia, a 'dual' model seems to apply for P. delavayi (in situ persistence and retreat to refugia). The rarity of P. ludlowii and high evolutionary potential of P. delavayi imply high priority of in situ conservation of both taxa. The Himalayan-Hengduan Mountains are an ideal arena for differentiation within subsect. Delavayanae of Paeonia, by means of expansions/contractions/displacements, vertical migration, and local survival/extinctions in response to the Neogene climate fluctuations and geological changes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524631
[Au] Autor:Wang H; Sun W; Sun M; Fu Z; Zhou C; Wang C; Zuo D; Zhou Z; Wang G; Zhang T; Xu J; Chen J; Wang Z; Yin F; Duan Z; Hornicek FJ; Cai Z; Hua Y
[Ad] Address:Department of Orthopedics, Shanghai General Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China; Department of Orthopedics, Yangpu Hospital, Tongji University, Shanghai, China.
[Ti] Title:HER4 promotes cell survival and chemoresistance in osteosarcoma via interaction with NDRG1.
[So] Source:Biochim Biophys Acta;, 2018 Mar 07.
[Is] ISSN:0006-3002
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. The abilities of chemotherapy resistance are major roadblock in the successful treatment of OS. The clarification of mechanism regarding cell survival during OS chemotherapy are important. Here, we examined HER4 expression by immunohistochemistry in a large series of OS tissues, and found HER4 expression correlated with tumor characteristics and patient survival rates. HER4 knockdown by shRNA inhibited OS cell growth and tumorigenesis, and induced cell senescence and apoptosis in vitro and in vivo. We demonstrated that HER4 expression upregulated in the adverse conditions, such as serum starvation and sphere culture. Moreover, HER4 knockdown cells became more sensitive in stressful conditions such as loss of attachment, cytotoxic agents or nutrition insufficiency. Mechanism studies revealed that HER4 interacted with NDRG1, and NDRG1 overexpression could antagonize HER4 knockdown-mediated cell growth and apoptosis in stressed conditions. There was a positive correlation between HER4 and NDRG1 immunoreactivity in OS patients. Together, our present study shows that HER4 and/or NDRG might play a critical role for the cell survival and chemo-resistance of OS, and could be used as potential therapeutic targets in OS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524627
[Au] Autor:Matschke LA; Rinné S; Snutch TP; Oertel WH; Dolga AM; Decher N
[Ad] Address:Institute for Physiology and Pathophysiology, Vegetative Physiology and Marburg Center for Mind, Brain and Behavior - MCMBB, Philipps-University Marburg, 35037 Marburg, Germany; Clinic for Neurology, Philipps-University Marburg, 35037 Marburg, Germany. Electronic address: lina.matschke@staff.uni-mar
[Ti] Title:Calcium-activated SK potassium channels are key modulators of the pacemaker frequency in locus coeruleus neurons.
[So] Source:Mol Cell Neurosci;, 2018 Mar 07.
[Is] ISSN:1095-9327
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The physiological, intrinsic activity of noradrenergic locus coeruleus (LC) neurons is important for the control of sleep/wakefulness, cognition and autonomous body functions. Dysregulations of the LC-noradrenergic network contribute to the pathogenesis of psychiatric disorders and are key findings in early stages of neurodegenerative diseases. Therefore, identifying ion channels mediating the intrinsic pacemaking mechanism of LC neurons, which is in turn directly coupled to Ca homeostasis and cell survival signaling pathways, can help to foster our understanding of the vulnerability of these neurons in neurodegenerative diseases. Small-conductance Ca -activated K (SK) channels regulate the intrinsic firing patterns in different central neurons and are essential regulators of the intracellular Ca homeostasis. However, the role of SK channels for the intrinsic pacemaking of LC neurons in mice is still unclear. Therefore we performed qPCR expression analysis as well as patch clamp recordings of in vitro brainstem slices, for instance testing SK channel blockers and activators like apamin and NS309, respectively. Although we found a transcriptional expression of SK1, SK2 and SK3 channels, SK2 was the predominantly expressed subunit in mouse LC neurons. Using perforated-patch clamp experiments, we found that SK channels are essential regulators of the intrinsic pacemaking of LC neurons, mediating a large fraction of the afterhyperpolarization (AHP) in these cells. Consistent with previous observations that a concerted action of L- and T-type Cav channels is essential for the pacemaking of LC neurons, we found that SK channel activation, and the respective AHP amplitude, is primarily coupled to Ca influx via these types of Ca channels. Our study identified SK2 channels as drug targets for the tuning of the pacemaker frequency in disorders involving a dysregulation of the LC.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524556
[Au] Autor:Li W; Qiu T; Guo L; Ling Y; Gao Y; Ying J; He J
[Ad] Address:Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
[Ti] Title:Primary and acquired EGFR T790M-mutant NSCLC patients identified by routine mutation testing show different characteristics but may both respond to osimertinib treatment.
[So] Source:Cancer Lett;, 2018 Mar 07.
[Is] ISSN:1872-7980
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:Primary EGFR T790M mutation is occasionally identified by routine mutation testing in tyrosine kinase inhibitor (TKI)-naive patients with non-small cell lung cancer (NSCLC). We herein aimed to compare the characteristics of primary and acquired T790M mutations in NSCLC patients, and their response to osimertinib. Using amplification refractory mutation system (ARMS) detection, primary T790M was identified in 0.5% (46/8723) of TKI-naive patients, whereas acquired T790M was detected in 49.7% (71/143) of TKI-relapsed patients. T790M always coexisted with a sensitizing EGFR mutation. Primary T790M more commonly coexisted with L858R, whereas acquired T790M was more likely to coexist with exon 19 deletions. Moreover, next-generation sequencing (NGS) showed that concomitant sensitizing EGFR and primary T790M mutant allele frequencies (MAFs) were highly concordant, but acquired T790M MAFs were significantly lower than the sensitizing EGFR MAFs. Sixteen acquired T790M-mutant patients received osimertinib. The median progression-free survival (PFS) was 8.1 months. Four primary T790M-mutant patients received osimertinib and the median PFS was 8.0 months. Together, our study demonstrates that primary and acquired T790M-mutant patients show distinct differences in some clinical and molecular characteristics, but may both respond to osimertinib treatment.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher


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