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Sample records for patients starting pd

  1. 18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start

    Energy Technology Data Exchange (ETDEWEB)

    Seith, Ferdinand; Schmidt, Holger; Pfannenberg, Christina; Gueckel, Brigitte; Schwenzer, Nina [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Forschner, Andrea; Garbe, Claus [Eberhard Karls University, Department of Dermatology, Tuebingen (Germany); Nikolaou, Konstantin [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); German Cancer Consortium (DKTK), Heidelberg (Germany); La Fougere, Christian [German Cancer Consortium (DKTK), Heidelberg (Germany); Eberhard Karls University, Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Tuebingen (Germany)

    2018-01-15

    The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation. Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t{sub 0}, base-line), two weeks (t{sub 1}, study examination) and three months after treatment initiation (t{sub 2}, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients. Three patients with partial metabolic response in PET at t{sub 1} turned out to have complete response at t{sub 2}. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t{sub 2}, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t{sub 1}. OS in patients with PMD at t{sub 2} varied between 148 and 814 days. SMD at both t{sub 1} and t{sub 2} was seen in one patient, tumor progress was observed after 308 days. Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future. (orig.)

  2. Unplanned Start on Peritoneal Dialysis Right after PD Catheter Implantation for Older People with End-Stage Renal Disease.

    Science.gov (United States)

    Povlsen, Johan V; Sørensen, Anette Bagger; Ivarsen, Per

    2015-11-01

    Unplanned start on dialysis remains a major problem for the dialysis community worldwide. Late-referred patients with end-stage renal disease (ESRD) and urgent need for dialysis are overrepresented among older people. These patients are particularly likely to be started on in-center hemodialysis (HD), with a temporary vascular access known to be associated with excess mortality and increased risks of potentially lethal complications such as bacteremia and central venous thrombosis or stenosis.The present paper describes in detail our program for unplanned start on automated peritoneal dialysis (APD) right after PD catheter implantation and summarizes our experiences with the program so far. Compared with planned start on PD after at least 2 weeks of break-in between PD catheter implantation and initiation of dialysis, unplanned start may be associated with a slight increased risk of mechanical complications but apparently no detrimental effect on mortality, peritonitis-free survival, or PD technique survival.In our opinion and experience, the risk of serious complications associated with the implantation and immediate use of a PD catheter is less than the risk of complications associated with unplanned start on HD with a temporary central venous catheter (CVC). Unplanned start on APD is a gentle, safe, and feasible alternative to unplanned start on HD with a temporary CVC that is also valid for the late-referred older patient with ESRD and urgent need for dialysis. Copyright © 2015 International Society for Peritoneal Dialysis.

  3. Empowering Patients: PD in Healthcare

    DEFF Research Database (Denmark)

    Kensing, Finn; Strand, Dixi Louise; Bansler, Jørgen P.

    2004-01-01

    In this paper, we discuss PD issues and concerns in the context of a national initiative the purpose of which is to provide IT support for the communication and collaboration within a heterogeneous network of patients/citizens and health care professionals. We present the notion of patient empowe...

  4. Comparison of outcomes between emergent-start and planned-start peritoneal dialysis in incident ESRD patients: a prospective observational study.

    Science.gov (United States)

    Li, Wen-Yi; Wang, Yi-Cheng; Hwang, Shang-Jyh; Lin, Shih-Hua; Wu, Kwan-Dun; Chen, Yung-Ming

    2017-12-11

    The clinical consequences of starting chronic peritoneal dialysis (PD) after emergent dialysis via a temporary hemodialysis (HD) catheter has rarely been evaluated within a full spectrum of treated end-stage renal disease (ESRD). We investigated the longer-term outcomes of patients undergoing emergent-start PD in comparison with that of other practices of PD or HD in a prospective cohort of new-onset ESRD. This was a 2-year prospective observational study. We enrolled 507 incident ESRD patients, among them 111 chose PD (43 planned-start, 68 emergent-start) and 396 chose HD (116 planned-start, 280 emergent-start) as the long-term dialysis modality. The logistic regression model was used to identify variables associated with emergent-start dialysis. The Kaplan-Meier survival analysis was used to determine patient survival and technique failure. The propensity score-adjusted Cox regression model was used to identify factors associated with patient outcomes. During the 2-year follow-up, we observed 5 (4.5%) deaths, 15 (13.5%) death-censored technique failures (transfer to HD) and 3 (2.7%) renal transplantations occurring in the PD population. Lack of predialysis education, lower predialysis estimated glomerular filtration rate and serum albumin were predictors of being assigned to emergent dialysis initiation. The emergent starters of PD displayed similar risks of patient survival, technique failure and overall hospitalization, compared with the planned-start counterparts. By contrast, the concurrent planned-start and emergent-start HD patients with an arteriovenous fistula or graft were protected from early overall death and access infection-related mortality, compared with the emergent HD starters using a central venous catheter. In late-referred chronic kidney disease patients who have initiated emergent dialysis via a temporary HD catheter, post-initiation PD can be a safe and effective long-term treatment option. Nevertheless, due to the potential complications

  5. Offering Patients Therapy Options in Unplanned Start (OPTiONS)

    DEFF Research Database (Denmark)

    Machowska, Anna; Alscher, Mark Dominik; Vanga, Satyanarayana Reddy

    2017-01-01

    -EP. Among 177 patients who chose dialysis modality after UPS-EP, 103 (58%) chose PD (but only 86% of them received PD) and 74 (42%) chose HD (95% received HD). Logistic regression analysis showed that diabetes 1.88 (1.05 - 3.37) and receiving UPS-EP, OR = 4.74 (CI, 2.05 - 10.98) predicted receipt of PD...... pathways and enabling informed choice of dialysis modality was implemented. We here report on impact of UPS-EP on modality choice and clinical outcomes in UPS patients. Methods: This non-interventional, prospective, multi-center, observational study included 270 UPS patients from 26 centers in 6 European....... Peritonitis and bacteraemia rates were better than international guideline standards. Conclusions: UPS-EP predicted patient use of PD but 14% of those choosing PD after UPS-EP still did not receive the modality they preferred. Patient survival in patients choosing and/or receiving PD was similar to HD despite...

  6. Factors determining when to start levodopa/carbidopa/entacapone treatment in Spanish patients with Parkinson's disease.

    Science.gov (United States)

    Martínez-Martín, P; Hernández, B; Ricart, J

    2014-04-01

    Several therapeutic options are available for the symptomatic treatment of Parkinson's disease (PD).There is no reliable information about which factors are involved in the choice of treatment. To identify factors contributing to the decision to start treatment with levodopa/carbidopa/entacapone (LCE) in patients with PD. We completed a descriptive cross-sectional retrospective multicentre study of patients with idiopathic PD receiving LCE. Clinical data were collected with special attention to factors that could potentially determine when to initiate treatment with LCE in normal clinical practice. We studied 1050 patients with a mean age of 71.3±8.7 years (58.2% men). Average time from onset of symptoms to diagnosis was 13.8±12.9 months, with a latency time of 74.5±53.6 months before starting LCE treatment. The most common initial symptoms were tremor (70.6%), reduced dexterity (43.2%) and slowness of movement (41.5%). At the start of LCE treatment, most patients were in Hoehn and Yahr stage 2 (57.5%), with an average rating of 73.4% on the Schwab & England scale. Eight hundred twenty two patients (78.3%) received treatment with other drugs before starting LCE (mean time between starting any PD treatment and starting LCE was 40.5±47.2 months). Clinical factors with a moderate, marked, or crucial effect on the decision to start LCE treatment were bradykinesia (84.7%), daytime rigidity (72.2%), general decline (72.2%), difficulty walking (66.4%), tremor (62.7%), nocturnal rigidity (56.1%), and postural instability (53%). Difficulty performing activities of daily living was the only psychosocial factor identified as having an influence on the decision (84.3%). The decision to start patients with idiopathic PD on LCE treatment is mainly determined by motor deficits and disabilities associated with disease progression. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  7. Feasibility of Urgent-Start Peritoneal Dialysis in Older Patients with End-Stage Renal Disease: A Single-Center Experience.

    Science.gov (United States)

    Jin, Haijiao; Ni, Zhaohui; Mou, Shan; Lu, Renhua; Fang, Wei; Huang, Jiaying; Hu, Chunhua; Zhang, Haifen; Yan, Hao; Li, Zhenyuan; Yu, Zanzhe

    2018-01-01

    Patients with end-stage renal disease (ESRD) frequently require urgent-start dialysis. Recent evidence suggests that peritoneal dialysis (PD) might be a feasible alternative to hemodialysis (HD) in these patients, including in older patients. This retrospective study enrolled patients aged > 65 years with ESRD who underwent urgent dialysis without functional vascular access or PD catheter at a single center, from January 2011 to December 2014. Patients were grouped based on their dialysis modality (PD or HD). Patients unable to tolerate PD catheter insertion or wait for PD were excluded. Each patient was followed for at least 30 days after catheter insertion. Short-term (30-day) dialysis-related complications and patient survival were compared between the 2 groups. A total of 94 patients were enrolled, including 53 (56.4%) who underwent PD. The incidence of dialysis-related complications during the first 30 days was significantly lower in PD compared with HD patients (3 [5.7%] vs 10 [24.4%], p = 0.009). Logistic regression identified urgent-start HD as an independent risk factor for dialysis-related complications compared with urgent-start PD (odds ratio 4.760 [1.183 - 19.147], p = 0.028). The 6-, 12-, 24-, and 36-month survival rates in the PD and HD groups were 92.3% vs 94.6%, 82.4% vs 81.3%, 75.7% vs 74.2%, and 69.5% vs 60.6%, respectively, with no significant differences between the groups (log-rank = 0.011, p = 0.915). Urgent-start PD was associated with fewer short-term dialysis-related complications and similar survival to urgent-start HD in older patients with ESRD. Peritoneal dialysis may thus be a safe and effective dialysis modality for older ESRD patients requiring urgent dialysis. Copyright © 2018 International Society for Peritoneal Dialysis.

  8. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in patients ...

    African Journals Online (AJOL)

    This is a study of Glucose-6-phosphate dehydrogenase(G6PD) deficiency in sickle cell anaemia patients attending the haematology clinic of the Jos University Teaching Hospital (JUTH), Jos- Nigeria. The prevalence of G6PD deficiency among the 130 sickle cell anaemia patients studied was found to be 18.5%. G6PD ...

  9. THE CHALLENGE OF PD PATIENTS: GLUCOSE AND GLUCOSE DEGRADATION PRODUCTS IN PD SOLUTION

    Directory of Open Access Journals (Sweden)

    Yong-Lim Kim

    2012-06-01

    Full Text Available The main osmotic agent found in the peritoneal dialysis (PD solution is glucose. It has been of a wide use for great crystalloid osmotic power at a low concentration, simple metabolism, and excellent safety. On the other hand, anywhere between 60 to 80% of the glucose in the PD solution is absorbed - a 100 to 300 mg of daily glucose absorption. Once into the systemic circulation, glucose can be a cause for metabolic complications including obesity. Indeed, the diabetiform change observed in the peritoneal membrane in the long-term PD patients is believed attributable to the high-concentration glucose in the PD solution. The glucose absorbed from peritoneal cavity raises the risk of ‘glucose toxicity’, leading to insulin resistance and beta cell failure. Clinical similarity can be found in postprandial hyperglycemia, which is known to be associated with oxidative stress, endothelial dysfunction, NF-κb, and inflammation, affecting myocardial blood flow. Moreover, it is a proven independent risk factor of coronary artery disease in patients with type 2 diabetes, particularly of female gender. Though speculative yet, glucose toxicity might explain a higher mortality of PD patients after the first year compared with those on hemodialysis (more so in female, advanced-age patients with diabetes. Also included in the picture are glucose degradation products (GDPs generated along the course of heat sterilization or storage of the PD solution. They have been shown to induce apoptosis of peritoneal mesothelial cells, renal tubular epithelial cells, and endothelial cells, while spurring production of TGF-β and VEGF and facilitating epithelial mesenchymal transition. GDPs provide a stronger reactivity than glucose in the formation of AGEs, a known cause for microvascular complications and arteriosclerosis. Unfortunately, clinical studies using a low-GDP PD solution have provided mixed results on the residual renal function, peritonitis, peritoneal

  10. Dialysis access, infections, and hospitalisations in unplanned dialysis start patients

    DEFF Research Database (Denmark)

    Machowska, Anna; Alscher, Mark Dominik; Vanga, Satyanarayana Reddy

    2017-01-01

    Introduction: Unplanned dialysis start (UPS) associates with worse clinical outcomes, higher utilisation of healthcare resources, lower chances to select dialysis modality and UPS patients typically commenced in-centre haemodialysis (HD) with central venous catheter (CVC). We evaluated patient ou...

  11. Cardiovascular and noncardiovascular mortality among patients starting dialysis

    DEFF Research Database (Denmark)

    de Jager, Dinanda J; Grootendorst, Diana C; Jager, Kitty J

    2009-01-01

    CONTEXT: Cardiovascular mortality is considered the main cause of death in patients receiving dialysis and is 10 to 20 times higher in such patients than in the general population. OBJECTIVE: To evaluate if high overall mortality in patients starting dialysis is a consequence of increased cardiov...

  12. Patient perspectives on the optimal start of renal replacement therapy.

    Science.gov (United States)

    Henry, Shayna L; Munoz-Plaza, Corrine; Garcia Delgadillo, Jazmine; Mihara, Nichole K; Rutkowski, Mark P

    2017-09-01

    Healthcare systems and providers are encouraged to prepare their patients with advanced chronic kidney disease (CKD) for a planned start to renal replacement therapies (RRT). Less well understood are the socioemotional experiences surrounding the optimal start of RRT versus suboptimal haemodialysis (HD) starts with a central catheter. To characterise the experiences of patients beginning RRT. Qualitative, semi-structured phone interviews. A total of 168 patients with stage 5 CKD initiating RRT in an integrated, capitated learning healthcare system. Qualitative data from patients were collected as part of a quality improvement initiative to better understand patient-reported themes concerning preparation for RRT, patients' perceptions of their transition to dialysis and why sub-optimal starts for RRT occur within our healthcare system. Dual review and verification was used to identify key phrases and themes within and across each domain, using both deductive a priori codes generated by the interview guide and grounded discovery of emergent themes. From the patient perspective, preparing for RRT is an experience rooted in deep feelings of fear. In addition, a number of key factors contributed to patients' preparation (or failure to prepare) for RRT. While the education provided by our system was viewed as adequate overall, patients often felt that their emotional and psychosocial needs went unmet, regardless of whether or not, they experienced an optimal dialysis start. Future efforts should incorporate additional strategies for helping patients with advanced CKD achieve emotional and psychological safety while preparing for RRT. © 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  13. Validation of the quantitative point-of-care CareStart biosensor for assessment of G6PD activity in venous blood.

    Directory of Open Access Journals (Sweden)

    Germana Bancone

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common enzymopathy in the human population affecting an estimated 8% of the world population, especially those living in areas of past and present malaria endemicity. Decreased G6PD enzymatic activity is associated with drug-induced hemolysis and increased risk of severe neonatal hyperbilirubinemia leading to brain damage. The G6PD gene is on the X chromosome therefore mutations cause enzymatic deficiency in hemizygote males and homozygote females while the majority of heterozygous females have an intermediate activity (between 30-80% of normal with a large distribution into the range of deficiency and normality. Current G6PD qualitative tests are unable to diagnose G6PD intermediate activities which could hinder wide use of 8-aminoquinolines for Plasmodium vivax elimination. The aim of the study was to assess the diagnostic performances of the new Carestart G6PD quantitative biosensor.A total of 150 samples of venous blood with G6PD deficient, intermediate and normal phenotypes were collected among healthy volunteers living along the north-western Thailand-Myanmar border. Samples were analyzed by complete blood count, by gold standard spectrophotometric assay using Trinity kits and by the latest model of Carestart G6PD biosensor which analyzes both G6PD and hemoglobin.Bland-Altman comparison of the CareStart normalized G6PD values to that of the gold standard assay showed a strong bias in values resulting in poor area under-the-curve values for both 30% and 80% thresholds. Performing a receiver operator curve identified threshold values for the CareStart product equivalent to the 30% and 80% gold standard values with good sensitivity and specificity values, 100% and 92% (for 30% G6PD activity and 92% and 94% (for 80% activity respectively.The Carestart G6PD biosensor represents a significant improvement for quantitative diagnosis of G6PD deficiency over previous versions. Further

  14. Validation of the quantitative point-of-care CareStart biosensor for assessment of G6PD activity in venous blood.

    Science.gov (United States)

    Bancone, Germana; Gornsawun, Gornpan; Chu, Cindy S; Porn, Pen; Pal, Sampa; Bansil, Pooja; Domingo, Gonzalo J; Nosten, Francois

    2018-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the human population affecting an estimated 8% of the world population, especially those living in areas of past and present malaria endemicity. Decreased G6PD enzymatic activity is associated with drug-induced hemolysis and increased risk of severe neonatal hyperbilirubinemia leading to brain damage. The G6PD gene is on the X chromosome therefore mutations cause enzymatic deficiency in hemizygote males and homozygote females while the majority of heterozygous females have an intermediate activity (between 30-80% of normal) with a large distribution into the range of deficiency and normality. Current G6PD qualitative tests are unable to diagnose G6PD intermediate activities which could hinder wide use of 8-aminoquinolines for Plasmodium vivax elimination. The aim of the study was to assess the diagnostic performances of the new Carestart G6PD quantitative biosensor. A total of 150 samples of venous blood with G6PD deficient, intermediate and normal phenotypes were collected among healthy volunteers living along the north-western Thailand-Myanmar border. Samples were analyzed by complete blood count, by gold standard spectrophotometric assay using Trinity kits and by the latest model of Carestart G6PD biosensor which analyzes both G6PD and hemoglobin. Bland-Altman comparison of the CareStart normalized G6PD values to that of the gold standard assay showed a strong bias in values resulting in poor area under-the-curve values for both 30% and 80% thresholds. Performing a receiver operator curve identified threshold values for the CareStart product equivalent to the 30% and 80% gold standard values with good sensitivity and specificity values, 100% and 92% (for 30% G6PD activity) and 92% and 94% (for 80% activity) respectively. The Carestart G6PD biosensor represents a significant improvement for quantitative diagnosis of G6PD deficiency over previous versions. Further improvements

  15. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment

    DEFF Research Database (Denmark)

    Olsen, Mette Frahm; Abdissa, Alemseged; Kæstel, Pernille

    2014-01-01

    Objectives: To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months....../µL (−2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not significantly different in direct comparison. Exploratory analysis showed that relatively more lean body mass was gained by patients...... with undetectable viral load at three months. Patients receiving delayed supplementation had higher weight gain but lower gains in functional outcomes. Conclusions: Lipid based nutritional supplements improved gain of weight, lean body mass, and grip strength in patients with HIV starting ART. Supplements...

  16. PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients

    DEFF Research Database (Denmark)

    Liu, Yawei; Carlsson, Robert; Ambjørn, Malene

    2013-01-01

    Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. In general, tumor growth requires disruption of the tissue microenvironment, yet how this affects glioma progression is unknown. We studied program death-ligand (PD-L)1 in neurons and gliomas in tumors from GBM patients...... and associated the findings with clinical outcome. Remarkably, we found that upregulation of PD-L1 by neurons in tumor-adjacent brain tissue (TABT) associated positively with GBM patient survival, whereas lack of neuronal PD-L1 expression was associated with high PD-L1 in tumors and unfavorable prognosis...... in GBM patients, better survival in wild-type mice was associated with high neuronal PD-L1 in TABT and downregulation of PD-L1 in tumors, which was defective in Ifnb-/- mice. Our data indicated that neuronal PD-L1 signaling in brain cells was important for GBM patient survival. Reciprocal PD-L1...

  17. Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP): Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis.

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    Birtas Atesoglu, Elif; Tarkun, Pinar; Demirsoy, Esra Terzi; Geduk, Ayfer; Mehtap, Ozgur; Batman, Adnan; Kaya, Fatih; Cekmen, Mustafa Baki; Gulbas, Zafer; Hacıhanefioglu, Abdullah

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP. © The Author(s) 2014.

  18. [Inappropriate prescription in older patients: the STOPP/START criteria].

    LENUS (Irish Health Repository)

    Delgado Silveira, Eva

    2009-09-01

    Older people are a heterogeneous group of patients, often with multiple comorbidities for which they are prescribed a large number of drugs, leading to an increased risk of adverse drug reactions (ADR) and drug interactions. This risk is compounded by physiological age-related changes in physiology, changes in drug pharmacokinetics and pharmacodynamics, as well as by disease-related, functional and social issues. Inappropriate prescription of drugs is common in the older individuals and contributes to the increased risk of ADR. Several tools have been developed to detect potentially inappropriate prescription, the most frequently used in Spain being Beers\\' criteria. However, the value of these criteria is limited, especially as they were developed in a different healthcare system. In this article, the Spanish version of a new tool to detect potentially inappropriate prescriptions-STOPP (Screening Tool of Older Person\\'s Prescriptions) and START (Screening Tool to Alert doctors to Right i.e. appropriate, indicated Treatment) criteria-is presented. The creation, development, reliability, and use of these criteria in routine practice is described and discussed. These criteria have shown better sensitivity than Beers\\' criteria in detecting prescription problems and have the added value of being able to detect not only inappropriate prescription of some drugs, but also the omission of well indicated drugs. The STOPP\\/START criteria could become a useful screening tool to improve prescription in older people.

  19. The clinical research on fractionated irradiation treatment with X knife in patients of PD

    International Nuclear Information System (INIS)

    Wei Pengxiang; Chen Xu; Ai Quanshan; Xia Jiyong; Yang Jiongda; Chen Binghuan

    2003-01-01

    Objective: To explore X knife treatment methods and to seek a new effective way for PD therapy. Methods: Sixteen patients of PD were treated by performing VIM with 2 times of X knife fractionated irradiation (interval, 24 h) to a total dose of 140 Gy, and 8 patients of PD were treated by performing VIM with 3 times of X knife fractionated irradiation (interval, 24 h) to a total of dose of 165 Gy. Results: During 3-24 months follow-up after X knife treatment, tremor was stopped in 19 patients and was relived significantly in 5 patients. Rigidity and bradykinesia of PD were relieved slightly. No complications were observed. Conclusion: To perform VIM with X knife fractionated irradiation can be safely and effectively used to treat PD. The tremor of PD can be relieved slightly

  20. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients

    DEFF Research Database (Denmark)

    Ørskov, Andreas D; Treppendahl, Marianne B; Skovbo, Anni

    2015-01-01

    receptor PD-1 is regulated by DNA methylation. In 12 of 27 patients (44%) PD-1 promoter demethylation was observed in sorted peripheral blood T cells isolated over consecutive cycles of treatment with 5-azacytidine (5-aza). The PD-1 promoter demethylation correlated with an increase in PD-1 expression...... HMA treatment can be a possible resistance mechanism, which may be overcome by combination therapy with a PD-1 pathway inhibitor....

  1. Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Brittany A Goods

    Full Text Available Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1 have been highly successful in the treatment of cancer. While PD-1 expression has been widely investigated, its role in CD4+ effector T cells in the setting of health and cancer remains unclear, particularly in the setting of glioblastoma multiforme (GBM, the most aggressive and common form of brain cancer. We examined the functional and molecular features of PD-1+CD4+CD25-CD127+Foxp3-effector cells in healthy subjects and in patients with GBM. In healthy subjects, we found that PD-1+CD4+ effector cells are dysfunctional: they do not proliferate but can secrete large quantities of IFNγ. Strikingly, blocking antibodies against PD-1 did not rescue proliferation. RNA-sequencing revealed features of exhaustion in PD-1+ CD4 effectors. In the context of GBM, tumors were enriched in PD-1+ CD4+ effectors that were similarly dysfunctional and unable to proliferate. Furthermore, we found enrichment of PD-1+TIM-3+ CD4+ effectors in tumors, suggesting that co-blockade of PD-1 and TIM-3 in GBM may be therapeutically beneficial. RNA-sequencing of blood and tumors from GBM patients revealed distinct differences between CD4+ effectors from both compartments with enrichment in multiple gene sets from tumor infiltrating PD-1-CD4+ effectors cells. Enrichment of these gene sets in tumor suggests a more metabolically active cell state with signaling through other co-receptors. PD-1 expression on CD4 cells identifies a dysfunctional subset refractory to rescue with PD-1 blocking antibodies, suggesting that the influence of immune checkpoint inhibitors may involve recovery of function in the PD-1-CD4+ T cell compartment. Additionally, co-blockade of PD-1 and TIM-3 in GBM may be therapeutically beneficial.

  2. Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

    DEFF Research Database (Denmark)

    Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda

    2018-01-01

    Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unkn...... expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.......Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression...... is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. Materials and methods: We...

  3. Oral supplementation of vitamin E reduces osmotic fragility of RBC in hemolytic anemic patients with G6PD deficiency

    International Nuclear Information System (INIS)

    Sultana, N.; Begum, S.; Begum, N.; Ali, T.

    2009-01-01

    Vitamin E has role in maintaining the integrity of red cell member by preventing oxidation of polyunsaturated fatty acids, thus protects cells from oxidative stress-induced lysis in G6PD deficiency. Changes in osmotic fragility of RBC and some absolute values like MCV, MCH and MCHC may occur in haemolytic anaemic patients with G6PD deficiency. To observe the effects of vitamin E supplementation on these changes in order to evaluate the role of this anti-oxidant vitamin in reducing chronic haemolysis in G6PD deficient patients. A total number of 102 subjects with age ranged of 5 to 40 years of both sexes were included in the study. Among them 68 were G6PD enzyme deficient patients, of whom 34 were in supplemented group (experimental group) and 34 were in non-supplemented group (control group). The supplemented group received vitamin E supplementation for 60 consecutive days at a dose of 800 IU/day for adult and 400 IU/day for children ?12 years (in a divided dose, i.e., 4 times daily). Age and sex matched 34 apparently healthy subjects with normal blood G6PD level were taken to observe the base line data (healthy control) and also for comparison. All the G6PD deficient patients were selected from Out Patient Department (OPD) of Haematology, Banglabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2005 to June 2006 and all healthy subjects were selected from personal contact. Blood G6PD level, osmotic fragility of RBC were measured by standard techniques and MCV, MCH, and MCHC were obtained by calculation. All the parameters were measured on day 1 of their first visit and also were on day 60 in deficient group. Data were compared among the deficient groups, also in supplemented group just before and after supplementation. Analysis of data was done by appropriate statistical method. Mean starting and completing points of osmotic fragility of RBC were significantly higher but MCV. MCH, MCHC were significantly lower in patients suffering from

  4. Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events.

    Science.gov (United States)

    Martini, Dylan J; Hamieh, Lana; McKay, Rana R; Harshman, Lauren C; Brandao, Raphael; Norton, Craig K; Steinharter, John A; Krajewski, Katherine M; Gao, Xin; Schutz, Fabio A; McGregor, Bradley; Bossé, Dominick; Lalani, Aly-Khan A; De Velasco, Guillermo; Michaelson, M Dror; McDermott, David F; Choueiri, Toni K

    2018-04-01

    The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti-PD-1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7-46.5) and median TTP was 18.4 months (95% CI, 4.7-54.3) per Kaplan-Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients ( n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% ( n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti-PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti-PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402-8. ©2018 AACR . ©2018 American Association for Cancer Research.

  5. Functional connectivity in the basal ganglia network differentiates PD patients from controls

    Science.gov (United States)

    Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.L.; Rolinski, Michal; Duff, Eugene; Salimi-Khorshidi, Gholamreza; Filippini, Nicola; Zamboni, Giovanna; Hu, Michele T.M.

    2014-01-01

    Objective: To examine functional connectivity within the basal ganglia network (BGN) in a group of cognitively normal patients with early Parkinson disease (PD) on and off medication compared to age- and sex-matched healthy controls (HC), and to validate the findings in a separate cohort of participants with PD. Methods: Participants were scanned with resting-state fMRI (RS-fMRI) at 3T field strength. Resting-state networks were isolated using independent component analysis. A BGN template was derived from 80 elderly HC participants. BGN maps were compared between 19 patients with PD on and off medication in the discovery group and 19 age- and sex-matched controls to identify a threshold for optimal group separation. The threshold was applied to 13 patients with PD (including 5 drug-naive) in the validation group to establish reproducibility of findings. Results: Participants with PD showed reduced functional connectivity with the BGN in a wide range of areas. Administration of medication significantly improved connectivity. Average BGN connectivity differentiated participants with PD from controls with 100% sensitivity and 89.5% specificity. The connectivity threshold was tested on the validation cohort and achieved 85% accuracy. Conclusions: We demonstrate that resting functional connectivity, measured with MRI using an observer-independent method, is reproducibly reduced in the BGN in cognitively intact patients with PD, and increases upon administration of dopaminergic medication. Our results hold promise for RS-fMRI connectivity as a biomarker in early PD. Classification of evidence: This study provides Class III evidence that average connectivity in the BGN as measured by RS-fMRI distinguishes patients with PD from age- and sex-matched controls. PMID:24920856

  6. Corticomuscular coherence during hand gripping with DBS and medication in PD patients

    DEFF Research Database (Denmark)

    Sridharan, Kousik Sarathy; Højlund, Andreas; Johnsen, Erik Lisbjerg

    Deep brain stimulation (DBS) effectively alleviates the motor symptoms in Parkinson’s disease (PD) although its effect mechanism is still unclear. CMC is reduced in PD patients but restorable with medication, while DBS variably affects CMC in advanced PD patients. We recorded magnetoencephalography...... (MEG) from six PD patients performing hand gripping during DBS ON and medicated (levodopa, MED ON) conditions and from ten age-matched healthy controls. Participants performed isotonic contractions (hand gripping) with their right hand, and electromyography (EMG) was recorded from the extensor...... digitorum communis muscle with a belly-tendon montage. We calculated the mean-squared coherence between MEG and the rectified EMG signals. For each group and condition, we selected the maximum CMC value in the beta range (13-30 Hz) within the average of an a priori selection of nine left sensorimotor...

  7. Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among malaria patients in Upper Myanmar.

    Science.gov (United States)

    Lee, Jinyoung; Kim, Tae Im; Kang, Jung-Mi; Jun, Hojong; Lê, Hương Giang; Thái, Thị Lam; Sohn, Woon-Mok; Myint, Moe Kyaw; Lin, Khin; Kim, Tong-Soo; Na, Byoung-Kuk

    2018-03-16

    Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is one of the most common X-linked recessive hereditary disorders in the world. Primaquine (PQ) has been used for radical cure of P. vivax to prevent relapse. Recently, it is also used to reduce P. falciparum gametocyte carriage to block transmission. However, PQ metabolites oxidize hemoglobin and generate excessive reactive oxygen species which can trigger acute hemolytic anemia in malaria patients with inherited G6PD deficiency. A total of 252 blood samples collected from malaria patients in Myanmar were used in this study. G6PD variant was analysed by a multiplex allele specific PCR kit, DiaPlexC™ G6PD Genotyping Kit [Asian type]. The accuracy of the multiplex allele specific PCR was confirmed by sequencing analysis. Prevalence and distribution of G6PD variants in 252 malaria patients in Myanmar were analysed. Six different types of G6PD allelic variants were identified in 50 (7 females and 43 males) malaria patients. The predominant variant was Mahidol (68%, 34/50), of which 91.2% (31/34) and 8.8% (3/34) were males and females, respectively. Other G6PD variants including Kaiping (18%, 9/50), Viangchan (6%, 3/50), Mediterranean (4%, 2/50), Union (2%, 1/50) and Canton (2%, 1/50) were also observed. Results of this study suggest that more concern for proper and safe use of PQ as a radical cure of malaria in Myanmar is needed by combining G6PD deficiency test before PQ prescription. Establishment of a follow-up system to monitor potential PQ toxicity in malaria patients who are given PQ is also required.

  8. Factors Associated with Unplanned Dialysis Starts in Patients followed by Nephrologists: A Retropective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Pierre Antoine Brown

    Full Text Available The number of patients starting dialysis is increasing world wide. Unplanned dialysis starts (patients urgently starting dialysis in hospital is associated with increased costs and high morbidity and mortality. Risk factors for starting dialysis urgently in hospital have not been well studied. The primary objective of this study was to identify risk factors for unplanned dialysis starts in patients followed in a multidisciplinary chronic kidney disease (CKD clinic. We performed a retrospective cohort study of 649 advanced CKD patients followed in a multidisciplinary CKD clinic at a tertiary care hospital from January 01, 2010 to April 30, 2013. Patients were classified as unplanned start (in hospital or elective start. Multivariable logistic regression was used to identify variables associated with unplanned dialysis initiation. 184 patients (28.4% initiated dialysis, of which 76 patients (41.3% initiated dialysis in an unplanned fashion and 108 (58.7% starting electively. Unplanned start patients were more likely to have diabetes (68.4% versus 51.9%; p = 0.04, CAD (42.1% versus 24.1%; p = 0.02, congestive heart failure (36.8% versus 17.6%; p = 0.01, and were less likely to receive modality education (64.5% vs 89.8%; p < 0.01 or be assessed by a surgeon for access creation (40.8% vesrus 78.7% p < 0.01. On multivariable analysis, higher body mass index (OR 1.07, 95% CI 1.02, 1.13, and a history of congestive heart failure (OR 2.41, 95% CI 1.09, 5.41 were independently associated with an unplanned start. Unplanned dialysis initiation is common among advanced CKD patients, even if they are followed in a multidisciplinary chronic kidney disease clinic. Timely education and access creation in patients at risk may lead to lower costs and less morbidity and mortality.

  9. Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Lucy M Collins

    2018-02-01

    Full Text Available Background: Recently, the development of Parkinson’s disease (PD has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA mutations. Methods: We investigated PD and Gaucher Disease (GD patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.

  10. Patients' perceptions and illness severity at start of antidepressant treatment in general practice

    NARCIS (Netherlands)

    Van Geffen, Erica C.G.; Heerdink, Eiebert R.; Hugtenburg, Jacqueline G.; Siero, Frans W.; Egberts, Antoine C.G.; Van Hulten, Rolf

    2010-01-01

    Objectives Patients' perceptions are important to consider when trying to understand why patients often do not follow prescriptions for antidepressant treatment. This study aimed to investigate the influence of patients' perceptions and illness severity at the start on antidepressant-medication-

  11. PD-L1 Expression and Survival among Patients with Advanced Non-Small Cell Lung Cancer Treated with Chemotherapy

    DEFF Research Database (Denmark)

    Sørensen, Steffen Filskov; Zhou, Wei; Dolled-Filhart, Marisa

    2016-01-01

    with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD......-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9...... by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy....

  12. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

    Science.gov (United States)

    Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

    2013-01-01

    BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

  13. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections

    NARCIS (Netherlands)

    Tangden, T.; Martin, V.; Felton, T.W.; Nielsen, E.I.; Marchand, S.; Bruggemann, R.J.M.; Bulitta, J.B.; Bassetti, M.; Theuretzbacher, U.; Tsuji, B.T.; Wareham, D.W.; Friberg, L.E.; Waele, J.J. De; Tam, V.H.; Roberts, J.A.

    2017-01-01

    Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed.

  14. Timing of start of dialysis in diabetes mellitus patients: a systematic literature review.

    Science.gov (United States)

    Nacak, Hakan; Bolignano, Davide; Van Diepen, Merel; Dekker, Friedo; Van Biesen, Wim

    2016-02-01

    Diabetes mellitus is a frequent cause of the need for renal replacement therapy (RRT). Historically, RRT was started earlier in patients with diabetes, in an attempt to prevent complications of uraemia and diabetes. We did a systematic review to find support for this earlier start of dialysis in patients with versus without diabetes. The MEDLINE, EMBASE and CENTRAL databases were searched for articles about the timing of dialysis initiation in (subgroups of) patients with diabetes and CKD Stage 5. A total of 340 papers were screened and 11 papers were selected to be reviewed. Only three studies showed data of at least one subgroup of patients with diabetes. Two observational studies concluded that start of dialysis with a higher estimated glomerular filtration rate (eGFR) is beneficial with regard to survival, one did not find a difference and six observational studies concluded that start of dialysis with a lower eGFR is associated with better survival in patients with diabetes. The effect of timing of initiation of dialysis did not differ between patients with versus without diabetes. Lastly, one randomized controlled trial (two papers) reported that there was no difference in survival between start at higher versus lower eGFR overall and a P-value for the interaction with diabetes of P = 0.63, indicating no difference between patients with versus without diabetes with regard to the timing of start of dialysis and subsequent mortality on dialysis. There is no difference between early (eGFR) and late (lower eGFR) start of RRT with regard to mortality in patients with versus without diabetes. RRT should thus be initiated based on the same criteria in all patients, irrespective of the presence or absence of diabetes. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  15. Prognosis of bedridden patients with end-stage renal failure after starting hemodialysis.

    Science.gov (United States)

    Sugaya, Kimio; Hokama, Asanori; Hayashi, Eiri; Naka, Hidekatsu; Oda, Masami; Nishijima, Saori; Miyazato, Minoru; Hokama, Sanehiro; Ogawa, Yoshihide

    2007-06-01

    The mean age of starting hemodialysis (HD) in patients with end-stage renal failure is gradually increasing in Japan. It is not uncommon for HD to be commenced in bedridden elderly patients who cannot give informed consent, because of brain damage. However, we have not been able to provide useful advice to their families because there was no relevant information available about the prognosis of bedridden patients on HD. Therefore, we examined the prognosis of bedridden HD patients. Two hundred and nineteen patients who received HD were enrolled. These subjects were divided into five groups; (aged or=80 years at the commencement of HD), and we compared the overall prognosis between bedridden and nonbedridden patients, as well as that for each age group. There were 76 bedridden patients among the 219 HD patients, and the main cause of their bedridden state before starting HD was cerebrovascular disease. The 50% survival time after the start of HD was 120 months for the nonbedridden patients versus 56 months for bedridden patients. However, the mean (+/-SD) age of the bedridden patients was higher than that of nonbedridden patients (70 +/- 13 versus 64 +/- 14 years). In patients under age 50 years at the start of dialysis, the survival rate was lower in the bedridden than in the nonbedridden patients, but there were no differences between survival rates for bedridden and nonbedridden patients in the other four age groups. The prognosis of HD patients is poor compared with the general life expectancy of the Japanese population, but whether these patients are bedridden or not has little influence on their survival.

  16. [Increased expressions of peripheral PD-1+ lymphocytes and CD4+CD25+FOXP3+ T cells in gastric adenocarcinoma patients].

    Science.gov (United States)

    Li, Hao; Li, Songyan; Hu, Shidong; Zou, Guijun; Hu, Zilong; Wei, Huahua; Wang, Yufeng; Du, Xiaohui

    2017-01-01

    Objective To detect the frequencies of peripheral programmed death-1 + (PD-1 + ) lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in patients with gastric adenocarcinoma. Methods The study enrolled 29 patients with gastric adenocarcinoma and 29 age- and sex-matched healthy controls. Frequencies of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells were detected using flow cytometry. Results The number of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood was higher in patients with gastric adenocarcinoma than that in the control group. Moreover, linear correlation analysis indicated a positive correlation between PD-1 expression and frequency of CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood of the patients. Conclusion Gastric adenocarcinoma patients present with increased PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in the peripheral blood.

  17. Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Mónica Rodríguez

    2012-01-01

    Full Text Available We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes.

  18. PD_Manager: an mHealth platform for Parkinson's disease patient management.

    Science.gov (United States)

    Tsiouris, Kostas M; Gatsios, Dimitrios; Rigas, George; Miljkovic, Dragana; Koroušić Seljak, Barbara; Bohanec, Marko; Arredondo, Maria T; Antonini, Angelo; Konitsiotis, Spyros; Koutsouris, Dimitrios D; Fotiadis, Dimitrios I

    2017-06-01

    PD_Manager is a mobile health platform designed to cover most of the aspects regarding the management of Parkinson's disease (PD) in a holistic approach. Patients are unobtrusively monitored using commercial wrist and insole sensors paired with a smartphone, to automatically estimate the severity of most of the PD motor symptoms. Besides motor symptoms monitoring, the patient's mobile application also provides various non-motor self-evaluation tests for assessing cognition, mood and nutrition to motivate them in becoming more active in managing their disease. All data from the mobile application and the sensors is transferred to a cloud infrastructure to allow easy access for clinicians and further processing. Clinicians can access this information using a separate mobile application that is specifically designed for their respective needs to provide faster and more accurate assessment of PD symptoms that facilitate patient evaluation. Machine learning techniques are used to estimate symptoms and disease progression trends to further enhance the provided information. The platform is also complemented with a decision support system (DSS) that notifies clinicians for the detection of new symptoms or the worsening of existing ones. As patient's symptoms are progressing, the DSS can also provide specific suggestions regarding appropriate medication changes.

  19. Circulating Tumour DNA for Monitoring Treatment Response to Anti-PD-1 Immunotherapy in Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Atsuko Ashida

    2017-08-01

    Full Text Available Anti-programmed cell death-1 (anti-PD-1 antibody shows high therapeutic efficacy in patients with advanced melanoma. However, assessment of its therapeutic activity can be challenging because of tumour enlargement associated with intratumoural inflammation. Because circulating tumour DNA (ctDNA correlates with tumour burden, we assessed the value of ctDNA levels as an indicator of tumour changes. Quantification of ctDNA (BRAFmutant or NRASmutant levels by droplet digital PCR in 5 patients with BRAF or NRAS mutant melanoma during the treatment course showed dynamic changes corresponding to radiological and clinical alterations. In 3 cases in which the anti-PD-1 antibody was effective, ctDNA levels decreased within 2–4 weeks after treatment initiation. In 2 cases in which the anti-PD-1 antibody was ineffective, ctDNA levels did not decrease after treatment initiation. ctDNA could be a useful biomarker to predict early response to treatment in patients with advanced melanoma treated with anti-PD-1 immunotherapy.

  20. Urgent-Start Peritoneal Dialysis Complications: Prevalence and Risk Factors.

    Science.gov (United States)

    Xu, Damin; Liu, Tianjiao; Dong, Jie

    2017-07-01

    Mechanical complications are of particular concern in urgent-start peritoneal dialysis (PD) because of the shorter break-in period. However, risk factors have been reported inconsistently and data in urgent-start PD populations are limited. Observational cohort study. All patients treated with urgent-start PD, defined as PD therapy initiated within 1 week after catheter insertion, January 2003 to May 2013. Age, sex, abdominal surgery history, body mass index, hemoglobin level, albumin level, C-reactive protein level, break-in period (period between catheter insertion and PD therapy initiation), dialysate exchange volume, and use of overnight dwell. The presence of mechanical complications related to abdominal wall or catheter, including hernia, hydrothorax, hydrocele, subcutaneous leak, pericatheter leak, catheter malposition, omental wrap, and obstruction. 922 patients on urgent-start PD therapy were enrolled (mean age, 59.1±15.0 [SD] years). Prevalences of abdominal wall and catheter complications were 4.8% and 9.5%, respectively. The most common abdominal wall complication was hernia (55%), followed by hydrothorax (25%). On adjustment, male sex (HR, 5.41; 95% CI, 2.15-13.59; Pstart PD and conventional PD. Urgent-start PD is a safe and practicable approach. Male sex and history of abdominal surgery could contribute to the development of abdominal wall complications. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  1. PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2015-01-01

    Full Text Available On the basis of remarkable antitumor activity, programmed death receptor-1 (PD-1 inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma in the second-line setting following progression on either CTLA-4 inhibitor ipilimumab or BRAF/MEK inhibitors (for BRAF mutated melanoma. Given hypothesized risk of triggering exacerbations of autoimmune diseases and/or chronic viral infections, clinical trials (including regulatory studies evaluating checkpoint blocking antibodies PD-1 and CTLA-4 have excluded patients with autoimmune diseases, chronic hepatitis B/C virus (HBV/HCV, and/or human immunodeficiency virus (HIV infections. Herein, we describe two patients with advanced melanoma and concomitant HCV/HIV infections treated with PD-1 inhibitor pembrolizumab. Patient 2 with HIV/HCV coinfection progressed after 2 doses of pembrolizumab. Patient 1 who had HCV alone was treated with pembrolizumab with initial partial response. HCV viral load remained stable after 9 cycles of pembrolizumab following which 12-week course of HCV-directed therapy was commenced, resulting in prompt reduction of HCV viral load below detectable levels. Response is ongoing and HCV viral load remains undetectable. In both patients, no significant toxicities were observed when pembrolizumab was initiated. We argue for the further investigation of checkpoint inhibition in cancer patients with underlying chronic viral infections in the context of carefully designed clinical trials.

  2. Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy

    Science.gov (United States)

    Balermpas, Panagiotis; Martin, Daniel; Wieland, Ulrike; Rave-Fränk, Margret; Strebhardt, Klaus; Rödel, Claus; Fokas, Emmanouil; Rödel, Franz

    2017-01-01

    ABSTRACT We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8+ tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16INK4a expression. After a median follow-up of 40 mo (1–205 mo), the 5-y cumulative incidence of local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker expression was significantly more common in tumors with high HPV16 viral load. In multivariant analysis, high CD8+ and PD-1+ TILs expression predicted for improved local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p = 0.014, respectively). Also, high p16INK4a (p = 0.011) and PD-L1 (p = 0.033) expression predicted for better local control, whereas high FOXP3+ Tregs (p = 0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with superior DFS. Female sex and high HPV16 viral load correlated with favorable outcome for all three clinical endpoints. The present data provide, for the first time, robust explanation for the favorable clinical outcome of HPV16-positive ASCC patients harboring strong immune cell infiltration. Our findings are relevant for treatment stratification with immune PD-1/PD-L1 checkpoint inhibitors to complement CRT and should be explored in a clinical trial. PMID:28405521

  3. Does peritoneal dialysis have a role in urgent-start end-stage kidney disease?

    Science.gov (United States)

    McQuillan, Rory F; Lok, Charmaine E

    2018-04-19

    Despite its many positive attributes, peritoneal dialysis remains underutilized, particularly in the United States. Urgent-start peritoneal dialysis (PD) has been proposed as a method of increasing PD prevalence. Urgent-start PD has been shown to be safe, feasible, and effective. However, urgent-start PD is also accompanied by several multidimensional challenges. This article is intended to equip the reader with a practical sense of whether an urgent-start PD program would be appropriate in his or her own clinical context and if appropriate, what factors would be necessary for such a program to flourish. As such, we summarize latent factors, which are necessary to consider before instituting an urgent-start PD. Then, using a series of clinical vignettes, highlight the component parts of a successful urgent-start PD program and the patient population who stand to benefit most from this strategy. The discussion is then balanced by presenting limitations to consider in the urgent-start PD approach. © 2018 Wiley Periodicals, Inc.

  4. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013

    DEFF Research Database (Denmark)

    Trickey, Adam; May, Margaret T.; Vehreschild, Jorg Janne

    2017-01-01

    Background Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year...... survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013. Methods We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between...... ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART. Findings 88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second...

  5. Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment

    DEFF Research Database (Denmark)

    May, Margaret T; Vehreschild, Jorg-Janne; Trickey, Adam

    2016-01-01

    BACKGROUND: CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. METHODS: We estimated mortality rates (MRs) by time since start of ART (...-4.9, 5-9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996-2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996-1997, 1998-1999, 2000......-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/µL) overall and separately according to time since start of ART. RESULTS: A total of 6344 of 37 496 patients died during 359 219...

  6. Seroprevalence of Anti-HCV Antibody in Patients with Chronic Kidney Disease before Starting Dialysis Therapy

    Directory of Open Access Journals (Sweden)

    Fareha Jesmin Rabbi

    2017-01-01

    Full Text Available Background: Hepatitis C virus (HCV infection and chronic kidney disease are common and potentially serious medical problems throughout the world. In recent years, it has become clear that these two conditions are linked in several important ways. Indeed, some forms of renal diseases are precipitated by HCV infection and patients with end-stage renal disease (ESRD are at increased risk for acquiring HCV infection. Patients with chronic kidney disease typically show an impaired immune response compared with healthy individuals and also other risk factors related with treatment and management. CKD patients ultimately undergo end stage renal therapy like dialysis for their treatment and survival. Risk factors for the infections are more in dialysis period than in predialytic stages. Like other developing countries CKD patients with HCV infection are very common in our country. For this reason the CKD patients should be properly diagnosed knowing the infection status before dialysis which would help both the patient and doctor to choose their proper treatment approach. Objective: This cross-sectional study was done to know the prevalence of HCV infection in the CKD patients before starting dialysis therapy. Materials and Methods: A total of 197 patients with chronic kidney disease stage five (CKD-V before starting dialysis therapy were included as subjects of this study. Among the CKD patients anti-HCV was detected to see prevalence of hepatitis C virus infection. The patients were also tested for HBsAg to assess co-infection. After collecting all the data of different test results analyses were done by SPSS version 15.0. Results: In this study 195 (99% patients were anti-HCV negative and only two patients (1% were found positive. Conclusion: HCV infection in CKD patients before dialysis should be taken into account so that HCV negative CKD patients would not get the infection during dialysis and standard screening procedures should be taken to

  7. Systematic review of patient handling activities starting in lying, sitting and standing positions.

    Science.gov (United States)

    Hignett, Sue

    2003-03-01

    Over the last 20 years a number of methods have been recommended in professional guidelines for moving patients. This review was undertaken as it was recognized that there was a need for clinical work involving handling patients (systems of work and equipment) to be based on scientific evidence. The aim of this paper is to report the methodology, search strategy and results relating to work involving the care, treatment and transfer of patients starting in lying, sitting and standing positions. An unusual philosophical stance has been taken by appraising studies within a study type rather than comparatively. This facilitated the inclusion of a wide range of study designs (quantitative and qualitative). A string search was run on eight databases and supplemented by other search strategies. A published checklist was selected and inter-rater reliability established before the main review commenced. A systematic process for inclusion, exclusion, appraisal, extraction and synthesis was undertaken. Thirty-two studies were included: nine for activities with the patient starting in a lying position and 23 for the sitting position. No studies were found with respect to patient handling activities starting in a standing position. These data were synthesized into evidence statements. The evidence statements support the use of hoists (for nonweight bearing patients), standaids, sliding sheets (double thickness rollers), lateral transfer boards, walking belts and adjustable height beds and baths. It is suggested that these items should constitute a minimum equipment list for any clinical environment where patient handling takes place on a regular basis. The lack of research relating to patient handling in standing is of particular concern and it is recommended that this area should be a high research priority to address concerns about patient handling in rehabilitation activities.

  8. [DIETARY INTAKE AND NUTRITIONAL STATUS IN ONCOLOGY PATIENTS WHO START TREATMENT WITH TYROSINE KINASE INHIBITORS].

    Science.gov (United States)

    Higuera-Pulgar, Isabel; Ribed, Almudena; Carrascal-Fabian, M Luisa; Bretón-Lesmes, Irene; Romero-Jiménez, Rosa M; Cuerda-Compes, Cristina; Velasco-Gimeno, Cristina; Camblor-Álvarez, Miguel; García-Peris, Pilar

    2015-09-01

    in recent years, researching about new oral antineoplastics has progressed while its impact on dietary intake and nutritional status (NS) hasn't developed enough yet. dietary intake and NS assessment in patients who start treatment with tyrosine kinase inhibitors (TKI) and evaluate its impact on them. an observational, prospective-six-months study, in which were included patients starting treatment with TKI. The intake was evaluated by a 24 h dietary record and a food frequency questionnaire. The NS was evaluated by anthropometric measurements and the patient-generated Global Subjective Assessment (PG-GSA); the results were compared with the Spanish references (SENC-semFYC, 2007 and O. Moreiras, 2013). Friedman test, χ2, Wilcoxon, Kruskal-Wallis and Mann-Whitney were used in the statistical analysis. Significance p Weight loss was no significant, although a high percentage of the energy and protein requirements hadn't been reached. The caloric intake was positively related with the number of meals. Dietary habits did not change during treatment. dietary intake did not reach nutritional requirements at baseline. The TKI don't seem to affect the patient's intake and nutritional status. The research about these parameters before starting treatment could prevent future complications and it would guide the dietary advice. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  9. EVALUATION OF NUTRITIONAL STATUS IN PERITONEAL DIALYSIS (PD PATIENTS

    Directory of Open Access Journals (Sweden)

    Max Dratwa

    2012-06-01

    anthropometric,BMI and biochemical measurements, SGA, Brandes score, total (renal and peritoneal creatinine excretion, dietician records, handgrip strength, DEXA, multifrequency electrical bioimpedance (TBIA. Daily dietary protein intake was less than 1g/kg ideal BW in 35 % of pts while 38% ate more than 1.2 g/kg; daily total (oral and peritoneal caloric intake was 28±8 kcal/kg. Fifteen % of patients (median age 71 had a very low serum albumin level ( 50 g/l (median age 64 years. Very significant correlations were found between: 1 estimation of fat mass by skinfold thickness and that modelised from the water volume determined by TBIA (r²: 0.56, p<0.0001; 2 brachial circumference and lean body mass determined by TBIA (but no correlation between middle arm circumference and handgrip strength ; 3 muscle mass determined by creatinine kinetics and TBIA (r²: 0.68, p<0.001; 4 muscle mass estimated by brachial circumference and lean body mass estimated through creatinine kinetics; 5 handgrip strength and lean body mass determined both by TBIA and by creatinine kinetics (r²: 0.59, p<0.0001; 6 lean body mass and age (but different between males and females; 7 protein losses in the dialysate and lean body mass derived from creatinine kinetics. In conclusion, malnutrition is more threatening as patients age. Patients with a low initial lean body mass and low protein intakes should be closely monitored such as protein losses do not counterbalance the theoretical advantages of a higher dialysis dose.

  10. When antithyroid drugs must be started in patients with hyperemesis gravidarum

    International Nuclear Information System (INIS)

    Farzad, N.; Akbar, A.; Naser, A.; Majid, M.

    2009-01-01

    To find out role of anti-thyroid drugs in patients with Hyperemesis gravidarum and thyroid dysfunction. One hundred thirty five patients with hyperemesis gravidarum who were admitted to obstetric and gynecology hospital were enrolled in this study. Thirty two patients were excluded because of diabetes mellitus and thyroid diseases. Hence, one hundred three patients underwent investigations including thyroid function test and beta-hCG (Human chorionic gonadotropin). Thirty five women were found with abnormal thyroid function test with FT4I (Free Thyroxin Index) 4.74 +- 0.54 and in another group (68 women) was 2.9 +- 0.39 (P<0.0001). B-hCG in first group was 59406 +-14899 miu/ml and in second group was 6750 +- m 3476 miu/mL (P<0.0001). In five patients PTU (propylthiouracil) was started due to severe sign and symptoms of hyperthyroidism. Thyroid function test was rechecked for all of 35 patients after four weeks routine therapy for hyperemesis gravidarum. Thyroid function test was normalized in 11 patients with hyperemesis graridarum but remained abnormal in 22 patients. In our study thyroid dysfunction in hyperemesis gravidarum was 35% and, 20% of patients needed anti-thyroid therapy. Routine assessment of thyroid function is necessary for women with hyperemesis gravidarum especially in patients with clinical features of hyperthyroidism. We must consider PTU (propylthouracil) in hyperemesis gravidarum with severe weight loss, vomiting and biochemical hyperthyroidism. (author)

  11. Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: a meta-analysis.

    Science.gov (United States)

    Dai, Cong; Wang, Meng; Lu, Jun; Dai, Zhiming; Lin, Shuai; Yang, Pengtao; Tian, Tian; Liu, Xinghan; Min, Weili; Dai, Zhijun

    2017-01-01

    PD-L1 has been reported to be expressed in diverse human malignancies. However, the prognostic value of PD-L1 in digestive system cancers remains inconclusive. Therefore, we conducted this meta-analysis to evaluate the prognostic impact of PD-L1 expression in digestive system cancers. We searched the PubMed, Embase, and the Chinese National Knowledge Infrastructure for publications concerning PD-L1 expression in digestive system cancers. Correlations of PD-L1 expression level with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were analyzed. Finally, 32 studies with 7,308 patients were included. Our results show that PD-L1 expression was significantly associated with poorer OS (hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.18-1.76, P digestive system cancers, especially in gastric cancer and pancreatic cancer. In addition, PD-L1 may act as a new parameter for predicting poor prognosis and a promising target for anticancer therapy in digestive system cancers.

  12. Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Ruiz, Lidia; Cozzi-Lepri, Alessandro

    2008-01-01

    OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) wi...

  13. Imipenem in burn patients: pharmacokinetic profile and PK/PD target attainment.

    Science.gov (United States)

    Gomez, David S; Sanches-Giraud, Cristina; Silva, Carlindo V; Oliveira, Amanda M Ribas Rosa; da Silva, Joao Manoel; Gemperli, Rolf; Santos, Silvia R C J

    2015-03-01

    Unpredictable pharmacokinetics (PK) in burn patients may result in plasma concentrations below concentrations that are effective against common pathogens. The present study evaluated the imipenem PK profile and pharmacokinetic/pharmacodynamics (PK/PD) correlation in burn patients. Fifty-one burn patients, 38.7 years of age (mean), 68.0 kg, 36.3% total burn surface area (TBSA), of whom 84% (43/51) exhibited thermal injury, 63% inhalation injury and 16% electrical injury (8/51), all of whom were receiving imipenem treatment were investigated. Drug plasma monitoring, PK study (120 sets of plasma levels) and PK/PD correlation were performed in a series of blood samples. Only 250 μl of plasma samples were required for drug plasma measurements using the ultra filtration technique for the purification of biological matrix and quantification using liquid chromatography. Probability of target attainment (PTA) was calculated using a PD target of 40% free drug concentrations above the minimum inhibitory concentration (40%fT>MIC). Significant differences in PK parameters (medians), such as biological half-life (2.2 vs 5.5 h), plasma clearance (16.2 vs 1.4 l h(-1)) and volume of distribution (0.86 vs 0.19 l kg(-1)), were registered in burn patients via comparisons of set periods with normal renal function against periods of renal failure. Correlations between creatinine clearance and total body plasma clearance were also obtained. In addition, the PK profile did not change according to TBSA during sets when renal function was preserved. PTA was >89% for MIC values up to 4 mg l(-1). In conclusion, imipenem efficacy for the control of hospital infection on the basis of PK/PD correlation was guaranteed for burn in patients at the recommended dose regimens for normal renal function (31.1±9.7 mg kg(-1) daily), but the daily dose must be reduced to 17.2±9.7 mg kg(-1) during renal failure to avoid neurotoxicity.

  14. [Satisfaction of patients with type 2 diabetes mellitus after starting treatment with insulin].

    Science.gov (United States)

    Mancera-Romero, J; Carramiñana-Barrera, F; Muñoz-González, L; Guillén-Álvarez, P; Murillo-García, D; Sánchez-Pérez, M R

    2016-01-01

    The objective of this study is to evaluate if overcoming the barrier of starting treatment with insulin can lead to better clinical control and a higher level of patient satisfaction with their treatment. This is an observational, multicentre study of patients diagnosed with DM2 who attended primary care centres with poor glycaemic control (A1c≥8%) under treatment with oral antidiabetic drugs (OADs), and who were given motivational treatment to overcome their fear of injections, and started treatment with insulin. The level of satisfaction with the treatment was evaluated using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). The questionnaire was used before initiating the treatment with insulin and in the follow-up visit (3-4 months from the beginning of treatment with basal insulin). A total of 573 patients with a mean age of 64±10 years were recruited. The overall mean score from the DTSQs satisfaction questionnaire was 18.3±6.3, and the change of treatment led to an improvement in patient satisfaction compared to the previous treatment (DTSQc mean score 8.8±5.9). A1c dropped from an initial value of 8.7% (SD 0.8) to 7.5% (SD 0.7) (P<.001). The frequency of hyperglycaemic episodes perceived by the patients was significantly lower after they overcame their fear of injections (35.6% compared to 11.5%; P<.001), but no statistically significant differences were found in the frequency of hypoglycaemic episodes (32% compared to 35%; P=.059). In patients with DM2 poorly controlled with OADs, overcoming a fear of injections and starting treatment with insulin was associated with an overall improvement in satisfaction with the new treatment, and decreased the perception of hyperglycaemic episodes. Glycaemic control and the metabolic profile of the patients also improved to a statistically significant degree with the change of treatment. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S

  15. Should patients with esophageal atresia be submitted to esophageal substitution before they start walking?

    Science.gov (United States)

    Tannuri, U; Tannuri, A C A

    2011-01-01

    Esophagocoloplasty and gastric transposition are two major methods for esophageal substitution in children with esophageal atresia, and there is broad agreement that these operations should not be performed before the children start walking. However, there are some reported advantages of performing such operations in the first months of life or in the neonatal period. In this study, we compared our experience with esophageal substitution procedures performed in walking children with esophageal atresia, with the outcomes of children who had the operation before the third month of life reported in the literature. The purpose of this study was to establish if we have to wait until the children start walking before indicating the esophageal replacement procedure. From February 1978 to October 2009, 129 children with esophageal atresia underwent esophageal replacement in our hospital (99 colonic interpositions and 30 gastric transpositions). The records of these patients were reviewed for data regarding demographics, complications (leaks, graft failures, strictures, and graft torsion), and mortality and compared with those reported in the two main articles on esophageal replacement in the neonatal period or in patients less than 3 months of age. The main complication of our casuistic was cervical anastomosis leakage, which sealed spontaneously in all except in four patients. One patient of the esophagocoloplasty group developed graft necrosis and three patients in the gastric transposition group had gastric outlet obstruction, secondary to axial torsion of the stomach placed in the retrosternal space. The long-term outcome of the patients in both groups was considered good to excellent in terms of normal weight gain, absence of dysphagia, and other gastrointestinal symptoms. The comparisons of the main complications and mortality rates in walking children with esophageal substitutions performed in the first months of life showed that the incidences of cervical

  16. Gender differences in patients starting long-term home mechanical ventilation due to obesity hypoventilation syndrome.

    Science.gov (United States)

    Palm, Andreas; Midgren, Bengt; Janson, Christer; Lindberg, Eva

    2016-01-01

    Obesity hypoventilation syndrome (OHS) is often diagnosed late. The aim of this study was to analyse gender differences at initiation of long-term mechanical ventilation (LTMV) in patients with (OHS), to analyse gender differences in treatment effect and to study how the prescription of LTMV due to OHS has changed over time. Data on patients on LTMV due to OHS between 1996 and 2014 were obtained from Swedevox, a nationwide health quality registry of patients on LTMV in Sweden. When starting LTMV, women were generally older (age 64.4 ± 11.2 vs. 60.1 ± 12.1 years, p obese (BMI 43.0 ± 8.2 vs. 41.5 ± 7.9 kg/m2, p differ. During the study period, the age of patients at the initiation of LTMV rose by 3.4 years/decade (P = 0.001) in women and with 1.9 years/decade (P = 0.048) in men but there were no significant changes in BMI (P = 0.425). Diagnosis of OHS is more delayed in women and as a consequence the disease is more advanced when diagnosed. In spite of this, there is no gender difference in survival rate in patients with OHS treated with LTMV. More and older patients with OHS nowadays gain access to LTMV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Mortality in primary angioplasty patients starting antiplatelet therapy with prehospital prasugrel or clopidogrel

    DEFF Research Database (Denmark)

    Goldstein, Patrick; Grieco, Niccolò; Ince, Hüseyin

    2016-01-01

    hospitalization, we report here the 1-year follow-up data, including cardiovascular (CV) mortality. METHODS AND RESULTS: MULTIPRAC is a multinational, prospective registry of patients with ST-elevation myocardial infarction (STEMI) from 25 hospitals in nine countries, all of which had an established practice...... of prehospital start of dual antiplatelet therapy in place. The key outcome was CV death at 1 year. Among 2,036 patients followed-up through 1 year, 49 died (2.4%), 10 during the initial hospitalization and 39 within 1 year after hospital discharge. The primary analysis was based on the P2Y12-inhibitor, used...... from prehospital loading dose through hospital discharge. Prasugrel (n=824) was more commonly used than clopidogrel (n=425). The observed 1-year rates for CV death were 0.5% with prasugrel and 2.6% with clopidogrel. After adjustment for differences in baseline characteristics, treatment with prasugrel...

  18. Youth, unemployment, and male gender predict mortality in AIDS patients started on HAART in Nigeria.

    Science.gov (United States)

    DeSilva, Malini B; Merry, Stephen P; Fischer, Philip R; Rohrer, James E; Isichei, Christian O; Cha, Stephen S

    2009-01-01

    This retrospective study identifies risk factors for mortality in a cohort of HIV-positive adult patients treated with highly active antiretroviral therapy (HAART) in Jos, Nigeria. We analyzed clinical data from a cohort of 1552 patients enrolled in a HIV/acquired immune deficiency syndrome treatment program and started on HAART between December 2004 and 30 April 2006. Death was our study endpoint. Patients were followed in the study until death, being lost to follow-up, or the end of data collection, 1 December 2006. Baseline patient characteristics were compared using Wilcoxon Rank Sum Test for continuous variables and Pearson Chi-Square test for categorical variables to determine if certain demographic factors were associated with more rapid progression to death. The Cox proportional hazard multivariate model analysis was used to find risk factors. As of 1 December 2006, a total of 104 cases progressed to death. In addition to the expected association of CD4 count less than 50 at initiation of therapy and active tuberculosis with mortality, the patient characteristics independently associated with a more rapid progression to death after initiation of HAART were male gender, age less than 30 years old, and unemployment or unknown occupation status. Future research is needed to identify the confounding variables that may be amenable to targeted interventions aimed at ameliorating these health disparities.

  19. Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer.

    Science.gov (United States)

    Cho, Jong Ho; Zhou, Wei; Choi, Yoon-La; Sun, Jong-Mu; Choi, Hyejoo; Kim, Tae-Eun; Dolled-Filhart, Marisa; Emancipator, Kenneth; Rutkowski, Mary Anne; Kim, Jhingook

    2018-01-01

    Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor ( EGFR )-mutant non-small cell lung cancer (NSCLC). We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR -mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis. All patients had ≥1 EGFR mutation-54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1-positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1-positive groups (TPS ≥ 1%) compared with the PD-L1-negative group (median, 35 months). PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR -mutant NSCLC.

  20. Impaired Tumor-infiltrating T Cells in Patients with COPD Impacts Lung Cancer Response to PD-1 Blockade.

    Science.gov (United States)

    Biton, Jérôme; Ouakrim, Hanane; Dechartres, Agnès; Alifano, Marco; Mansuet-Lupo, Audrey; Si, Han; Halpin, Rebecca; Creasy, Todd; Bantsimba-Malanda, Claudie; Arrondeau, Jennifer; Goldwasser, François; Boudou-Rouquette, Pascaline; Fournel, Ludovic; Roche, Nicolas; Burgel, Pierre-Régis; Goc, Jeremy; Devi-Marulkar, Priyanka; Germain, Claire; Dieu-Nosjean, Marie-Caroline; Cremer, Isabelle; Herbst, Ronald; Damotte, Diane

    2018-03-08

    Patients with chronic obstructive pulmonary disease (COPD) have a higher prevalence of lung cancer. The chronic inflammation associated with COPD probably promotes the earliest stages of carcinogenesis. However, once tumors have progressed to malignancy, the impact of COPD on the tumor immune microenvironment remains poorly defined, and its effects on immune-checkpoint blockers' efficacy are still unknown. To study the impact of COPD on the immune contexture of non-small cell lung cancer (NSCLC). We performed in depth immune profiling of lung tumors by immunohistochemistry and we determined its impact on patients' survival (n=435). Tumor-infiltrating T lymphocyte (TILs) exhaustion by flow cytometry (n=50) was also investigated. The effectiveness of an anti-PD-1 treatment (nivolumab) was evaluated in 39 advanced-stage NSCLC patients. All data were analyzed according to patients' COPD status. Measurments and Main Results: Remarkably, COPD severity is positively correlated with the coexpression of PD-1/TIM-3 by CD8 T cells. In agreement, we observed a loss of CD8 T cell-associated favorable clinical outcome in COPD+ patients. Interestingly, a negative prognostic value of PD-L1 expression by tumor cells was observed only in highly CD8 T cell-infiltrated tumors of COPD+ patients. Finally, data obtained on 39 advanced-stage NSCLC patients treated by an anti-PD-1 antibody showed longer progression free survival in COPD+ patients, and also that the association between the severity of smoking and the response to nivolumab was preferentially observed in COPD+ patients. COPD is associated with an increased sensitivity of CD8 TILs to immune escape mechanisms developed by tumors, thus suggesting a higher sensitivity to PD-1 blockade in patients with COPD.

  1. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

    Science.gov (United States)

    Ho, Li-Chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-08-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.

  2. Immune recovery after starting ART in HIV-infected patients presenting and not presenting with tuberculosis in South Africa.

    Science.gov (United States)

    Schomaker, Michael; Egger, Matthias; Maskew, Mhairi; Garone, Daniela; Prozesky, Hans; Hoffmann, Christopher J; Boulle, Andrew; Fenner, Lukas

    2013-05-01

    We studied the immune response after starting antiretroviral treatment (ART) in 15,646 HIV-infected patients with or without tuberculosis (TB) at presentation in 3 ART programs in South Africa between 2003 and 2010. Patients presenting with TB had similar increases in CD4 cells compared with all other patients (adjusted difference 4.9 cells/µL per 6 months, 95% confidence interval: 0.2 to 9.7). Younger age, advanced clinical stage, female sex, and lower CD4 cell count at ART start were all associated with steeper CD4 slopes. In South Africa, HIV-infected patients presenting with TB experience immune recovery after starting ART that is no worse than in other patients.

  3. Dietary resilience in patients with severe COPD at the start of a pulmonary rehabilitation program

    Directory of Open Access Journals (Sweden)

    ter Beek L

    2018-04-01

    Full Text Available Lies ter Beek,1–3 Hester van der Vaart,2 Johan B Wempe,2 Aliaksandra O Dzialendzik,4 Jan LN Roodenburg,3 Cees P van der Schans,1,5,6 Heather H Keller,7,8 Harriët Jager-Wittenaar1,3 1Hanze University of Applied Sciences, Research Group Healthy Ageing, Allied Health Care and Nursing, Groningen, the Netherlands; 2University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Center for Rehabilitation, Groningen, the Netherlands; 3University of Groningen, University Medical Center Groningen, Department of Maxillofacial Surgery, Groningen, the Netherlands; 4Hanze University of Applied Sciences, Department of Applied Psychology, Groningen, the Netherlands; 5University of Groningen, University Medical Center Groningen, Department of Rehabilitation Medicine, Groningen, the Netherlands; 6University of Groningen, University Medical Center Groningen, Health Psychology Research, Groningen, the Netherlands; 7University of Waterloo, Schlegel Research Institute for Aging, Waterloo, ON, Canada; 8University of Waterloo, Department of Kinesiology, Waterloo, ON, Canada Background: COPD may impact food-related activities, such as grocery shopping, cooking, and eating. Decreased food intake may result in an unhealthy diet, and in malnutrition, which is highly prevalent in patients with COPD. Malnutrition is known to negatively impact clinical outcome and quality of life. Aims: In this qualitative study, we aimed to explore strategies used to overcome food-related challenges, ie, dietary resilience, and whether these led to a healthy diet. Furthermore, we aimed to identify the key themes of motivation for dietary resilience in patients with severe COPD. Methods: In October 2015 to April 2016, 12 patients with severe COPD starting a pulmonary rehabilitation program were interviewed. Qualitative description and thematic analysis were performed. Results: All participants mentioned the use of strategies to overcome

  4. From DTCA-PD to patient information to health information: the complex politics and semantics of EU health policy.

    Science.gov (United States)

    Brooks, Eleanor; Geyer, Robert

    2012-12-01

    Between 2001 and 2011 the pharmaceutical industry, supported by DG Enterprise, was engaged in an ongoing campaign to repeal/amend the European Union (EU) ban on direct-to-consumer advertising of prescription drugs (DTCA-PD). As it became increasingly clear that the ban would not be repealed, DTCA-PD supporters tried to shift the debate away from advertising and towards the provision of 'patient information' and the rights of patients to access such information. Meanwhile, a variety of national and European health organizations, supported by DG SANCO, sought to maintain the ban and oppose the industry-supported 'patient information' campaign. Instead, they promoted a concept of 'health information' that included all aspects of citizens' health, not just pharmaceuticals. This article aims to analyse the transition from DTCA-PD to patient information to health information and examine its implications for EU health policy as a complex policy space. The article examines the emergence and development of EU health policy and the evolution of the DTCA-PD debate through the lens of complexity theory. It analyses the nature of the semantic, political and policy transition and asks why it occurred, what it tells us about EU health policy and future EU health legislation and how it may be understood from a complexity perspective. The article concludes that the complexity framework is ideally suited for the field of public health and, in particular, the DTCA-PD debate. Having successfully shifted the policy-focus of the debate to patients' rights and health information, opponents of the legislation are likely to face their next battle in the realm of cyberspace, where regulatory issues change the nature of advertising. © 2012 Blackwell Publishing Ltd.

  5. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Trickey, Adam; May, Margaret T; Vehreschild, Jorg-Janne

    2016-01-01

    OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing to the Antiretro......OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing...... to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. RESULTS: During 50,593 person...... years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict...

  6. Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia.

    Science.gov (United States)

    Zhu, Liuluan; Kong, Yaxian; Zhang, Jianhong; Claxton, David F; Ehmann, W Christopher; Rybka, Witold B; Palmisiano, Neil D; Wang, Ming; Jia, Bei; Bayerl, Michael; Schell, Todd D; Hohl, Raymond J; Zeng, Hui; Zheng, Hong

    2017-06-19

    T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML. Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression was examined by flow cytometry. The correlation of Blimp-1 expression to clinical characteristics of AML patients was analyzed. Phenotypic and functional studies of Blimp-1-expressing T cells were performed using flow cytometry-based assays. Luciferase reporter assays and ChIP assays were applied to assess direct binding and transcription activity of Blimp-1. Using siRNA to silence Blimp-1, we further elucidated the regulatory role of Blimp-1 in the TIGIT and PD-1 expression and T cell immune response. Blimp-1 expression is elevated in T cells from AML patients. Consistent with exhaustion, Blimp-1 + T cells upregulate multiple inhibitory receptors including PD-1 and TIGIT. In addition, they are functionally impaired manifested by low cytokine production and decreased cytotoxicity capacity. Importantly, the functional defect is reversed by inhibition of Blimp-1 via siRNA knockdown. Furthermore, Blimp-1 binds to the promoters of PD-1 and TIGIT and positively regulates their expression. Our study demonstrates an important inhibitory effect of Blimp-1 on T cell response in AML; thus, targeting Blimp-1 and its regulated molecules to improve the immune response may provide effective leukemia therapeutics.

  7. Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Liuluan Zhu

    2017-06-01

    Full Text Available Abstract Background T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM domain (TIGIT and programmed cell death protein 1 (PD-1 are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML. In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1 in T cell response and transcriptional regulation of TIGIT and PD-1 in AML. Methods Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression was examined by flow cytometry. The correlation of Blimp-1 expression to clinical characteristics of AML patients was analyzed. Phenotypic and functional studies of Blimp-1-expressing T cells were performed using flow cytometry-based assays. Luciferase reporter assays and ChIP assays were applied to assess direct binding and transcription activity of Blimp-1. Using siRNA to silence Blimp-1, we further elucidated the regulatory role of Blimp-1 in the TIGIT and PD-1 expression and T cell immune response. Results Blimp-1 expression is elevated in T cells from AML patients. Consistent with exhaustion, Blimp-1+ T cells upregulate multiple inhibitory receptors including PD-1 and TIGIT. In addition, they are functionally impaired manifested by low cytokine production and decreased cytotoxicity capacity. Importantly, the functional defect is reversed by inhibition of Blimp-1 via siRNA knockdown. Furthermore, Blimp-1 binds to the promoters of PD-1 and TIGIT and positively regulates their expression. Conclusions Our study demonstrates an important inhibitory effect of Blimp-1 on T cell response in AML; thus, targeting Blimp-1 and its regulated molecules to improve the immune response may provide effective leukemia therapeutics.

  8. Sleep disturbances in drug naïve Parkinson′s disease (PD patients and effect of levodopa on sleep

    Directory of Open Access Journals (Sweden)

    Teresa Ferreira

    2014-01-01

    Full Text Available Context: Parkinson′s disease (PD is associated with sleep disturbances, attributed to the neurodegenerative process and therapeutic drugs. Studies have found levodopa to increase wakefulness in some patients while increasing sleepiness in others. Aims: To confirm sleep disturbances in drug naïve PD patients and understand the impact of levodopa on their sleep. Materials and Methods: Twenty-three drug naοve PD patients and 31 age-gender matched controls were compared using the Parkinson′s Disease Sleep Scale (PDSS and Epworth Sleepiness Scale (ESS. A polysomnogram objectively compared sleep quality. Of the 23 patients, the 12 initiated on levodopa were reassessed subjectively and through polysomnography after 2 months of therapy. Statistical Analysis: Data was expressed as mean ± standard deviation, median, and range. Continuous variables were analyzed by Student′s T test for normally distributed data and Mann-Whitney U test for skewed data. Discrete variables were compared by Chi Square tests (Pearson Chi square Test or Fisher′s Exact Test. Wilcoxon signed ranks test was applied in the analysis of paired data pre- and post-levodopa. A P value < 0.05 was considered as statistically significant. Statistical analysis of the data was done using the Statistical Package for the Social Sciences (SPSS version 12. Results: Drug naïve PD patients had lower PDSS scores than controls. The sleep architecture changes observed on polysomnogram were reduced NREM Stage III and REM sleep and increased sleep latency and wake after sleep onset time. Following levodopa, improved sleep efficiency with reduced sleep latency and wake after sleep onset time was noted, coupled with improved PDSS scores. However, NREM Stage III and REM sleep duration did not increase. Discussion: PD patients take longer to fall asleep and have difficulty in sleep maintenance. Sleep maintenance is affected by nocturia, REM behavioral disorder, nocturnal cramps, akinesia, and

  9. Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy

    DEFF Research Database (Denmark)

    Wallman, Johan K; Jöud, Anna; Olofsson, Tor

    2017-01-01

    Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before...

  10. Clinical characteristics with an impact on ADL functions of PD patients with cognitive impairment indicative of dementia.

    Directory of Open Access Journals (Sweden)

    Inga Liepelt-Scarfone

    Full Text Available BACKGROUND: Dementia in Parkinson's disease (PD is defined as cognitive decline severe enough to affect activities of daily living function (ADL. The aim of our exploratory study was to compare two groups of PD patients. Both groups had cognitive deficits severe enough to justify diagnosis of dementia, but they differed according to caregivers' rating on ADL dysfunction. Parameters which differed between the two groups were interpreted to affect the caregivers' perception of ADL dysfunction in PD patients with cognitive impairment indicative of Parkinson's disease dementia. METHODOLOGY/PRINCIPAL FINDINGS: Thirty of 131 Parkinson's disease patients fulfilled the Movement Disorders Society Task Force - recommended, cognitive Level-I-criteria for dementia. According to standardized caregiver ratings, volunteers were grouped into 18 patients with (ADL- and 12 without instrumental activities of daily living dysfunction (ADL+. Caregiver activities of daily living function ratings closely correlated with self-estimates of patients and those of physician (p<0.001. ADL- patients performed worse on tests assessing visual-construction (p<0.05 and attention (p=0.03 than ADL+ patients. Moreover, the postural instability and gait disorder subtype was more frequent in ADL- patients (p=0.009. ADL- patients tended to have more communication problems (p=0.05, more anxiety (p=0.05 and showed a tendency to be treated more often with neuroleptics (p=0.049 than ADL+. CONCLUSIONS/SIGNIFICANCE: Results indicate that worse attention, visual-construction abilities, the postural instability and gait disorder subtype, communication problems, medication and presence of anxiety are related to activities of daily living dysfunctions in Parkinson's disease patients with cognitive decline indicative of dementia. Our data suggests that not only cognitive factors but also non-cognitive factors seem to be linked to the diagnosis of Parkinson's disease dementia associated with

  11. Key factors for a high-quality peritoneal dialysis program--the role of the PD team and continuous quality improvement.

    Science.gov (United States)

    Fang, Wei; Ni, Zhaohui; Qian, Jiaqi

    2014-06-01

    The proportion of end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) has increased very fast in China over the last decade. Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine, is a recognized high-quality PD unit with a high PD utilization rate, excellent patient and technique survival (1-year and 5-year patient survival rate of 93% and 71%, and 1-year and 5-year technique survival of 96% and 82%, respectively), low peritonitis rate and a well-documented good quality of life of the treated patients. We believe that a dedicated and experienced PD team, a structured patient training program, continuous patient support, establishing and utilizing standardized protocols, starting PD with low dialysis dose, monitoring key performance indicators (KPIs), and continuous quality improvement (CQI) are the key factors underlying this successful PD program. Copyright © 2014 International Society for Peritoneal Dialysis.

  12. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

    Science.gov (United States)

    Dirix, Luc Y; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E; Somer, Robert; Smakal, Martin; Emens, Leisha A; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja; Grote, Hans Juergen; Chin, Kevin; Hamilton, Erika P

    2018-02-01

    Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

  13. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

    OpenAIRE

    Dirix, Luc Y.; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E.; Somer, Robert; Smakal, Martin; Emens, Leisha A.; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja

    2017-01-01

    Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 week...

  14. Effective anti-PD-1 therapy in a SUFU-mutated patient with Gorlin-Goltz syndrome.

    Science.gov (United States)

    Moreira, A; Kirchberger, M C; Toussaint, F; Erdmann, M; Schuler, G; Heinzerling, L

    2018-03-30

    We present a case of a 77-year-old male patient with more than 50 basal cell carcinomas on the head and upper trunk. The patient did not respond to several lines of treatment, including surgery, imiquimod, retinoids, itraconazole and therapy with the hedgehog inhibitor vismodegib. The patient responded well to an off-label therapy with the anti-PD-1 antibody pembrolizumab after 4 infusions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Strategies for the optimal timing to start renal replacement therapy in critically ill patients with acute kidney injury.

    Science.gov (United States)

    Bagshaw, Sean M; Wald, Ron

    2017-05-01

    Renal replacement therapy (RRT) is increasingly utilized to support critically ill patients with severe acute kidney injury (AKI). The question of whether and when to start RRT for a critically ill patient with AKI has long troubled clinicians. When severe complications of AKI develop, the need to commence RRT is unambiguous. In the absence of such complications but in the presence of severe AKI, the optimal time and thresholds for starting RRT are uncertain. The majority of existing data have largely been derived from observational studies. These have been limited due to confounding by indication, considerable heterogeneity in case mix and illness severity, and variably applied definitions for both AKI and for how "timing" was anchored relative to starting RRT. It is unclear whether a preemptive or earlier strategy of RRT initiation aimed largely at avoiding complications related to AKI or a more conservative strategy where RRT is started in response to developing complications leads to better patient-centered outcomes and health services use. This question has been the focus of 2 recently completed randomized trials. In this review, we provide an appraisal of available evidence, discuss existing knowledge gaps, and provide perspective on future research that will better inform the optimal timing of RRT initiation in AKI. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  16. SPECT image analysis using SPM in patients with parkinson's disease and essential tremor : rCBF correlates of immediate surgical outcome following unilateral thalamo-pallidotomy in PD

    International Nuclear Information System (INIS)

    Kim, Jong Ho; Kim, Nam Bum; Lee, Uhn

    2002-01-01

    This study investigated alterations in regional cerebral blood flow (rCBF) in patients with PD and essential tremor (ET) using statistical parametric mapping (SPM) and rCBF correlates of immediate surgical outcome following unilateral thalamo-pallidotomy in patients with PD. Noninvasive rCBF measurements using 99m Tc-ethyl cysteinate dimer (ECD) SPECT were performed on 10 PD (60.5±8.7), 10 ET (55.5±17.7) patients and 10 healthy controls (56.2±12.0). Eight patients with PD following unilateral right thalamo-pallidotomy and five following unilateral left thalamo-pallidotomy underwent pre- and post-operative rCBF SPECT both one week before and after surgery. Acquisition were acquired within 30 min, 360 rotations with 90 projections were collected in a 128 x 128 matrix using a dual head gamma camera (Siemens, Multispect II). Data were analyzed using SPM 99. We found definite bilateral decreased rCBF in perfrontal cortex, bilateral increased rCBF in dentate nucleus of superomedial cerebellum in patients with PD and bilateral increased rCBF in lateral aspect of cerebellum in ET, respectively, compared with healthy controls. In addition, rCBF suspiciousely increased bilaterally in left dorsolateral frontal cortex in ET with equivocal clinical significance. Following 8 right and 5 left unilateral thalamo-pallidotomy in PD patients, immediate postop declines in ipsilateral fronto-temporal and temporal cortical perfusion, respectively, as well as pallidothalamic hypoperfusion were significant. SPM analysis showed that significantly decreased rCBF in bilateral perfrontal cortex and increased rCBF in dentate uncleus of superomedial cerebellum in PD and increased bilateral rCBF in lateral aspect of cerebellum in ET. Unilateral thalamo-pallidotomy in PD patients reduced the immediate post-operative rCBF declines in ipsilateral temporal (frontal) cortex as well as pallidothalamic hypoperfusion which is suggestive of thalamo-cortical diaschisis

  17. Factors influencing access to education, decision making, and receipt of preferred dialysis modality in unplanned dialysis start patients

    DEFF Research Database (Denmark)

    Machowska, Anna; Alscher, Mark Dominik; Vanga, Satyanarayana Reddy

    2016-01-01

    for patients receiving education, making a decision, and receiving their preferred modality choice in UPS patients following a UPS educational program (UPS-EP). Methods: The Offering Patients Therapy Options in Unplanned Start (OPTiONS) study examined the impact of the implementation of a specific UPS......-EP, including decision support tools and pathway improvement on dialysis modality choice. Linear regression models were used to examine the factors predicting three key steps: referral and receipt of UPS-EP, modality decision making, and actual delivery of preferred modality choice. A simple economic assessment...... was performed to examine the potential benefit of implementing UPS-EP in terms of dialysis costs. Results: The majority of UPS patients could receive UPS-EP (214/270 patients) and were able to make a decision (177/214), although not all patients received their preferred choice (159/177). Regression analysis...

  18. Perioperative alimentation in pediatric patients: when to stop, when to start, and what to give.

    Science.gov (United States)

    Broadman, L M

    1999-02-01

    The first steps to liberalize NPO guidelines began in the early 1980s and were based more on compassion than science. Infants were allowed to be awakened at 0300 and given clear liquids. Children whose anticipated surgical start times were later than 1200 were allowed to consume clear liquids at 0500. Fortunately, during the past decade, prospective double-blind NPO studies have been performed to provide more scientific input into the development of more humane and rational pediatric NPO guidelines. In this article the author reviews the historical aspects of aspiration pneumonitis, describes the significant findings of recent landmark studies, and presents the NPO guidelines recently promulgated by the Canadian Anaesthetists' Society.

  19. Guidelines to start enzyme replacement therapy in classic Fabry Disease patients in Latin America

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2017-01-01

    Full Text Available Introduction: Fabry disease is a rare inherited X-linked disorder resulting from the absence or deficient activity of the α-galactosidase A enzyme. Objetive: To provide the first guideline on the best time to start enzyme replacement therapy to treat classic Fabry disease, based on the knowledge and experience of experts from ten Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Mexico, Peru, Uruguay and Venezuela. Methods: The project coordinator designed a survey based on the criteria for starting the treatment which are established in different international guidelines published to date. This document was later sent to all the participants for its evaluation. Results: Fifty experts responded to the survey, whose criteria was divided into 5 sections according to specialty, and they arrived at a consensus. Discussion: The criteria for an early treatment were defined given the growing evidence of a better response and prognosis associated with it. Conclusion: We believe that the importance of this guideline relies on the participation of experts from ten Latin American countries. However, as it deals with a systemic disease whose physiopathological mechanisms and complications are still being described, some manifestations have not been included in the criteria, making it necessary to revise this guideline in order to report any changes that may arise in the future.

  20. Interval Between Hysterectomy and Start of Radiation Treatment Is Predictive of Recurrence in Patients With Endometrial Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cattaneo, Richard [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Hanna, Rabbie K. [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States); Jacobsen, Gordon [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States)

    2014-03-15

    Purpose: Adjuvant radiation therapy (RT) has been shown to improve local control in patients with endometrial carcinoma. We analyzed the impact of the time interval between hysterectomy and RT initiation in patients with endometrial carcinoma. Methods and Materials: In this institutional review board-approved study, we identified 308 patients with endometrial carcinoma who received adjuvant RT after hysterectomy. All patients had undergone hysterectomy, oophorectomy, and pelvic and para-aortic lymph node evaluation from 1988 to 2010. Patients' demographics, pathologic features, and treatments were compared. The time interval between hysterectomy and the start of RT was calculated. The effects of time interval on recurrence-free (RFS), disease-specific (DSS), and overall survival (OS) were calculated. Following univariate analysis, multivariate modeling was performed. Results: The median age and follow-up for the study cohort was 65 years and 72 months, respectively. Eighty-five percent of the patients had endometrioid carcinoma. RT was delivered with high-dose-rate brachytherapy alone (29%), pelvic RT alone (20%), or both (51%). Median time interval to start RT was 42 days (range, 21-130 days). A total of 269 patients (74%) started their RT <9 weeks after undergoing hysterectomy (group 1) and 26% started ≥9 weeks after surgery (group 2). There were a total of 43 recurrences. Tumor recurrence was significantly associated with treatment delay of ≥9 weeks, with 5-year RFS of 90% for group 1 compared to only 39% for group 2 (P<.001). On multivariate analysis, RT delay of ≥9 weeks (P<.001), presence of lymphovascular space involvement (P=.001), and higher International Federation of Gynecology and Obstetrics grade (P=.012) were independent predictors of recurrence. In addition, RT delay of ≥9 weeks was an independent significant predictor for worse DSS and OS (P=.001 and P=.01, respectively). Conclusions: Delay in administering adjuvant RT after

  1. Potentially inappropriate prescribing in institutionalised older patients in Spain: the STOPP-START criteria compared with the Beers criteria

    Directory of Open Access Journals (Sweden)

    Bonet M

    2012-06-01

    Full Text Available Objective: The aims of this study were to identify potentially inappropriate prescribing using the Beers and STOPP criteria. The START criteria were applied to detect prescription omission in the geriatric population. We compared the utility of these criteria in institutionalised older people.Methods: Descriptive study reviewing the medication and clinical records of 81 residents (aged 65 years and more by pharmacists in a nursing home in the Lleida region (Spain.Results: The mean patients’ age was 84 (SD=8 years, with an average of 5 drugs per resident (total prescriptions: 416 medicines. The Beers criteria identified potentially inappropriate medication use in 25% of patients and 48% of patients used at least 1 inappropriate medication according to STOPP criteria. The most frequent potentially inappropriate medications for both criteria were long-acting benzodiazepines and NSAIDs. START detected 58 potential prescribing omissions in 44% of patients. Calcium-vitamin D supplementation in osteoporosis was the most frequent rule (15%, but omissions corresponding to the cardiovascular system implied 23% of patients.Conclusion: The STOPP-START criteria reveal that potentially inappropriate prescribing (PIP is a highly prevalent problem among Spanish nursing home residents, and a statistically significant positive correlation was found between the number of medicines prescribed and the number of PIP detected in this study. The STOPP criteria detect a larger number of PI medications in this geriatric population than the Beers criteria. The prescribing omissions detected by the START criteria are relevant and require intervention. Pharmacists’ review of medications may help identify potentially inappropriate prescribing and, through an interdisciplinary approach, working with physicians may improve prescribing practices among geriatric residents of nursing homes.

  2. Factors influencing access to education, decision making, and receipt of preferred dialysis modality in unplanned dialysis start patients.

    Science.gov (United States)

    Machowska, Anna; Alscher, Mark Dominik; Reddy Vanga, Satyanarayana; Koch, Michael; Aarup, Michael; Qureshi, Abdul Rashid; Lindholm, Bengt; Rutherford, Peter A

    2016-01-01

    Unplanned dialysis start (UPS) leads to worse clinical outcomes than planned start, and only a minority of patients ever receive education on this topic and are able to make a modality choice, particularly for home dialysis. This study aimed to determine the predictive factors for patients receiving education, making a decision, and receiving their preferred modality choice in UPS patients following a UPS educational program (UPS-EP). The Offering Patients Therapy Options in Unplanned Start (OPTiONS) study examined the impact of the implementation of a specific UPS-EP, including decision support tools and pathway improvement on dialysis modality choice. Linear regression models were used to examine the factors predicting three key steps: referral and receipt of UPS-EP, modality decision making, and actual delivery of preferred modality choice. A simple economic assessment was performed to examine the potential benefit of implementing UPS-EP in terms of dialysis costs. The majority of UPS patients could receive UPS-EP (214/270 patients) and were able to make a decision (177/214), although not all patients received their preferred choice (159/177). Regression analysis demonstrated that the initial dialysis modality was a predictive factor for referral and receipt of UPS-EP and modality decision making. In contrast, age was a predictor for referral and receipt of UPS-EP only, and comorbidity was not a predictor for any step, except for myocardial infarction, which was a weak predictor for lower likelihood of receiving preferred modality. Country practices predicted UPS-EP receipt and decision making. Economic analysis demonstrated the potential benefit of UPS-EP implementation because dialysis modality costs were associated with modality distribution driven by patient preference. Education and decision support can allow UPS patients to understand their options and choose dialysis modality, and attention needs to be focused on ensuring equity of access to educational

  3. Physical and psychosocial support requirements of 1,500 patients starting radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kirchheiner, K.; Czajka, A.; Luetgendorf-Cacig, C.; Schmid, M.P.; Komarek, E.; Poetter, R. [Medical Univ. of Vienna, Comprehensive Cancer Center, Vienna (Austria). Dept. of Radiation Oncology; Ponocny-Seliger, E. [Sigmund Freud Private Univ. Vienna (Austria). Dept. of Psychology; Doerr, W. [Medical Univ. of Vienna, Comprehensive Cancer Center, Vienna (Austria). Dept. of Radiation Oncology; Medical Univ. of Vienna (Austria). Christian Doppler Lab. for Medical Radiation Research for Radiation Oncology

    2013-05-15

    Background. The need for psychosocial support in cancer patients is estimated in the literature at 14-50%. At the Department of Radiation Oncology, Medical University of Vienna, approximately 3,000 patients are seen annually. Due to limited staff resources, highly distressed patients need to be selected for focused support. A multidisciplinary screening questionnaire covering physical, social and psychological problems and needs was successfully implemented in clinical routine. We present the results of a representative sample of 1,500 heterogeneous cancer patients before beginning radiotherapy. Patients and methods. The prevalence rates of physical, social and psychological problems and needs were evaluated. Independent risk factors for critical psychological distress were analyzed in a multivariate logistic regression model, in order to identify vulnerable subgroups for focused psychosocial support. Results. Critical psychological distress was found in 22% of the overall cohort, of whom only 26% reported a need for psychological information. Clinically relevant pain was suffered by 31%. Patients' most frequent complaints were weakness, sleeping difficulties and exhaustion. Consequently, 40% were impaired in activities and 35% reported a requirement for support in daily life. A need for further information was expressed by 37% of patients. Significant risk factors for critical psychological distress included pain, functional status, support requirements and patient-reported symptoms. Differences in tumor type, metastases and sociodemographic variables had no impact on critical psychological distress. Conclusion. Approximately one third of all patients beginning radiotherapy have physical, social and psychological problems and should receive focused psychosocial support. Multivariate analysis reveals that patients with impaired ''physical integrity'' are at a significantly higher risk of experiencing critical psychological distress. (orig.)

  4. Physical and psychosocial support requirements of 1,500 patients starting radiotherapy

    International Nuclear Information System (INIS)

    Kirchheiner, K.; Czajka, A.; Luetgendorf-Cacig, C.; Schmid, M.P.; Komarek, E.; Poetter, R.; Ponocny-Seliger, E.; Doerr, W.; Medical Univ. of Vienna

    2013-01-01

    Background. The need for psychosocial support in cancer patients is estimated in the literature at 14-50%. At the Department of Radiation Oncology, Medical University of Vienna, approximately 3,000 patients are seen annually. Due to limited staff resources, highly distressed patients need to be selected for focused support. A multidisciplinary screening questionnaire covering physical, social and psychological problems and needs was successfully implemented in clinical routine. We present the results of a representative sample of 1,500 heterogeneous cancer patients before beginning radiotherapy. Patients and methods. The prevalence rates of physical, social and psychological problems and needs were evaluated. Independent risk factors for critical psychological distress were analyzed in a multivariate logistic regression model, in order to identify vulnerable subgroups for focused psychosocial support. Results. Critical psychological distress was found in 22% of the overall cohort, of whom only 26% reported a need for psychological information. Clinically relevant pain was suffered by 31%. Patients' most frequent complaints were weakness, sleeping difficulties and exhaustion. Consequently, 40% were impaired in activities and 35% reported a requirement for support in daily life. A need for further information was expressed by 37% of patients. Significant risk factors for critical psychological distress included pain, functional status, support requirements and patient-reported symptoms. Differences in tumor type, metastases and sociodemographic variables had no impact on critical psychological distress. Conclusion. Approximately one third of all patients beginning radiotherapy have physical, social and psychological problems and should receive focused psychosocial support. Multivariate analysis reveals that patients with impaired ''physical integrity'' are at a significantly higher risk of experiencing critical psychological distress. (orig.)

  5. [Assessment of factors associated with patients' comprehension of treatment at the start of antiretroviral therapy].

    Science.gov (United States)

    Braga Ceccato, Maria das Graças; Acurcio, Francisco de Assis; Vallano, Antonio; Comini César, Cibele; Crosland Guimarães, Mark Drew

    2009-01-01

    The aim of this study was to evaluate factors associated with patients' comprehension of antiretroviral therapy (ART). Cross-sectional analysis in which patients at 2 HIV/AIDS public referral centers (Belo Horizonte, Brazil) were interviewed after initiating ART. Information was recorded on variables related to the patient's characteristics, the treatment prescribed, and the healthcare professional involved. A score indicating the patients' level of comprehension regarding the medications prescribed was obtained using a latent trait model estimated by the item response theory. A total of 406 patients were interviewed. Mean (SD) age was 35 (10) years, 227 were men (56%), 302 of Afro-American ethnicity (77%), and 213 had education (53%). The regression model determined that 52.25% of the variability of comprehension was explained by the individual's characteristics. Variables associated (Peducation (tablets, and the ART regimen prescribed. Comprehension of information about the ART regimen prescribed varies considerably between individuals. Nonetheless, several factors were found to be associated with the level of understanding: characteristics of the patient (education, clinical severity), characteristics of treatment (daily number of tablets, ART regimen prescribed), and contribution of healthcare professionals (information from physicians and pharmacists). Strategies to reinforce information about ART should be a priority for patients with a low level of understanding.

  6. Testing the START Triage Protocol: Can It Improve the Ability of Nonmedical Personnel to Better Triage Patients During Disasters and Mass Casualties Incidents ?

    Science.gov (United States)

    Badiali, Stefano; Giugni, Aimone; Marcis, Lucia

    2017-06-01

    START (Simple Triage and Rapid Treatment) triage is a tool that is available even to nonmedical rescue personnel in case of a disaster or mass casualty incident (MCI). In Italy, no data are available on whether application of the START protocol could improve patient outcomes during a disaster or MCI. We aimed to address whether "last-minute" START training of nonmedical personnel during a disaster or MCI would result in more effective triage of patients. In this case-control study, 400 nonmedical ambulance crew members were randomly assigned to a non-START or a START group (200 per group). The START group received last-minute START training. Each group examined 6000 patients, obtained from the Emergo Train System (ETS Italy, Bologna, Italy) victims database, and assigned patients a triage code (black-red-yellow-green) along with a reason for the assignment. Each rescuer triaged 30 patients within a 30-minute time frame. Results were analyzed according to Fisher's exact test for a P valueSTART group completed the evaluations in 15 minutes, whereas the non-START group took 30 minutes. The START group correctly triaged 94.2% of their patients, as opposed to 59.83% of the non-START group (PSTART group versus 13.67% and 26.5% for the non-START group. The non-START group had 458 "preventable deaths" on 6000 cases because of incorrect triage, whereas the START group had 91. Even a "last-minute" training on the START triage protocol allows nonmedical personnel to better identify and triage the victims of a disaster or MCI, resulting in more effective and efficient medical intervention. (Disaster Med Public Health Preparedness. 2017;11:305-309).

  7. Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation patient carrying a KCNA5 p.D322H mutation

    DEFF Research Database (Denmark)

    Mora, Cristina; Serzanti, Marialaura; Giacomelli, Alessio

    2017-01-01

    . To investigate the molecular mechanisms underlying AF, we reprogrammed to pluripotency polymorphonucleated leukocytes isolated from the blood of a patient carrying a KCNA5 p.D322H mutation, using a commercially available non-integrating system. The generated iPSCs expressed pluripotency markers...... and differentiated toward cells belonging to the three embryonic germ layers. Moreover, the cells showed a normal karyotype and retained the p.D322H mutation....

  8. One- and 2-Year Mortality Prediction for Patients Starting Chronic Dialysis

    Directory of Open Access Journals (Sweden)

    Mikko Haapio

    2017-11-01

    Discussion: Mortality prediction algorithms could be more widely implemented into management of ESRD patients. The presented models are practical with only a limited number of variables and fairly good performance.

  9. Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Costagliola, Dominique

    2009-01-01

    OBJECTIVE: We examined survival and prognostic factors of patients who developed HIV-associated non-Hodgkin lymphoma (NHL) in the era of combination antiretroviral therapy (cART). DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. METHODS: We included all cART-naive patients......-seven patients (72%) from 22 cohorts met inclusion criteria. Survival at 1 year was 66% [95% confidence interval (CI) 63-70%] for systemic NHL (n = 763) and 54% (95% CI: 43-65%) for primary brain lymphoma (n = 84). Risk factors for death included low nadir CD4 cell counts and a history of injection drug use...... with primary brain lymphoma. More advanced immunodeficiency is the dominant prognostic factor for mortality in patients with HIV-related NHL....

  10. Starting on haemodialysis: a qualitative study to explore the experience and needs of incident patients.

    Science.gov (United States)

    Lai, Alden Yuanhong; Loh, Angela Ping Ping; Mooppil, Nandakumar; Krishnan, Deby Sarojiuy Pala; Griva, Konstadina

    2012-01-01

    Dialysis can be very stressful with the initial months onto treatment being highly critical in terms of both adaptation and mortality. This qualitative study aimed to explore the lived experiences of incident haemodialysis patients in Singapore. Topics related to the end-stage renal disease diagnosis and haemodialysis treatment were raised with 13 incident haemodialysis patients in the form of semi-structured interviews, and interpretative phenomenological analysis was undertaken as the framework for data analysis. Emotional distress, treatment-related concerns and social support emerged as main issues following a critical review of themes. Our study revealed that incident haemodialysis patients have emotional and informational needs, highlighting the importance of intervention programmes in particular to this patient group to promote better psychosocial adjustment to the disease and its treatment.

  11. Predictive Factors of One-Year Mortality in a Cohort of Patients Undergoing Urgent-Start Hemodialysis.

    Directory of Open Access Journals (Sweden)

    Luciene P Magalhães

    Full Text Available Chronic kidney disease (CKD affects 10-15% of adult population worldwide. Incident patients on hemodialysis, mainly those on urgent-start dialysis at the emergency room, have a high mortality risk, which may reflect the absence of nephrology care. A lack of data exists regarding the influence of baseline factors on the mortality of these patients. The aim of this study was to evaluate the clinical and laboratory characteristics of this population and identify risk factors that contribute to their mortality.We studied 424 patients who were admitted to our service between 01/2006 and 12/2012 and were followed for 1 year. We analyzed vascular access, risk factors linked to cardiovascular disease (CVD and mineral and bone disease associated with CKD (CKD-MBD, and clinical events that occurred during the follow-up period. Factors that influenced patient survival were evaluated by Cox regression analysis.The patient mean age was 50 ± 18 years, and 58.7% of them were male. Hypertension was the main cause of primary CKD (31.8%. Major risk factors were smoking (19.6%, dyslipidemia (48.8%, and CVD (41%. Upon admission, most patients had no vascular access for hemodialysis (89.4%. Biochemical results showed that most patients were anemic with high C-reactive protein levels, hypocalcemia, hyperphosphatemia, elevated parathyroid hormone and decreased 25-hydroxy vitamin D. At the end of one year, 60 patients died (14.1%. These patients were significantly older, had a lower percentage of arteriovenous fistula in one year, and low levels of 25-hydroxy vitamin D.The combined evaluation of clinical and biochemical parameters and risk factors revealed that the mortality in urgent-start dialysis is associated with older age and low levels of vitamin D deficiency. A lack of a permanent hemodialysis access after one year was also a risk factor for mortality in this population.

  12. Predictors of delay in starting radiation treatment for patients with early stage breast cancer

    International Nuclear Information System (INIS)

    Benk, Veronique; Ho, Vivian; Fortin, Paul R.; Zhang, G.; Levinton, Carey; Freeman, C.R.

    1998-01-01

    Purpose: To describe the factors predicting waiting time for radiation treatment in early breast cancer. Materials and Methods: Between January 1992 and December 1993, 739 patients with Stage I and II breast cancer were treated with conservative treatment at three McGill University Hospitals. Waiting time was defined as the interval between the date of surgery and the date of the first radiation treatment. Delay was defined as a waiting time of more than 7 weeks for women who did not receive chemotherapy (Group NC, n 478), and as a waiting time of more than 24 weeks for those who received chemotherapy (Group C, n = 261). We analyzed predictive factors related to the patient (age, stage, treatment on protocol, income by postal code) and to the referring hospital (university or community hospital). Results: For the entire population, 54% of patients were delayed, 72% in Group NC and 21.4% in Group C. Univariate analysis showed an impact of referring hospital in both groups, and of stage and treatment on protocol in Group C (all p = 0.001). Multivariate analysis showed that delays were significantly less in Group NC for women referred from a community hospital (p = 0.001) and in Group C for women with Stage I disease (p = 0.06), those treated on protocol, and those referred from a university hospital (p = 0.001). Conclusion: More than half of patients with early breast cancer waited more than the recommended intervals for radiation therapy. However, lower income breast cancer patients did not wait longer for treatment than higher income patients, possibly a result of the Canadian Medicare system which provides universal access to health care

  13. Dietary resilience in patients with severe COPD at the start of a pulmonary rehabilitation program

    NARCIS (Netherlands)

    Ter Beek, Lies; van der Vaart, Hester; Wempe, Johan B; Dzialendzik, Aliaksandra O; Roodenburg, Jan Ln; van der Schans, Cees P; Keller, Heather H; Jager-Wittenaar, Harriët

    2018-01-01

    Background: COPD may impact food-related activities, such as grocery shopping, cooking, and eating. Decreased food intake may result in an unhealthy diet, and in malnutrition, which is highly prevalent in patients with COPD. Malnutrition is known to negatively impact clinical outcome and quality of

  14. Antiretroviral Treatment-Associated Tuberculosis in a Prospective Cohort of HIV-Infected Patients Starting ART

    Directory of Open Access Journals (Sweden)

    William Worodria

    2011-01-01

    Full Text Available Commencement of antiretroviral treatment (ART in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4% patients were diagnosed with TB during followup. Eight (3.8% patients had ART-associated TB (incidence rate of 4.3 per 100 person years; of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years. A body mass index of less than 18.5 kg/m2 BMI (HR 5.85 95% CI 1.24–27.46, P=.025 and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36–38.33, P=.020 were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray, the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence.

  15. Persistence of pharmacological treatment into adulthood, in UK primary care, for ADHD patients who started treatment in childhood or adolescence

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    McCarthy Suzanne

    2012-12-01

    Full Text Available Abstract Background ADHD guidelines in the UK suggest that children and adults who respond to pharmacological treatment should continue for as long as remains clinically effective, subject to regular review. To what extent patients persist with treatment from childhood and adolescence into adulthood is not clear. This study aims to describe, in UK primary care, the persistence of pharmacological treatment for patients with ADHD who started treatment aged 6–17 years and to estimate the percentage of patients who continued treatment from childhood and adolescence into adulthood. Methods The Health Improvement Network (THIN database was used to identify patients with ADHD who received their first prescription for methylphenidate/ dexamfetamine/atomoxetine, aged 6–17 years. Patients were monitored until their ‘censored date’ (the earliest of the following dates: date the last prescription coded in the database ended, end of the study period (31st December 2008, date at which they transferred out of their practice, date of death, the last date the practice contributed data to the database. Persistence of treatment into adulthood was estimated using Kaplan Meier analysis. Results 610 patients had follow-up data into adulthood. 213 patients (93.4% male started treatment between 6–12 years; median treatment duration 5.9 years. 131 (61.5% stopped before 18 years, 82 (38.5% were still on treatment age ≥18 years. 397 patients (86.4% male started treatment between 13–17 years; median treatment duration was 1.6 years. 227 (57.2% stopped before 18 years, 170 (42.8% were still on treatment age ≥18 years. The number of females in both age categories was too small to formally test for differences between genders in persistence of treatment. Conclusion Persistence of treatment into adulthood is lower (~40% compared with published rates of persistence of the condition (~65% when symptomatic definition of remission used. Due to the limited number of

  16. Is the decline of renal function different before and after the start of dialysis?

    NARCIS (Netherlands)

    de Jager, Dinanda J.; Halbesma, Nynke; Krediet, Raymond T.; Boeschoten, Elisabeth W.; le Cessie, Saskia; Dekker, Friedo W.; Grootendorst, Diana C.; Apperloo, A. J.; Bijlsma, J. A.; Boekhout, M.; Boer, W. H.; van der Boog, P. J. M.; Büller, H. R.; van Buren, M.; de Charro, F. Th; Doorenbos, C. J.; van den Dorpel, M. A.; van Es, A.; Fagel, W. J.; Feith, G. W.; de Fijter, C. W. H.; Frenken, L. A. M.; van Geelen, J. A. C. A.; Gerlag, P. G. G.; Grave, W.; Gorgels, J. P. M. C.; Huisman, R. M.; Jager, K. J.; Jie, K.; Koning-Mulder, W. A. H.; Koolen, M. I.; Hovinga, T. K. Kremer; Lavrijssen, A. T. J.; Luik, A. J.; van der Meulen, J.; Parlevliet, K. J.; Raasveld, M. H. M.; van der Sande, F. M.; Schonck, M. J. M.; Schuurmans, M. M. J.; Siegert, C. E. H.; Stegeman, C. A.; Stevens, P.; Thijssen, J. G. P.; Valentijn, R. M.; Vastenburg, G. H.; Verburgh, C. A.; Vincent, H. H.; Vos, P. F.

    2013-01-01

    The presence of glomerular filtration in dialysis patients is associated with improved survival and quality of life. This study explores the time course of the glomerular filtration rate (GFR) between 1 year before and 1 year after the start of haemodialysis (HD) and peritoneal dialysis (PD). This

  17. The Exosomal/Total α-Synuclein Ratio in Plasma Is Associated With Glucocerebrosidase Activity and Correlates With Measures of Disease Severity in PD Patients

    Directory of Open Access Journals (Sweden)

    Silvia Cerri

    2018-05-01

    Full Text Available Intensive research efforts in the field of Parkinson’s disease (PD are focusing on identifying reliable biomarkers which possibly help physicians in predicting disease onset, diagnosis, and progression as well as evaluating the response to disease-modifying treatments. Given that abnormal alpha-synuclein (α-syn accumulation is a primary component of PD pathology, this protein has attracted considerable interest as a potential biomarker for PD. Alpha-synuclein can be detected in several body fluids, including plasma, where it can be found as free form or in association with exosomes, small membranous vesicles secreted by virtually all cell types. Together with α-syn accumulation, lysosomal dysfunctions seem to play a central role in the pathogenesis of PD, given the crucial role of lysosomes in the α-syn degradation. In particular, heterozygous mutations in the GBA1 gene encoding lysosomal enzyme glucocerebrosidase (GCase are currently considered as the most important risk factor for PD. Different studies have found that GCase deficiency leads to accumulation of α-syn; whereas at the same time, increased α-syn may inhibit GCase function, thus inducing a bidirectional pathogenic loop. In this study, we investigated whether changes in plasma total and exosome-associated α-syn could correlate with disease status and clinical parameters in PD and their relationship with GCase activity. We studied 39 PD patients (mean age: 65.2 ± 8.9; men: 25, without GBA1 mutations, and 33 age-matched controls (mean age: 61.9 ± 6.2; men: 15. Our results showed that exosomes from PD patients contain a greater amount of α-syn compared to healthy subjects (25.2 vs. 12.3 pg/mL, p < 0.001 whereas no differences were found in plasma total α-syn levels (15.7 vs. 14.8 ng/mL, p = 0.53. Moreover, we highlighted a significant increase of plasma exosomal α-syn/total α-syn ratio in PD patients (1.69 vs. 0.89, p < 0.001, which negatively correlates with disease

  18. Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms.

    Science.gov (United States)

    Alhusseini, M; Samantray, J

    2017-04-01

    Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term. Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months. Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases. Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Implant R100 Predicts Rectal Bleeding in Prostate Cancer Patients Treated with IG-IMRT to 45 Gy and Pd-103 Implant

    OpenAIRE

    Matthew Packard; Vladimir Valakh; Russell Fuhrer

    2014-01-01

    Purpose. To define factors associated with rectal bleeding in patients treated with IG-IMRT followed by Pd-103 seed implant. Methods and Materials. We retrospectively reviewed 61 prostate adenocarcinoma patients from 2002 to 2008. The majority (85.2%) were of NCCN intermediate risk category. All received IG-IMRT to the prostate and seminal vesicles followed by Pd-103 implant delivering a mean D90 of 100.7 Gy. Six patients received 45 Gy to the pelvic nodes and 10 received androgen deprivation...

  20. Drug-resistant tuberculosis among HIV-infected patients starting antiretroviral therapy in Durban, South Africa.

    Directory of Open Access Journals (Sweden)

    Jeffrey K Hom

    Full Text Available To estimate the prevalence of drug-resistant tuberculosis (TB and describe the resistance patterns in patients commencing antiretroviral therapy (ART in an HIV clinic in Durban, South Africa.Cross-sectional cohort study.Consecutive HIV-infected adults (≥ 18y/o initiating HIV care were enrolled from May 2007-May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium. Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed.1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42-150/µl. 267 subjects (26% reported a prior history of TB and 210 (20% were receiving TB treatment at enrollment; 191 (18% subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0-12.4. Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9-30.5 compared to 5.2% (95% CI 2.1-8.9 among those with no prior TB. 5.1% (95% CI 2.4-9.5 had rifampin or rifampin plus INH resistance.The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.

  1. Why START?

    International Nuclear Information System (INIS)

    Mendelsohn, J.

    1991-01-01

    Barring some major unexpected downturn in US-Soviet relations, it seems likely that the long-awaited Strategic Arms Reduction Talks (START) treaty will be signed sometime in 1991. Under negotiation for the past nine years, public acceptance and Senate approval of a START treaty will be facilitated by the generally less confrontational East-West relationship which has evolved over that time, by the growing constraints on the US defense budget, and by the obvious merits of the treaty itself. Not only will the nearly complete START treaty be an extremely useful and powerful arms control agreement, it is also decidedly advantageous to US security interests. First and foremost, a START treaty will cap and reduce the steady buildup of nuclear weapons that has characterized the last 30 years of the US-Soviet strategic relationship. As a result of the basic outline originally agreed to at the Reykjavik summit, START will take a 25 to 35 percent bite out of existing nuclear arsenals, impose approximately a 50 percent cut in overall Soviet ballistic missile warheads and throw-weight (lifting power or payload capacity), and produce an exact 50 percent cut in Soviet SS-18 missiles

  2. Programmed Death Ligand 1 (PD-L1 Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Gerardo Botti

    2017-02-01

    Full Text Available Triple Negative Breast Cancers (TNBC subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1 is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs, to define its real prognostic value, optimizing immunohistochemistry method with an “approved for diagnostic assay” antibody. PD-L1 expression directly correlated with proliferation index (Ki-67, glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan–Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS but not correlated with overall survival (OS. Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC.

  3. PD-L1 Expression of Tumor Cells, Macrophages, and Immune Cells in Non-Small Cell Lung Cancer Patients with Malignant Pleural Effusion.

    Science.gov (United States)

    Tseng, Yen-Han; Ho, Hsiang-Ling; Lai, Chiung-Ru; Luo, Yung-Hung; Tseng, Yen-Chiang; Whang-Peng, Jacqueline; Lin, Yi-Hsuan; Chou, Teh-Ying; Chen, Yuh-Min

    2018-03-01

    Whether immunohistochemical staining of programmed death ligand 1 (PD-L1) on cells of pleural effusion could be used to predict response to immunotherapy treatment has not been reported. We retrospectively enrolled patients who had undergone malignant pleural effusion drainage and had effusion cell block specimens from 2014 to 2016. Immunohistochemical staining for PD-L1 was performed with tumor cells, immune cells, and macrophages of all cell block specimens. Immunoactivity was scored as 0 for absence of staining and 1+ for faint, 2+ for moderate, and 3+ for intense membranous staining. Patients' clinicopathological characteristics were also collected. PD-L1 expression of pleural effusion tumor cells was associated with the PD-L1 expression of macrophages (p = 0.003) and immune cells (p pleural effusion tumor cells and macrophages. The low intensity of PD-L1 expression in immune cells is associated with the poor survival of patients with lung cancer with malignant pleural effusion. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  4. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections.

    Science.gov (United States)

    Tängdén, T; Ramos Martín, V; Felton, T W; Nielsen, E I; Marchand, S; Brüggemann, R J; Bulitta, J B; Bassetti, M; Theuretzbacher, U; Tsuji, B T; Wareham, D W; Friberg, L E; De Waele, J J; Tam, V H; Roberts, Jason A

    2017-07-01

    Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success.

  5. Randomised Controlled Trial to determine the appropriate time to initiate peritoneal dialysis after insertion of catheter to minimise complications (Timely PD study

    Directory of Open Access Journals (Sweden)

    Fassett Robert G

    2010-06-01

    Full Text Available Abstract Background The most appropriate time to initiate dialysis after surgical insertion of Tenckhoff catheters is not clear in the literature. There is the possibility of peritoneal dialysis (PD complications such as leakage and infection if dialysis is started too soon after insertion. However, much morbidity and expense could be saved by reducing dependency on haemodialysis (HD by earlier initiation of PD post catheter insertion. Previous studies are observational and mostly compare immediate with delayed use. The primary objective is to determine the safest and shortest time interval between surgical placement of a Tenckhoff catheter and starting PD. Methods/Design This is a randomised controlled trial of patients who will start PD after insertion of Tenckhoff catheter at Royal Brisbane and Women's Hospital (RBWH or Rockhampton Base Hospital (RBH who meet the inclusion criteria. Patients will be stratified by site and diabetic status. The patients will be randomised to one of three treatment groups. Group 1 will start PD one week after Tenckhoff catheter insertion, group 2 at two weeks and group 3 at four weeks. Nurses and physicians will be blinded to the randomised allocation. The primary end point is the complication rate (leaks and infection after initiation of PD. Discussion The study will determine the most appropriate time to initiate PD after placement of a Tenckhoff catheter. Trial Registration ACTRN12610000076077

  6. Starting out

    NARCIS (Netherlands)

    Ans Merens; Freek Bucx

    2018-01-01

    Original title: Werken aan de start Women in the Netherlands have been outperforming men in education for many years now. However, this superior educational achievement does not translate into a better position on the labour market. More women work today than in the past, but still fewer than men.

  7. A Radiation Badge Survey for Family Members Living With Patients Treated With a 103Pd Permanent Breast Seed Implant

    International Nuclear Information System (INIS)

    Keller, Brian M.; Pignol, Jean-Philippe; Rakovitch, Eileen; Sankreacha, Raxa; O'Brien, Peter

    2008-01-01

    Purpose: Sixty-seven patients with early-stage breast cancer were treated in a Phase I/II clinical trial using a 103 Pd permanent breast seed implant as adjuvant radiotherapy after breast-conserving surgery. We report the dose received by family members living with these patients and compare measured doses with theoretical worst-case scenario estimates. Methods and Materials: Exposure-rate measurements were taken at 1 m from the patient by using a calibrated low-energy survey meter. Landauer (Landauer Inc., Glenwood, IL) Luxel badges, with sensitivity of 0.01 mSv, were given to family members to wear after the implantation. Badge readings for 33 spouses and 28 other family members were used to estimate effective doses, and these were compared with theory. Results: Average preimplantation planning target volume from computed tomography was 50.3 ml (range, 18.0-96.7 ml), and average preimplantation distance between the skin and the most anterior planning target volume margin was 0.57 cm. The average maximum exposure rate was measured to be 2.4 ± 1.1 mR/h, and average measured dose to a spouse was 0.99 ± 1.0 mSv. The calculated exposure rates and spousal doses using preimplantation computed tomography scan data overestimated those measured. Average measured family member dose (excluding spouses) was 0.20 ± 0.58 mSv. Conclusions: Based on measured and calculated spousal doses, a permanent breast seed implant using 103 Pd is safe for the public. However, it is recommended that extra precautions in the way of a breast patch be used when patients with an implant will be in the vicinity of toddlers or pregnant women

  8. PD Lab

    NARCIS (Netherlands)

    Bilow, Marcel; Entrop, Alexis Gerardus; Lichtenberg, Jos; Stoutjesdijk, Pieter

    2015-01-01

    PD Lab explores the applications of building sector related product development. PD lab investigates and tests digital production technologies like CNC milled wood connections. It will also act as a platform in its wider meaning to investigate the effects and influences of file to factory

  9. FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy

    International Nuclear Information System (INIS)

    Ghebeh, Hazem; Barhoush, Eman; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Dermime, Said

    2008-01-01

    Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T regs ). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T regs as a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated in vitro and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease. Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease. A co-existence of B7-H1 + T lymphocytes and FOXP3 + T regs was evidenced by the highly significant correlation of these molecules (P < .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3 + T regs , B7-H1 + and PD-1 + TIL synergistically correlated with high histological grade (III) (P < .001), estrogen receptor negative status (P = .017), and the presence of severe lymphocytic infiltration (P = .022). Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T regs and B7-H1/PD-1 molecules

  10. PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Zhang Weidong

    2010-11-01

    Full Text Available Abstract Background Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression. Methods PBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1, CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between expression of surface markers and HCV viral load or ALT was studied. Results Declined naïve and increased TEMRA CD8+ T subsets were found in HCV-infected individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+ TEM (p Conclusion PD-1 level on peripheral CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected patients, which made PD-1 a novel indicator to evaluate HCV replication and disease progression in chronic hepatitis C patients.

  11. Press Start

    Science.gov (United States)

    Harteveld, Casper

    This level sets the stage for the design philosophy called “Triadic Game Design” (TGD). This design philosophy can be summarized with the following sentence: it takes two to tango, but it takes three to design a meaningful game or a game with a purpose. Before the philosophy is further explained, this level will first delve into what is meant by a meaningful game or a game with a purpose. Many terms and definitions have seen the light and in this book I will specifically orient at digital games that aim to have an effect beyond the context of the game itself. Subsequently, a historical overview is given of the usage of games with a serious purpose which starts from the moment we human beings started to walk on our feet till our contemporary society. It turns out that we have been using games for all kinds of non-entertainment purposes for already quite a long time. With this introductory material in the back of our minds, I will explain the concept of TGD by means of a puzzle. After that, the protagonist of this book, the game Levee Patroller, is introduced. Based on the development of this game, the idea of TGD, which stresses to balance three different worlds, the worlds of Reality, Meaning, and Play, came into being. Interested? Then I suggest to quickly “press start!”

  12. Overexpression of blood microRNAs 103a, 30b, and 29a in L-dopa-treated patients with PD.

    Science.gov (United States)

    Serafin, Alice; Foco, Luisa; Zanigni, Stefano; Blankenburg, Hagen; Picard, Anne; Zanon, Alessandra; Giannini, Giulia; Pichler, Irene; Facheris, Maurizio F; Cortelli, Pietro; Pramstaller, Peter P; Hicks, Andrew A; Domingues, Francisco S; Schwienbacher, Christine

    2015-02-17

    The aims of the present study were to profile the expression of several candidate microRNAs (miRNAs) in blood from L-dopa-treated and drug-naive patients with Parkinson disease (PD) vs unaffected controls and to interpret the miRNA expression data in a biological context. We analyzed RNAs from peripheral blood of 36 L-dopa-treated, 10 drug-naive patients with PD and unaffected controls matched 1:1 by sex and age. We evaluated expression by reverse transcription-quantitative real-time PCR, and we analyzed data using a 2-tailed paired t test. To detect miRNA targets, several miRNA resources were combined to generate an overall score for each candidate gene using weighted rank aggregation. Significant overexpression of miR-103a-3p (p < 0.0001), miR-30b-5p (p = 0.002), and miR-29a-3p (p = 0.005) in treated patients with PD was observed, and promising candidate target genes for these were revealed by an integrated in silico analysis. We revealed 3 candidate biomarkers for PD. miRNAs 30b-5p and 29a-3p replicated a documented deregulation in PD albeit opposite to published data, while for miR-103a-3p, we demonstrated for the first time an overexpression in treated patients with PD. Expression studies in patients and/or in isolated peripheral blood mononuclear cells before and after L-dopa administration are necessary to define the involvement of L-dopa treatment in the observed overexpression. Our in silico analysis to prioritize targets of deregulated miRNAs identified candidate target genes, including genes related to neurodegeneration and PD. Despite the preliminary character of our study, the results provide a rationale for further clarifying the role of the identified miRNAs in the pathogenesis of PD and for validating their diagnostic potential. © 2015 American Academy of Neurology.

  13. Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.

    Science.gov (United States)

    Lipson, Evan J; Lilo, Mohammed T; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Haiying; Brothers, Patricia; Schollenberger, Megan; Sharfman, William H; Taube, Janis M

    2017-01-01

    Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.

  14. Medicatiescreening met Beers-criteria en STOPP/START-criteria bij de ouedere patient: associatie tussen potentieel ongewenst geneesmiddelengebruik en geneesmiddelgerelateerde ziekenhuisopnamen

    NARCIS (Netherlands)

    Stelt, CAK; Vermeulen Windsant - van der Tweel, AMA; Egberts, ACG; Van Den Bemt, Patricia M L A; Leendertse, AJ; Hermens, W.Th.; van Marum, R.J.; Derijks, H.J.

    2015-01-01

    Medication screening using Beers and stopp/start criteria for elderly patients: association between potentially inappropriate medication and medication-related hospital admissions OBJECTIVE To assess the risk of medication-related hospital admissions associated with inappropriate medication use

  15. Anti-PD-L1 Treatment Induced Central Diabetes Insipidus.

    Science.gov (United States)

    Zhao, Chen; Tella, Sri Harsha; Del Rivero, Jaydira; Kommalapati, Anuhya; Ebenuwa, Ifechukwude; Gulley, James; Strauss, Julius; Brownell, Isaac

    2018-02-01

    Immune checkpoint inhibitors, including anti-programmed cell death protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti-CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade. We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti-PD-L1 monoclonal antibody avelumab and achieved partial response. The patient developed nocturia, polydipsia, and polyuria 3 months after starting avelumab. Further laboratory testing revealed central DI. Avelumab was held and he received desmopressin for the management of central DI. Within 6 weeks after discontinuation of avelumab, the patient's symptoms resolved and he was eventually taken off desmopressin. The patient remained off avelumab and there were no signs or symptoms of DI 2 months after the discontinuation of desmopressin. To our knowledge, this is the first report of central DI associated with anti-PD-L1 immunotherapy. The patient's endocrinopathy was successfully managed by holding treatment with the immune checkpoint inhibitor. This case highlights the importance of early screening and appropriate management of hormonal irAEs in subjects undergoing treatment with immune checkpoint inhibitors to minimize morbidity and mortality. Copyright © 2017 Endocrine Society

  16. to start

    Indian Academy of Sciences (India)

    Click here to start. Table of contents. Slide 1 · Slide 2 · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20 · Slide 21 · Slide 22 · Slide 23 · Slide 24 · Slide 25 · Slide 26 · Slide 27 · Slide 28 · Slide 29 · Slide 30.

  17. Starting electronics

    CERN Document Server

    Brindley, Keith

    2005-01-01

    Starting Electronics is unrivalled as a highly practical introduction for hobbyists, students and technicians. Keith Brindley introduces readers to the functions of the main component types, their uses, and the basic principles of building and designing electronic circuits. Breadboard layouts make this very much a ready-to-run book for the experimenter; and the use of multimeter, but not oscilloscopes, puts this practical exploration of electronics within reach of every home enthusiast's pocket. The third edition has kept the simplicity and clarity of the original. New material

  18. Prevalence of CMMSE defined cognitive impairment among peritoneal dialysis patients and its impact on peritonitis.

    Science.gov (United States)

    Shea, Yat Fung; Lam, Man-Fai; Lee, Mi Suen Connie; Mok, Ming Yee Maggie; Lui, Sing-Leung; Yip, Terence P S; Lo, Wai Kei; Chu, Leung Wing; Chan, Tak-Mao

    2016-02-01

    Peritoneal dialysis (PD) exchange procedure is complex. Patients with cognitive impairment (CI) may require assistance. We studied the prevalence of CI among PD patients, its impact on PD-related peritonitis and the outcome of assisted PD. Cantonese version of Mini-Mental State examination (CMMSE) was performed in 151 patients newly started on PD. Data on patient characteristics including demographics, co-morbidities, blood parameters, medications, and number of PD-related peritonitis in the first 6 months were collected. 151 subjects were recruited. The age of studied patients was 60 ± 15.0 years, and 45% were female. The prevalence of CI was 13.9% using education-adjusted cut-off of CMMSE. Patients older than 65-year-old, female, and lower education level were independent risk factors for CI (OR 9.27 p = 0.001, OR 14.84 p = 0.005, and OR 6.10 p = 0.009, respectively). Age greater than 65-year old is an independent risk factor for PD-related peritonitis but CI was not. Patients requiring assisted PD were of older age (p peritonitis (p = 0.07). CI is common among local PD patients. Overall, CI could not be identified as an independent risk factor for PD peritonitis. There is a higher prevalence of CI among assisted PD patients but helpers may not completely eliminate the risk of PD-related peritonitis.

  19. Epidemiology and Management of Patients With Acute Coronary Syndromes in Contemporary Real-World Practice: Evolving Trends From the EYESHOT Study to the START-ANTIPLATELET Registry.

    Science.gov (United States)

    Calabrò, Paolo; Gragnano, Felice; di Maio, Marco; Patti, Giuseppe; Antonucci, Emilia; Cirillo, Plinio; Gresele, Paolo; Palareti, Gualtiero; Pengo, Vittorio; Pignatelli, Pasquale; Pennacchi, Mauro; Granatelli, Antonino; De Servi, Stefano; De Luca, Leonardo; Marcucci, Rossella

    2018-01-01

    The epidemiology and management of patients with acute coronary syndromes (ACSs) have evolved. We aimed to describe recent demographics and therapeutic changes in the Italian ACS population. We analyzed data from 2 multicenter consecutive Italian registries (the EYESHOT [EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalised in iTalian cardiac care units] and START-ANTIPLATELET registries) enrolling patients with ACS between December 2013 and June 2016. An overall population of 3756 patients with ACS was enrolled: 2585 in the EYESHOT and 1171 in the START-ANTIPLATELET. Compared with the EYESHOT, patients in the START-ANTIPLATELET registry presented more frequently with ST-segment elevation myocardial infarction and were more often smokers and dyslipidemic (all P START-ANTIPLATELET (all P START-ANTIPLATELET compared with the EYESHOT. The START-ANTIPLATELET and EYESHOT registries provide consecutive snapshots in the contemporary management of patients with ACS in Italy, showing important changes in both demographic characteristics and treatment strategies.

  20. Psychometric Properties of the Japanese Version of the STarT Back Tool in Patients with Low Back Pain.

    Science.gov (United States)

    Matsudaira, Ko; Oka, Hiroyuki; Kikuchi, Norimasa; Haga, Yuri; Sawada, Takayuki; Tanaka, Sakae

    2016-01-01

    The STarT Back Tool uses prognostic indicators to classify patients with low back pain into three risk groups to guide early secondary prevention in primary care. The present study aimed to evaluate the psychometric properties of the Japanese version of the tool (STarT-J). An online survey was conducted among Japanese patients with low back pain aged 20-64 years. Reliability was assessed by examining the internal consistency of the overall and psychosocial subscales using Cronbach's alpha coefficients. Spearman's correlation coefficients were used to evaluate the concurrent validity between the STarT-J total score/psychosocial subscore and standard reference questionnaires. Discriminant validity was evaluated by calculating the area under the curves (AUCs) for the total and psychosocial subscale scores against standard reference cases. Known-groups validity was assessed by examining the relationship between low back pain-related disability and STarT-J scores. The analysis included data for 2000 Japanese patients with low back pain; the mean (standard deviation [SD]) age was 47.7 (9.3) years, and 54.1% were male. The mean (SD) STarT-J score was 2.2 (2.1). The Cronbach's alpha coefficient was 0.75 for the overall scale and 0.66 for the psychosocial subscale. Spearman's correlation coefficients ranged from 0.30 to 0.59, demonstrating moderate to strong concurrent validity. The AUCs for the total score ranged from 0.65 to 0.83, mostly demonstrating acceptable discriminative ability. For known-groups validity, participants with more somatic symptoms had higher total scores. Those in higher STarT-J risk groups had experienced more low back pain-related absences. The overall STarT-J scale was internally consistent and had acceptable concurrent, discriminant, and known-groups validity. The STarT-J can be used with Japanese patients with low back pain.

  1. Improvement of Freezing of Gait in Patients with Parkinson's Disease by Imagining Bicycling

    Directory of Open Access Journals (Sweden)

    Akio Kikuchi

    2014-03-01

    Full Text Available Freezing of gait (FOG is one of the factors that reduce the quality of life in patients with Parkinson's disease (PD. Imagining bicycling before gait start provided improvement in FOG in 2 PD patients. Imagining and mimicking bicycling after the initiation of gait allowed the rhythmic gait to continue without interruption. We suggest that imagining and mimicking bicycling, which are nonexternal cues, could serve as a helpful therapeutic approach for the intractable freezing and interruption of gait of PD patients.

  2. Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria.

    LENUS (Irish Health Repository)

    Gallagher, P F

    2011-06-01

    Inappropriate prescribing is particularly common in older patients and is associated with adverse drug events (ADEs), hospitalization, and wasteful utilization of resources. We randomized 400 hospitalized patients aged ≥ 65 years to receive either the usual pharmaceutical care (control) or screening with STOPP\\/START criteria followed up with recommendations to their attending physicians (intervention). The Medication Appropriateness Index (MAI) and Assessment of Underutilization (AOU) index were used to assess prescribing appropriateness, both at the time of discharge and for 6 months after discharge. Unnecessary polypharmacy, the use of drugs at incorrect doses, and potential drug-drug and drug-disease interactions were significantly lower in the intervention group at discharge (absolute risk reduction 35.7%, number needed to screen to yield improvement in MAI = 2.8 (95% confidence interval 2.2-3.8)). Underutilization of clinically indicated medications was also reduced (absolute risk reduction 21.2%, number needed to screen to yield reduction in AOU = 4.7 (95% confidence interval 3.4-7.5)). Significant improvements in prescribing appropriateness were sustained for 6 months after discharge.

  3. PD Lab

    Directory of Open Access Journals (Sweden)

    Marcel Bilow

    2015-08-01

    Full Text Available PD Lab explores the applications of building sector related product development.  PD lab investigates and tests digital production technologies like CNC milled wood connections. It will also act as a platform in its wider meaning to investigate the effects and influences of file to factory production, to explore the potential in the field of sustainability, material use, logistics and the interaction of stakeholders within the chain of the building process.

  4. Emergent Start Peritoneal Dialysis for End-Stage Renal Disease: Outcomes and Advantages.

    Science.gov (United States)

    Nayak, K Shivanand; Subhramanyam, Sreepada V; Pavankumar, Navva; Antony, Sinoj; Sarfaraz Khan, M A

    2018-01-01

    Initiating renal replacement therapy in late referred patients with central venous catheter (CVC) hemodialysis (HD) causes serious complications. In urgent start peritoneal dialysis, initiating peritoneal dialysis (PD) within 14 days of catheter insertion still needs HD with CVC. We initiated Emergent start PD (ESPD) with Automated PD (APD) at our center within 48 h from the time of presentation. A prospective, case-controlled, intention-to-treat study with 56 patients was conducted between March 2016 and August 2017. Group A (24 patients) underwent conventional PD 14 days after catheter insertion. Group B (32 patients), underwent ESPD with APD. Exit site leak (ESL), catheter blockage, and peritonitis at 90 days were primary outcomes. Technique survival was secondary outcome. Baseline characteristics were similar with 3 episodes of ESLs (9.4%) in the study group and none in the control group (p = 0.123). Catheter blockage (16.7%-Group A, 25%-Group B) and peritonitis (none vs. 9.4% in study group) were similar in terms of statistical details just as technique survival (95%-Group A, 88.2%-Group B at 90 days). ESPD with APD in the unplanned patient is an appropriate approach. © 2018 S. Karger AG, Basel.

  5. The property distance index PD predicts peptides that cross-react with IgE antibodies

    Science.gov (United States)

    Ivanciuc, Ovidiu; Midoro-Horiuti, Terumi; Schein, Catherine H.; Xie, Liping; Hillman, Gilbert R.; Goldblum, Randall M.; Braun, Werner

    2009-01-01

    Similarities in the sequence and structure of allergens can explain clinically observed cross-reactivities. Distinguishing sequences that bind IgE in patient sera can be used to identify potentially allergenic protein sequences and aid in the design of hypo-allergenic proteins. The property distance index PD, incorporated in our Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/), may identify potentially cross-reactive segments of proteins, based on their similarity to known IgE epitopes. We sought to obtain experimental validation of the PD index as a quantitative predictor of IgE cross-reactivity, by designing peptide variants with predetermined PD scores relative to three linear IgE epitopes of Jun a 1, the dominant allergen from mountain cedar pollen. For each of the three epitopes, 60 peptides were designed with increasing PD values (decreasing physicochemical similarity) to the starting sequence. The peptides synthesized on a derivatized cellulose membrane were probed with sera from patients who were allergic to Jun a 1, and the experimental data were interpreted with a PD classification method. Peptides with low PD values relative to a given epitope were more likely to bind IgE from the sera than were those with PD values larger than 6. Control sequences, with PD values between 18 and 20 to all the three epitopes, did not bind patient IgE, thus validating our procedure for identifying negative control peptides. The PD index is a statistically validated method to detect discrete regions of proteins that have a high probability of cross-reacting with IgE from allergic patients. PMID:18950868

  6. Does prostate brachytherapy treat the seminal vesicles? A dose-volume histogram analysis of seminal vesicles in patients undergoing combined PD-103 prostate implantation and external beam irradiation

    International Nuclear Information System (INIS)

    Stock, Richard G.; Lo, Yeh-Chi; Gaildon, Mohamoud; Stone, Nelson N.

    1999-01-01

    Purpose: Combined brachytherapy of the prostate and external beam irradiation (EBRT) of the prostate and seminal vesicles (SV) is becoming a popular treatment for high-risk prostate cancer. Dose-volume histogram (DVH) analysis of the SV in patients undergoing this treatment was performed to determine the dose distribution to the SV and the adequacy of this treatment in patients with potential SV involvement. Methods and Materials: Twenty-five consecutive patients were treated with a Pd-103 implant of the prostate alone and 45 Gy of EBRT to the prostate and SV. Attempts were not made to implant the SV but seeds were routinely placed at the junction of the prostate and SV. All patients underwent CT-based post implant dosimetric analysis 1 month after implantation. As part of this analysis, DVH were generated for the prostate and total SV volume (SVT). In addition, the SV was divided into 6-mm-thick volumes identified as SV1, SV2, SV3, SV4, and SV5 starting from the junction of the prostate and SV and extending distally. DVH were also generated for these structures. Delivered dose was defined as the D90 (dose delivered to 90% of the organ on DVH). Results: The median volumes in cc of the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 34.33, 9.75, 2.7, 3.48, 2.92, 3.18, and 1.96 respectively. The SVT contained from 0-9 seeds (median 2). There was little dose delivered to the SVT and SV volumes from the implanted prostate. The median D90 values for the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 8615 cGy, 675 cGy, 3100 cGy, 1329 cGy, 553 cGy, 246 cGy, and 67 cGy, respectively. The dose delivered to the prostate covered small percentages of SV. The percents of SV volumes covered by the prostate D90 were 11, 35, 3.3, 0, 0, and 0 for SVT, SV1, SV2, SV3, SV4, and SV5, respectively. Conclusions: DVH analysis of the SV reveals that dose generated from an implanted prostate contributes little to the SV. Those patients at high risk for SV involvement may be under treated

  7. Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

    Science.gov (United States)

    Linedale, Richard; Schmidt, Campbell; King, Brigid T; Ganko, Annabelle G; Simpson, Fiona; Panizza, Benedict J; Leggatt, Graham R

    2017-01-01

    Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.

  8. Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Richard Linedale

    Full Text Available Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.

  9. Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

    Science.gov (United States)

    Baumgartner, Christine; Fan, Dongjie; Fang, Margaret C; Singer, Daniel E; Witt, Daniel M; Schmelzer, John R; Williams, Marc S; Gurwitz, Jerry H; Sung, Sue Hee; Go, Alan S

    2018-04-14

    Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes. The Cardiovascular Research Network WAVE (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision ( ICD-9 ), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person-years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28). Results were not materially changed after additional adjustment for patient-level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes. Diagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors

  10. A case of fulminant Type 1 diabetes following anti-PD1 immunotherapy in a genetically susceptible patient.

    Science.gov (United States)

    Araújo, Manuel; Ligeiro, Dário; Costa, Luís; Marques, Filipa; Trindade, Helder; Correia, José Manuel; Fonseca, Candida

    2017-06-01

    Programmed cell death-1 protein (PD-1) is an immune checkpoint that has gained popularity in the treatment of several advanced cancers. Inhibiting this checkpoint is known to enhance immune response, but is also known to diminish immune tolerance and to increase autoimmune toxicity. We discuss a case of rapid onset fulminant Type 1 diabetes induced by treatment with anti-programmed cell death-1 monoclonal antibody, nivolumab, in a patient with late-stage non-small-cell lung adenocarcinoma. The patient had no history of previous diabetes but did reveal a high-risk genotype for Type 1 diabetes development (DR3-DQ2; DR4-DQ8). This finding supports that acute Type 1 diabetes can be an important adverse effect of immunotherapies targeting T-cell activation regulation. Because of the severity of this adverse effect, physicians should be aware of it, and studies directed to the detection of new biomarkers for early risk stratification (e.g., HLA) should be sought.

  11. Adaptation of the Fresenius PD+ Cycler for a hearing-impaired patient.

    Science.gov (United States)

    Kushner, A

    2000-01-01

    Continuous cycling peritoneal dialysis (CCPD) uses a cycler to perform dialysis exchanges and requires the patient to respond to an audible alarm signifying an interruption in the therapy. Consequently, an unassisted hearing-impaired patient could not use the system. By converting the standard alarm to a vibrating signal, the cycler was successfully adapted to accommodate the special needs of our hearing-impaired patient. The items required for the modification were the Sonic Alert Wake Up Alarm (Model SA-WA300: Sonic Alert, Troy, MI, U.S.A.) and the Sonic Alert Super Shaker Bed Vibrator (Model SA-SS120V: Sonic Alert). The patient can place the vibrator under either the pillow or the mattress. When the cycler alarm is activated, vibration wakens the patient. The equipment was purchased from Harris Communications (Eden Prairie, MN, U.S.A.) through a referral by the Easter Seal Society. Three days were needed to complete training compared to an average of one or two days for patients previously trained for continuous ambulatory peritoneal dialysis (CAPD). The patient remained on cycler therapy for approximately four months when the unrelated development of an abdominal hernia required termination of peritoneal dialysis and subsequent transfer to hemodialysis. In conclusion, a modified cycler can provide a safe and efficient renal replacement therapy option for a hearing-impaired patient.

  12. PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation

    International Nuclear Information System (INIS)

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-01-01

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1 hi TIM-3 + cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1 hi TIM-3 + T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing T N and T EMRA subsets. Importantly, increase of PD-1 hi TIM-3 + cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation

  13. Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study

    Science.gov (United States)

    Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J.; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh F.; Egger, Matthias; Boulle, Andrew; Myer, Landon

    2012-01-01

    Background Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART. Methods and Findings Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing

  14. Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study.

    Directory of Open Access Journals (Sweden)

    Morna Cornell

    Full Text Available Increased mortality among men on antiretroviral therapy (ART has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA. Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF, virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years, during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001, were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001, and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001 and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22-1.41. After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12-1.28 but not to die after LTF (AHR 1.04, 95% CI 0.86-1.25. Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease

  15. Body Weight and Body Mass Index in Patients with End-Stage Cystic Fibrosis Stabilize After the Start of Enteral Tube Feeding.

    Science.gov (United States)

    Hollander, Francis M; de Roos, Nicole M; Belle van Meerkerk, Gerdien; Teding van Berkhout, Ferdinand; Heijerman, Harry G M; van de Graaf, Ed A

    2017-11-01

    Enteral tube feeding (ETF) is widely used in patients with cystic fibrosis (CF) and end-stage lung disease, but previous studies have been limited to investigating whether ETF improves outcomes in patients with moderately or mildly impaired pulmonary function. This study investigated body weight, body mass index (BMI; calculated as kg/m 2 ), pulmonary function, and the presence of CF-related diabetes before and after the start of ETF. This was a retrospective observational study. Data from 26 adult patients in an outpatient setting who had end-stage CF (19 women) and had been using ETF for at least 6 months between 2000 and 2014 were analyzed. Body weight, BMI, pulmonary function (forced expiratory volume in 1 second as percent of predicted) and incidence of CF-related diabetes from 6 months before to 6 months after starting ETF. Time effects were tested with one-way analysis of variance for data that were normally distributed and the Friedman test for non-parametric data. Correlations were tested with Pearson's r or Spearman's ρ, depending on the distribution of the data. Mean body weight increased by 3.5 kg (95% CI 2.2 to 4.8 kg) after patients started ETF. In women, mean BMI decreased by 0.7 in the 6 months before the start of ETF (PETF to 25% after 6 months (P=0.0013), with similar trends in women and men. There was no correlation between changes in weight and lung function. CF-related diabetes was already present in 12 patients and developed in 1 more patient after the start of ETF. ETF improved body weight and BMI but not pulmonary function in 26 patients with end-stage CF. Clinical outcomes were similar in women and men, but the sample size of men was too small to determine statistical significance. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  16. A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model of the histone deacetylase (HDAC) inhibitor vorinostat for pediatric and adult patients and its application for dose specification.

    Science.gov (United States)

    Moj, Daniel; Britz, Hannah; Burhenne, Jürgen; Stewart, Clinton F; Egerer, Gerlinde; Haefeli, Walter E; Lehr, Thorsten

    2017-11-01

    This study aimed at recommending pediatric dosages of the histone deacetylase (HDAC) inhibitor vorinostat and potentially more effective adult dosing regimens than the approved standard dosing regimen of 400 mg/day, using a comprehensive physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling approach. A PBPK/PD model for vorinostat was developed for predictions in adults and children. It includes the maturation of relevant metabolizing enzymes. The PBPK model was expanded by (1) effect compartments to describe vorinostat concentration-time profiles in peripheral blood mononuclear cells (PBMCs), (2) an indirect response model to predict the HDAC inhibition, and (3) a thrombocyte model to predict the dose-limiting thrombocytopenia. Parameterization of drug and system-specific processes was based on published and unpublished in silico, in vivo, and in vitro data. The PBPK modeling software used was PK-Sim and MoBi. The PBPK/PD model suggests dosages of 80 and 230 mg/m 2 for children of 0-1 and 1-17 years of age, respectively. In comparison with the approved standard treatment, in silico trials reveal 11 dosing regimens (9 oral, and 2 intravenous infusion rates) increasing the HDAC inhibition by an average of 31%, prolonging the HDAC inhibition by 181%, while only decreasing the circulating thrombocytes to a tolerable 53%. The most promising dosing regimen prolongs the HDAC inhibition by 509%. Thoroughly developed PBPK models enable dosage recommendations in pediatric patients and integrated PBPK/PD models, considering PD biomarkers (e.g., HDAC activity and platelet count), are well suited to guide future efficacy trials by identifying dosing regimens potentially superior to standard dosing regimens.

  17. Sequential SPECT/CT imaging starting with stress SPECT in patients with left bundle branch block suspected for coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Engbers, Elsemiek M.; Mouden, Mohamed [Isala, Department of Cardiology, Zwolle (Netherlands); Isala, Department of Nuclear Medicine, Zwolle (Netherlands); Timmer, Jorik R.; Ottervanger, Jan Paul [Isala, Department of Cardiology, Zwolle (Netherlands); Knollema, Siert; Jager, Pieter L. [Isala, Department of Nuclear Medicine, Zwolle (Netherlands)

    2017-01-15

    To investigate the impact of left bundle branch block (LBBB) on sequential single photon emission computed tomography (SPECT)/ CT imaging starting with stress-first SPECT. Consecutive symptomatic low- to intermediate-risk patients without a history of coronary artery disease (CAD) referred for SPECT/CT were included from an observational registry. If stress SPECT was abnormal, additional rest SPECT and, if feasible, coronary CT angiography (CCTA) were acquired. Of the 5,018 patients, 218 (4.3 %) demonstrated LBBB. Patients with LBBB were slightly older than patients without LBBB (65±12 vs. 61±11 years, p<0.001). Stress SPECT was more frequently abnormal in patients with LBBB (82 % vs. 46 %, p<0.001). After reviewing stress and rest images, SPECT was normal in 43 % of the patients with LBBB, compared to 77 % of the patients without LBBB (p<0.001). Sixty-four of the 124 patients with LBBB and abnormal stress-rest SPECT underwent CCTA (52 %), which could exclude obstructive CAD in 46 of the patients (72 %). Sequential SPECT/CT imaging starting with stress SPECT is not the optimal imaging protocol in patients with LBBB, as the majority of these patients have potentially false-positive stress SPECT. First-line testing using CCTA may be more appropriate in low- to intermediate-risk patients with LBBB. (orig.)

  18. CD3+/CD8+ T-cell density and tumoral PD-L1 predict survival irrespective of rituximab treatment in Chinese diffuse large B-cell lymphoma patients.

    Science.gov (United States)

    Shi, Yunfei; Deng, Lijuan; Song, Yuqin; Lin, Dongmei; Lai, Yumei; Zhou, LiXin; Yang, Lei; Li, Xianghong

    2018-05-10

    To investigate the prognostic value of tumor-infiltrating T-cell density and programmed cell death ligand-1 (PD-L1) expression in diffuse large B cell lymphoma (DLBCL). One-hundred-twenty-five Chinese DLBCL patients were enrolled in our study and provided samples; 76 of all cases were treated with rituximab (R). Tumor tissues were immunostained and analyzed for CD3+ and CD8+ tumor-infiltrating T-cell density, tumoral PD-L1, and microenvironmental PD-L1 (mPD-L1). The density of CD3 was rated as high in 33.6% cases, while 64.0% of DLBCLs were classified as high CD8 density. Of all cases, 16.8% were PD-L1+. Of the remaining PD-L1-DLBCLs, 29.8% positively expressed mPD-L1. Both CD3 high density and CD8 high density were associated with mPD-L1 positivity (P = 0.001 and P = 0.0001). In multivariate analysis, independently, high CD3 density predicted better OS (P = 0.023), while CD8 high density and PD-L1 positivity were both associated with prolonged PFS (P = 0.013 and P = 0.036, respectively). Even in the subgroup treated with R, univariate analyses indicated that high CD3 density and PD-L1 positivity were associated with better OS (P = 0.041) and PFS (P = 0.033), respectively. The infiltrating densities of CD3+ T-cells, CD8+ T-cells, and PD-L1 expression are predictive of survival in DLBCLs, irrespective of R usage.

  19. Usability and utility evaluation of the web-based "Should I Start Insulin?" patient decision aid for patients with type 2 diabetes among older people.

    Science.gov (United States)

    Lee, Yew Kong; Lee, Ping Yein; Ng, Chirk Jenn; Teo, Chin Hai; Abu Bakar, Ahmad Ihsan; Abdullah, Khatijah Lim; Khoo, Ee Ming; Hanafi, Nik Sherina; Low, Wah Yun; Chiew, Thiam Kian

    2018-01-01

    This study aimed to evaluate the usability (ease of use) and utility (impact on user's decision-making process) of a web-based patient decision aid (PDA) among older-age users. A pragmatic, qualitative research design was used. We recruited patients with type 2 diabetes who were at the point of making a decision about starting insulin from a tertiary teaching hospital in Malaysia in 2014. Computer screen recording software was used to record the website browsing session and in-depth interviews were conducted while playing back the website recording. The interviews were analyzed using the framework approach to identify usability and utility issues. Three cycles of iteration were conducted until no more major issues emerged. Thirteen patients participated: median age 65 years old, 10 men, and nine had secondary education/diploma, four were graduates/had postgraduate degree. Four usability issues were identified (navigation between pages and sections, a layout with open display, simple language, and equipment preferences). For utility, participants commented that the website influenced their decision about insulin in three ways: it had provided information about insulin, it helped them deliberate choices using the option-attribute matrix, and it allowed them to involve others in their decision making by sharing the PDA summary printout.

  20. Common mutations in G6PD of Vietnamese-Kinh deficient patients

    African Journals Online (AJOL)

    DANG THI LAN ANH

    2013-03-20

    Mar 20, 2013 ... (2009) found out six mutations in Kinh and Stieng's ethnics population by ... 6. P. D e n z y m e a c tiv ity. (IU. /g. Hb. ) Figure 1. Distribution of patients within the enzyme activity level. step lysis method. This method was improved from method of. Chaimosit ... sent to Sigma Aldrich- Singapore for synthesis.

  1. Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study

    Directory of Open Access Journals (Sweden)

    Sijpkens Yvo WJ

    2011-08-01

    Full Text Available Abstract Background To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD, we studied the association of systolic (SBP and diastolic blood pressure (DBP with decline in renal function and time until the start of renal replacement therapy (RRT in patients with CKD stages IV-V on pre-dialysis care. Methods In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1st 2008. Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT. Results A total of 508 patients, 57% men and median (IQR age of 63 (50-73 years, were available for analyses. Mean (SD decline in renal function was 0.35 (0.75 ml/min/1.73 m2/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07 and 0.05 (0.00;0.11 ml/min/1.73 m2/month respectively and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14 and 1.16 (1.05;1.28 respectively. Furthermore, patients with SBP and DBP above the BP target goal of 2/month and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44, compared to patients who achieved the target goal (11%. Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg and patients with both SBP and DBP below the target (2/month and adjusted HR 2.24 (1.26;3.97. Therefore, it seems that especially having SBP above the target is harmful. Conclusions In pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP above the target goal for CKD patients (

  2. Quality of life in patients on chronic dialysis: self-assessment 3 months after the start of treatment. The Necosad Study Group

    NARCIS (Netherlands)

    Merkus, M. P.; Jager, K. J.; Dekker, F. W.; Boeschoten, E. W.; Stevens, P.; Krediet, R. T.

    1997-01-01

    The aim of the present multicenter study was to assess quality of life of Dutch dialysis patients 3 months after the start of chronic dialysis treatment. The quality of life was compared with the quality of life of a general population sample, and the impact of demographic, clinical, renal function,

  3. Feasibility of the STarT back screening tool in chiropractic clinics: a cross-sectional study of patients with low back pain

    DEFF Research Database (Denmark)

    Kongsted, Alice; Johannesen, Else; Leboeuf-Yde, Charlotte

    2011-01-01

    The STarT back screening tool (SBT) allocates low back pain (LBP) patients into three risk groups and is intended to assist clinicians in their decisions about choice of treatment. The tool consists of domains from larger questionnaires that previously have been shown to be predictive of non-reco...

  4. Fusion of 110Pd with 110Pd

    International Nuclear Information System (INIS)

    Morawek, W.

    1991-07-01

    In the framework of this thesis the excitation functions of the systems 110 Pd + 110 Pd and 110 Pd + 104 Ru could be measured. The evaporation-residual-nucleus cross sections is deviating from lighter systems dominated by channels, which arise from evaporation of α particles. In the reaction 110 Pd + 110 Pd no xn channels were observed. In comparison to other reactions qualitatively a strong fusion hindrance of this system is shown. (orig./HSI) [de

  5. Implant R100 Predicts Rectal Bleeding in Prostate Cancer Patients Treated with IG-IMRT to 45 Gy and Pd-103 Implant

    International Nuclear Information System (INIS)

    Packard, M.; Fuhrer, R.; Valakh, V.

    2014-01-01

    Purpose. To define factors associated with rectal bleeding in patients treated with IG-IMRT followed by Pd-103 seed implant. Methods and Materials. We retrospectively reviewed 61 prostate adenocarcinoma patients from 2002 to 2008. The majority (85.2%) were of NCCN intermediate risk category. All received IG-IMRT to the prostate and seminal vesicles followed by Pd-103 implant delivering a mean D90 of 100.7 Gy. Six patients received 45 Gy to the pelvic nodes and 10 received androgen deprivation. Results. Ten patients (16.4%) developed rectal bleeding: 4 were CTCAE v.3 grade 1, 5 were grade 2, and 1 was grade 3. By univariate analysis, age, stage, Gleason sum, PSA, hormonal therapy, pelvic radiation, postoperative prostate volume, D9, V100, individual source activity, total implanted activity per cm 3 , and duration of interval before implant did not impact rectal bleeding. Implant R100 was higher in patients with rectal bleeding: on average, 0.885 versus 0.396 cm 3 ,(Ρ =0.02) , odds ratio of 2.26 per .5 cm 3 (95% CI, 1.16–4.82). A trend for significance was seen for prostate V200 and total implanted activity. Conclusion. Higher implant R100 was associated with development of rectal bleeding in patients receiving IG-IMRT to 45 Gy followed by Pd-103 implant. Minimizing implant R100 may reduce the rate of rectal bleeding in similar patients.

  6. PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy

    Directory of Open Access Journals (Sweden)

    Junyu Long

    2017-08-01

    Full Text Available Abstract Gastrointestinal (GI malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.

  7. PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy.

    Science.gov (United States)

    Long, Junyu; Lin, Jianzhen; Wang, Anqiang; Wu, Liangcai; Zheng, Yongchang; Yang, Xiaobo; Wan, Xueshuai; Xu, Haifeng; Chen, Shuguang; Zhao, Haitao

    2017-08-03

    Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.

  8. Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients

    Science.gov (United States)

    Napolitano, Maria; D'Alterio, Crescenzo; Cardone, Eleonora; Trotta, Anna Maria; Pecori, Biagio; Rega, Daniela; Pace, Ugo; Scala, Dario; Scognamiglio, Giosuè; Tatangelo, Fabiana; Cacciapuoti, Carmela; Pacelli, Roberto; Delrio, Paolo; Scala, Stefania

    2015-01-01

    Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN−/HLA-DR−/CD11b+/CD14−/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR−/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD). Peripheral MDSC and Tregs were evaluated at time 0 (T0), after 2 and 5 weeks (T2-T5) from radiotherapy; before surgery (T8) and 6–12 months after surgery (T9, T10). G-MDSC decreased at T5 and further at T8 while M-MDSC cells decreased at T5; Tregs reached the lowest value at T5. LARC poor responder patients displayed a major decrease in M-MDSC after SC-RT and an increase of Treg-PD-1. In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients. Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5–8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT. PMID:25823653

  9. Characterization of patients diagnosed with central precocious puberty starting treatment with leuprolide acetate, at the Hospital Nacional de Ninos in the period January 2004 to December 2009

    International Nuclear Information System (INIS)

    Viquez Viquez, Natalia

    2013-01-01

    Clinical characteristics and laboratory and cabinet findings (hormone levels, bone age, pelvic ultrasound) were determined in a sample of 39 patients diagnosed with central precocious puberty (CPP) who started treatment with leuprolide acetate (LPA). The cross-sectional observational study was developed at the Hospital Nacional de Ninos 'Dr. Carlos Saenz Herrera' during the period 2004 and 2009. The chronological age of patients with CPP was specified at the time of diagnosis and to start treatment with LPA. Epidemiological characteristics (sex, origin) were described in patients with CPP. Bone age with respect to chronological age was identified in patients with CPP. Sexual maturity of patients with CPP was established by the Tanner scale. The hormone levels of estrogen, testosterone, luteinizing hormone and follicle stimulating hormone were specified in patients with CPP. The etiology was determined in patients with CPP treated with LPA. The adverse effects of treatment with LPA were described. Anthropometric measurements were detailed. The heredo-familial antecedents of precocious puberty were established in patients with diagnosis of CPP. The size of the pelvic organs was evaluated by pelvic ultrasound [es

  10. Impact of a Two-step Emergency Department Triage Model with START, then CTAS, on Patient Flow During a Simulated Mass-casualty Incident.

    Science.gov (United States)

    Lee, James S; Franc, Jeffrey M

    2015-08-01

    A high influx of patients during a mass-casualty incident (MCI) may disrupt patient flow in an already overcrowded emergency department (ED) that is functioning beyond its operating capacity. This pilot study examined the impact of a two-step ED triage model using Simple Triage and Rapid Treatment (START) for pre-triage, followed by triage with the Canadian Triage and Acuity Scale (CTAS), on patient flow during a MCI simulation exercise. Hypothesis/Problem It was hypothesized that there would be no difference in time intervals nor patient volumes at each patient-flow milestone. Physicians and nurses participated in a computer-based tabletop disaster simulation exercise. Physicians were randomized into the intervention group using START, then CTAS, or the control group using START alone. Patient-flow milestones including time intervals and patient volumes from ED arrival to triage, ED arrival to bed assignment, ED arrival to physician assessment, and ED arrival to disposition decision were compared. Triage accuracy was compared for secondary purposes. There were no significant differences in the time interval from ED arrival to triage (mean difference 108 seconds; 95% CI, -353 to 596 seconds; P=1.0), ED arrival to bed assignment (mean difference 362 seconds; 95% CI, -1,269 to 545 seconds; P=1.0), ED arrival to physician assessment (mean difference 31 seconds; 95% CI, -1,104 to 348 seconds; P=0.92), and ED arrival to disposition decision (mean difference 175 seconds; 95% CI, -1,650 to 1,300 seconds; P=1.0) between the two groups. There were no significant differences in the volume of patients to be triaged (32% vs 34%; 95% CI for the difference -16% to 21%; P=1.0), assigned a bed (16% vs 21%; 95% CI for the difference -11% to 20%; P=1.0), assessed by a physician (20% vs 22%; 95% CI for the difference -14% to 19%; P=1.0), and with a disposition decision (20% vs 9%; 95% CI for the difference -25% to 4%; P=.34) between the two groups. The accuracy of triage was similar

  11. Predictors of work disability after start of anti-TNF therapy in a national cohort of Swedish patients with rheumatoid arthritis: does early anti-TNF therapy bring patients back to work?

    Science.gov (United States)

    Olofsson, T; Petersson, I F; Eriksson, J K; Englund, M; Nilsson, J A; Geborek, P; Jacobsson, L T H; Askling, J; Neovius, M

    2017-07-01

    To examine predictors of work ability gain and loss after anti-tumour necrosis factor (TNF) start, respectively, in working-age patients with rheumatoid arthritis (RA) with a special focus on disease duration. Patients with RA, aged 19-62 years, starting their first TNF inhibitor 2006-2009 with full work ability (0 sick leave/disability pension days during 3 months before bio-start; n=1048) or no work ability (90 days; n=753) were identified in the Swedish biologics register (Anti-Rheumatic Treatment In Sweden, ARTIS) and sick leave/disability pension days retrieved from the Social Insurance Agency. Outcome was defined as work ability gain ≥50% for patients without work ability at bio-start and work ability loss ≥50% for patients with full work ability, and survival analyses conducted. Baseline predictors including disease duration, age, sex, education level, employment, Health Assessment Questionnaire, Disease Activity Score 28 and relevant comorbidities were estimated using Cox regression. During 3 years after anti-TNF start, the probability of regaining work ability for totally work-disabled patients was 35% for those with disease duration start, disease duration did not predict work ability loss. Baseline disability pension was also a strong predictor of work ability gain after treatment start. A substantial proportion of work-disabled patients with RA who start anti-TNF therapy regain work ability. Those initiating treatment within 5 years of symptom onset have a more than doubled 3-year probability of regaining work ability compared with later treatment starts. This effect seems largely due to the impact of disease duration on disability pension status. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. UK Renal Registry 18th Annual Report: Chapter 11 2014 Multisite Dialysis Access Audit in England, Northern Ireland and Wales and 2013 PD One Year Follow-up: National and Centre-specific Analyses.

    Science.gov (United States)

    Rao, Anirudh; Evans, Rebecca; Wilkie, Martin; Fluck, Richard; Kumwenda, Mick

    2016-01-01

    Data are presented from the third combined vascular and peritoneal dialysis access audit. In 2014, 53 centres in England, Wales and Northern Ireland (out of 62) returned data on first access from 4,339 incident haemodialysis (HD) patients and 1,090 incident peritoneal dialysis (PD) patients. Of the 5,429 incident patients, 20.1% started dialysis on PD, 27.8% started with an arteriovenous fistula (AVF), 1.0% with an arteriovenous graft (AVG), 27.1% on a tunnelled line (TL) and 24.0% on a non-tunnelled line (NTL). Older patients (565 years) were more likely to start haemodialysis using AVF compared to their younger counterparts (36.2% vs. 32.8%). Thirteen of the nineteen centres (68%) using the physician led percutaneous insertion technique had over 20% of their incident patients starting on PD when compared to only seven out of fourteen centres (50%) which used single technique (open surgical or laparoscopic) for their PD catheter insertion. Wide variations were apparent between centres for use of AVF as the first haemodialysis access ranging from 10–54%. Eight of the 49 centres were achieving close to the 65% target for AV fistula in their incident patients. Length of time known to nephrology services and likelihood of commencing dialysis using either an AVF or a PD catheter are strongly associated. Patients who were known to a nephrologist for over one year were more likely to start dialysis with AVF, as compared to those who were referred between 90–365 days (39.2% vs. 24.6%). Similarly, patients who were known to a nephrologist between 90 days and one year were more likely to start on PD when compared to patients who were referred report demonstrates wide variations in practice between centres across several domains in the provision of dialysis access and further work will be required to understand the underlying reasons.

  13. Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.

    Science.gov (United States)

    Yamada, Rin; Yamaguchi, Tatsuro; Iijima, Takeru; Wakaume, Rika; Takao, Misato; Koizumi, Koichi; Hishima, Tsunekazu; Horiguchi, Shin-Ichiro

    2018-06-01

    The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55-37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50-45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

  14. Evaluating the significance of density, localization, and PD-1/PD-L1 immunopositivity of mononuclear cells in the clinical course of lung adenocarcinoma patients with brain metastasis

    DEFF Research Database (Denmark)

    Téglási, Vanda; Reiniger, Lilla; Fabian, Katalin

    2017-01-01

    Background. Management of lung cancer patients who suffer from brain metastases represents a major challenge. Considering the promising results with immune checkpoint inhibitor treatment, evaluating the status of immune cell (IC) infiltrates in the prognosis of brain metastasis may lead to better...

  15. Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD-1, TIGIT, and TIM-3 in Lymphocytes From Patients With Systemic Sclerosis.

    Science.gov (United States)

    Fleury, Michelle; Belkina, Anna C; Proctor, Elizabeth A; Zammitti, Christopher; Simms, Robert W; Lauffenburger, Douglas A; Snyder-Cappione, Jennifer E; Lafyatis, Robert; Dooms, Hans

    2018-04-01

    Immune dysfunction is an important component of the disease process underlying systemic sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. This study was undertaken to measure the expression and function of the coinhibitory receptors (co-IRs) programmed cell death 1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in lymphocyte subsets from the peripheral blood of patients with SSc. Co-IR expression levels on subsets of immune cells were analyzed using a 16-color flow cytometry panel. The functional role of co-IRs was determined by measuring cytokine production after in vitro stimulation of SSc and healthy control peripheral blood mononuclear cells (PBMCs) in the presence of co-IR-blocking antibodies. Supernatants from cultures of stimulated PBMCs were added to SSc fibroblasts, and their impact on fibroblast gene expression was measured. Mathematical modeling was used to reveal differences between co-IR functions in SSc patients and healthy controls. Levels of the co-IRs PD-1 and TIGIT were increased, and each was coexpressed, in distinct T cell subsets from SSc patients compared to healthy controls. Levels of TIM-3 were increased in SSc natural killer cells. PD-1, TIGIT, and TIM-3 antibody blockade revealed patient-specific roles of each of these co-IRs in modulating activation-induced T cell cytokine production. In contrast to healthy subjects, blockade of TIGIT and TIM-3, but not PD-1, failed to reverse inhibited cytokine production in SSc patients, indicating that enhanced T cell exhaustion is present in SSc. Finally, cytokines secreted in anti-TIM-3-treated PBMC cultures distinctly changed the gene expression profile in SSc fibroblasts. The altered expression and regulatory capacity of co-IRs in SSc lymphocytes may contribute to disease pathophysiology by modulating the cytokine-mediated cross-talk of

  16. Evaluation of a pharmacy service helping patients to get a good start in taking their new medications for chronic diseases

    DEFF Research Database (Denmark)

    Kaae, Susanne; Dam, Pernille; Rossing, Charlotte

    2016-01-01

    . Further, semi-structured interviews were carried out with a subset of patients to explore their experiences in more depth. Questionnaires were analyzed using IBM SPSS Statistics 19, and interviews were analyzed using meaning condensation. RESULTS: Patients reported improved knowledge, feelings of safety...

  17. De-isolation of patients with pulmonary tuberculosis after start of treatment - clear, unequivocal guidelines are missing

    DEFF Research Database (Denmark)

    Petersen, Eskild; Khamis, Faryal; Migliori, Giovanni Battista

    2017-01-01

    The study review guidelines on isolation of patients with tuberculosis, TB, from the World Health Organization, WHO, Centers for Disease Control and Prevention, CDC, and the European Center for Disease Control, ECDC. The review found that unequivocal guidelines for removing patients out of negative...

  18. Using mHealth for HIV/TB Treatment Support in Lesotho: Enhancing Patient-Provider Communication in the START Study.

    Science.gov (United States)

    Hirsch-Moverman, Yael; Daftary, Amrita; Yuengling, Katharine A; Saito, Suzue; Ntoane, Moeketsi; Frederix, Koen; Maama, Llang B; Howard, Andrea A

    2017-01-01

    mHealth is a promising means of supporting adherence to treatment. The Start TB patients on ART and Retain on Treatment (START) study included real-time adherence support using short-text messaging service (SMS) text messaging and trained village health workers (VHWs). We describe the use and acceptability of mHealth by patients with HIV/tuberculosis and health care providers. Patients and treatment supporters received automated, coded medication and appointment reminders at their preferred time and frequency, using their own phones, and $3.70 in monthly airtime. Facility-based VHWs were trained to log patient information and text message preferences into a mobile application and were given a password-protected mobile phone and airtime to communicate with community-based VHWs. The use of mHealth tools was analyzed from process data over the study course. Acceptability was evaluated during monthly follow-up interviews with all participants and during qualitative interviews with a subset of 30 patients and 30 health care providers at intervention sites. Use and acceptability were contextualized by monthly adherence data. From April 2013 to August 2015, the automated SMS system successfully delivered 39,528 messages to 835 individuals, including 633 patients and 202 treatment supporters. Uptake of the SMS intervention was high, with 92.1% of 713 eligible patients choosing to receive SMS messages. Patient and provider interviews yielded insight into barriers and facilitators to mHealth utilization. The intervention improved the quality of health communication between patients, treatment supporters, and providers. HIV-related stigma and technical challenges were identified as potential barriers. The mHealth intervention for HIV/tuberculosis treatment support in Lesotho was found to be a low-tech, user-friendly intervention, which was acceptable to patients and health care providers.

  19. Diurnal fluctuation of leukocyte G6PD activity. A possible explanation for the normal neutrophil bactericidal activity and the low incidence of pyogenic infections in patients with severe G6PD deficiency in Israel

    NARCIS (Netherlands)

    Wolach, Baruch; Ashkenazi, Meir; Grossmann, Rami; Gavrieli, Ronit; Friedman, Ziva; Bashan, Nava; Roos, Dirk

    2004-01-01

    Acute hemolytic anemia associated with red blood cell (RBC) glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly encountered in the Mediterranean basin. Nevertheless, concomitant clinical evidence of white blood cell G6PD deficiency is extremely rare in Israel. This study sought to assess

  20. Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy

    Directory of Open Access Journals (Sweden)

    Xiubao Ren

    2017-04-01

    Full Text Available Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4 plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1 in non-small cell lung cancer (NSCLC tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled. All the patients had integrated clinicopathological records and follow-up data. TLR4 and PD-L1 expression on NSCLC samples were determined by immunohistochemistry, and serum soluble TLR4 (sTLR4 levels were measured by enzyme-linked immunosorbent assay. Results showed that TLR4 expression level in cancer tissue was significantly higher than that in para-cancer tissue. Elevated TLR4 expression was significantly associated with histological type (adenocarcinoma higher than squamous cell carcinoma, P = 0.041, increased clinical TNM stage (P < 0.001, and presence of lymphatic invasion (P < 0.001. Besides, TLR4 expression level in cancer samples was inversely correlated with serum sTLR4 level in patients with early-stage NSCLC (r = −0.485, P = 0.003. TLR4 expression level was also positively correlated with the PD-L1 expression level (r = 0.545, P < 0.0001. Multivariate analysis showed that expression level of TLR4 was an independent prognostic factor and TLR4 overexpression indicated a poor overall survival and disease-free survival. Taken together, we conclude that expression of TLR4 in lung cancer is associated with PD-L1 and could predict the outcome of patients with NSCLC receiving pulmonary resection for cancer.

  1. Packed red blood cell transfusion causes greater hemoglobin rise at a lower starting hemoglobin in patients with subarachnoid hemorrhage.

    Science.gov (United States)

    Naidech, Andrew M; Kahn, Marc J; Soong, Wayne; Green, David; Batjer, H Hunt; Bleck, Thomas P

    2008-01-01

    Each unit of packed red blood cells (PRBCs) is expected to raise circulating hemoglobin (HGB) by approximately 1 g/dL. There are few data on modifiers of this relationship other than gender and body mass index (BMI). We recorded HGB before and after PRBC transfusion in a retrospective cohort of 103 patients and a prospective cohort of 93 patients with subarachnoid hemorrhage (SAH). In the retrospective cohort, 48 of 103 patients were transfused, and in the prospective cohort, 56 of 93 patients were transfused. In both groups, lower pre-transfusion HGB was associated with a larger increase in HGB (P rise in HGB (P < 0.001) after correction for number of units of PRBCs given, gender, and BMI in repeated measures analysis. Pre-transfusion HGB explained an additional 12% of variance in the data (P < 0.001). In both cohorts, the magnitude of the effect was similar. In patients with SAH, transfusion at lower HGB leads to a greater increase in HGB. Transfusion at lower HGB may be relatively more cost-effective, and this should be balanced against any potential benefit from higher HGB in SAH. One rather than 2 units of PRBCs are likely to be sufficient for most HGB targets after SAH, especially in patients with more severe anemia.

  2. Acute hypophosphataemia and hypokalaemia in a patient starting antiretroviral therapy in Zambia—a new context for refeeding syndrome?

    Science.gov (United States)

    Nyirenda, Christopher; Zulu, Isaac; Kabagambe, Edmond K; Bagchi, Shashwatee; Potter, Dara; Bosire, Claire; Krishnasami, Zipporah; Heimburger, Douglas C

    2009-01-01

    High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries. PMID:21686792

  3. Validation of the Risk Prediction Models STATE-Score and START-Strategy to Guide TACE Treatment in Patients with Hepatocellular Carcinoma.

    Science.gov (United States)

    Mähringer-Kunz, Aline; Kloeckner, Roman; Pitton, Michael B; Düber, Christoph; Schmidtmann, Irene; Galle, Peter R; Koch, Sandra; Weinmann, Arndt

    2017-07-01

    Several scoring systems that guide patients' treatment regimen for transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) have been introduced, but none have gained widespread acceptance in clinical practice. The purpose of this study is to externally validate the Selection for TrAnsarterial chemoembolization TrEatment (STATE)-score and START-strategy [i.e., sequential use of the STATE-score and Assessment for Retreatment with TACE (ART)-score]. From January 2000 to September 2015, 933 patients with HCC underwent TACE at our institution. All variables needed to calculate the STATE-score and implement the START-strategy were determined. STATE comprised serum albumin, up-to-seven criteria, and C-reactive protein (CRP). ART comprised an increase in aspartate aminotransferase, the Child-Pugh score, and a radiological tumor response. Overall survival was calculated, and multivariate analysis performed. In addition, the STATE-score and START-strategy were validated using the Harrell's C-index and integrated Brier score (IBS). The STATE-score was calculated in 228 patients. Low and high STATE-scores corresponded to median survival of 14.3 and 20.2 months, respectively. Harrell's C was 0.558 and IBS 0.133. For the STATE-score, significant predictors of survival were up-to-seven criteria (p = 0.006) and albumin (p = 0.022). CRP values were not predictive (p = 0.367). The ART-score was calculated in 207 patients. Combining the STATE-score and ART-score led to a Harrell's C of 0.580 and IBS of 0.132. The STATE-score was unable to reliably determine the suitability for initial TACE. The START-strategy only slightly improved the predictive ability compared to the ART-score alone. Therefore, neither the STATE-score nor START-strategy alone provides sufficient certainty for clear-cut clinical decisions.

  4. Exploring a new ultrasound score as a clinical predictive tool in patients with rheumatoid arthritis starting abatacept

    DEFF Research Database (Denmark)

    D'Agostino, Maria-Antonietta; Boers, Maarten; Wakefield, Richard J

    2016-01-01

    Objectives: To explore whether changes in a composite ( power Doppler/greyscale ultrasound (PDUS)) synovitis score, developed by the OMERACT-EULAR-Ultrasound Task Force, predict disease activity outcomes in rheumatoid arthritis (RA). Methods: Patients with RA who were methotrexate inadequate...

  5. Health education to diabetic patients before the start of Ramadan: Experience from a teaching hospital in Dammam

    Directory of Open Access Journals (Sweden)

    Rayyan M Al-Musally

    2017-01-01

    CONCLUSION: The adherence to the pre-Ramadan educational program by the treating physician was low. It is necessary to increase the awareness about the importance of these programs among health-care professionals. The programs should target the less educated, the unemployed, and older patients.

  6. Estimation of the dose to patients in conventional radiology to starting from the data obtained in the quality controls

    International Nuclear Information System (INIS)

    Parra Osorio, V.; Casado Villalon, F. J.; Ortega Cantos, E.; Navarro Guirado, F.; Moreno Saiz, C.; Martin-Viera Cueto, J. A.

    2013-01-01

    The objective of this study is to estimate the dose on the surface of the entry of the patient on simple scans with x-rays from the information collected by the unit of Radiophysics in quality controls of equipment.To this end, we have selected three scans collected in this legislation: PA chest and Abdomen AP skull AP. (Author)

  7. The Association Between the STOPP/START Criteria and Gastro-Intestinal Track Bleedings in Elderly Patients

    NARCIS (Netherlands)

    Veldhuis, Anouk; Sent, Danielle; Bruin-Huisman, Linette; Beers, Erna; Abu-Hanna, Ameen

    2017-01-01

    Potentially inappropriate prescribing is a common problem, especially in elderly care. To tackle this problem, Irish medical experts have developed a list of criteria when medication should be added or omitted based upon the patient's physical condition and medication use, known as the STOPP and

  8. START (screening tool to alert doctors to the right treatment)--an evidence-based screening tool to detect prescribing omissions in elderly patients.

    LENUS (Irish Health Repository)

    Barry, P J

    2012-02-03

    BACKGROUND: Inappropriate prescribing encompasses acts of commission i.e. giving drugs that are contraindicated or unsuitable, and acts of omission i.e. failure to prescribe drugs when indicated due to ignorance of evidence base or other irrational basis e.g. ageism. There are considerable published data on the prevalence of inappropriate prescribing; however, there are no recent published data on the prevalence of acts of omission. The aim of this study was to calculate the prevalence of acts of prescribing omission in a population of consecutively hospitalised elderly people. METHODS: A screening tool (screening tool to alert doctors to the right treatment acronym, START), devised from evidence-based prescribing indicators and arranged according to physiological systems was prepared and validated for identifying prescribing omissions in older adults. Data on active medical problems and prescribed medicines were collected in 600 consecutive elderly patients admitted from the community with acute illness to a teaching hospital. On identification of an omitted medication, the patient\\'s medical records were studied to look for a valid reason for the prescribing omission. RESULTS: Using the START list, we found one or more prescribing omissions in 57.9% of patients. In order of prevalence, the most common prescribing omissions were: statins in atherosclerotic disease (26%), warfarin in chronic atrial fibrillation (9.5%), anti-platelet therapy in arterial disease (7.3%) and calcium\\/vitamin D supplementation in symptomatic osteoporosis (6%). CONCLUSION: Failure to prescribe appropriate medicines is a highly prevalent problem among older people presenting to hospital with acute illness. A validated screening tool (START) is one method of systematically identifying appropriate omitted medicines in clinical practice.

  9. Development and validation of the Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ) for primary care patients with type 2 diabetes.

    Science.gov (United States)

    Fu, Sau Nga; Chin, Weng Yee; Wong, Carlos King Ho; Yeung, Vincent Tok Fai; Yiu, Ming Pong; Tsui, Hoi Yee; Chan, Ka Hung

    2013-01-01

    To develop and evaluate the psychometric properties of a Chinese questionnaire which assesses the barriers and enablers to commencing insulin in primary care patients with poorly controlled Type 2 diabetes. Questionnaire items were identified using literature review. Content validation was performed and items were further refined using an expert panel. Following translation, back translation and cognitive debriefing, the translated Chinese questionnaire was piloted on target patients. Exploratory factor analysis and item-scale correlations were performed to test the construct validity of the subscales and items. Internal reliability was tested by Cronbach's alpha. Twenty-seven identified items underwent content validation, translation and cognitive debriefing. The translated questionnaire was piloted on 303 insulin naïve (never taken insulin) Type 2 diabetes patients recruited from 10 government-funded primary care clinics across Hong Kong. Sufficient variability in the dataset for factor analysis was confirmed by Bartlett's Test of Sphericity (P 0.4 and Eigenvalues >1. Total variance for the 10 factors was 66.22%. Kaiser-Meyer-Olkin measure was 0.725. Cronbach's alpha coefficients for the first four factors were ≥0.6 identifying four sub-scales to which 13 items correlated. Remaining sub-scales and items with poor internal reliability were deleted. The final 13-item instrument had a four scale structure addressing: 'Self-image and stigmatization'; 'Factors promoting self-efficacy; 'Fear of pain or needles'; and 'Time and family support'. The Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ) appears to be a reliable and valid measure for assessing barriers to starting insulin. This short instrument is easy to administer and may be used by healthcare providers and researchers as an assessment tool for Chinese diabetic primary care patients, including the elderly, who are unwilling to start insulin.

  10. Development and validation of the Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ for primary care patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Sau Nga Fu

    Full Text Available OBJECTIVES: To develop and evaluate the psychometric properties of a Chinese questionnaire which assesses the barriers and enablers to commencing insulin in primary care patients with poorly controlled Type 2 diabetes. RESEARCH DESIGN AND METHOD: Questionnaire items were identified using literature review. Content validation was performed and items were further refined using an expert panel. Following translation, back translation and cognitive debriefing, the translated Chinese questionnaire was piloted on target patients. Exploratory factor analysis and item-scale correlations were performed to test the construct validity of the subscales and items. Internal reliability was tested by Cronbach's alpha. RESULTS: Twenty-seven identified items underwent content validation, translation and cognitive debriefing. The translated questionnaire was piloted on 303 insulin naïve (never taken insulin Type 2 diabetes patients recruited from 10 government-funded primary care clinics across Hong Kong. Sufficient variability in the dataset for factor analysis was confirmed by Bartlett's Test of Sphericity (P 0.4 and Eigenvalues >1. Total variance for the 10 factors was 66.22%. Kaiser-Meyer-Olkin measure was 0.725. Cronbach's alpha coefficients for the first four factors were ≥0.6 identifying four sub-scales to which 13 items correlated. Remaining sub-scales and items with poor internal reliability were deleted. The final 13-item instrument had a four scale structure addressing: 'Self-image and stigmatization'; 'Factors promoting self-efficacy; 'Fear of pain or needles'; and 'Time and family support'. CONCLUSION: The Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ appears to be a reliable and valid measure for assessing barriers to starting insulin. This short instrument is easy to administer and may be used by healthcare providers and researchers as an assessment tool for Chinese diabetic primary care patients, including the elderly, who are

  11. Keele Aches and Pains Study protocol: validity, acceptability, and feasibility of the Keele STarT MSK tool for subgrouping musculoskeletal patients in primary care

    Directory of Open Access Journals (Sweden)

    Campbell P

    2016-10-01

    Full Text Available Paul Campbell,1 Jonathan C Hill,1 Joanne Protheroe,1 Ebenezer K Afolabi,1 Martyn Lewis,1 Ruth Beardmore,1 Elaine M Hay,1 Christian D Mallen,1 Bernadette Bartlam,1 Benjamin Saunders,1 Danielle A van der Windt,1 Sue Jowett,2 Nadine E Foster,1 Kate M Dunn1 1Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Keele, 2Health Economics Unit, University of Birmingham, Birmingham, UK Abstract: Musculoskeletal conditions represent a considerable burden worldwide, and are predominantly managed in primary care. Evidence suggests that many musculoskeletal conditions share similar prognostic factors. Systematically assessing patient’s prognosis and matching treatments based on prognostic subgroups (stratified care has been shown to be both clinically effective and cost-effective. This study (Keele Aches and Pains Study aims to refine and examine the validity of a brief questionnaire (Keele STarT MSK tool designed to enable risk stratification of primary care patients with the five most common musculoskeletal pain presentations. We also describe the subgroups of patients, and explore the acceptability and feasibility of using the tool and how the tool is best implemented in clinical practice. The study design is mixed methods: a prospective, quantitative observational cohort study with a linked qualitative focus group and interview study. Patients who have consulted their GP or health care practitioner about a relevant musculoskeletal condition will be recruited from general practice. Participating patients will complete a baseline questionnaire (shortly after consultation, plus questionnaires 2 and 6 months later. A subsample of patients, along with participating GPs and health care practitioners, will be invited to take part in qualitative focus groups and interviews. The Keele STarT MSK tool will be refined based on face, discriminant, construct, and predictive validity at baseline and 2

  12. The Safety and Immunogenicity of Live Zoster Vaccination in Patients With Rheumatoid Arthritis Before Starting Tofacitinib: A Randomized Phase II Trial.

    Science.gov (United States)

    Winthrop, Kevin L; Wouters, Ann G; Choy, Ernest H; Soma, Koshika; Hodge, Jennifer A; Nduaka, Chudy I; Biswas, Pinaki; Needle, Elie; Passador, Sherry; Mojcik, Christopher F; Rigby, William F

    2017-10-01

    Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster, and vaccination is recommended for patients ages 50 years and older, prior to starting treatment with biologic agents or tofacitinib. Tofacitinib is an oral JAK inhibitor for the treatment of RA. We evaluated its effect on the immune response and safety of live zoster vaccine (LZV). In this phase II, 14-week, placebo-controlled trial, patients ages 50 years and older who had active RA and were receiving background methotrexate were given LZV and randomized to receive tofacitinib 5 mg twice daily or placebo 2-3 weeks postvaccination. We measured humoral responses (varicella zoster virus [VZV]-specific IgG level as determined by glycoprotein enzyme-linked immunosorbent assay) and cell-mediated responses (VZV-specific T cell enumeration, as determined by enzyme-linked immunospot assay) at baseline and 2 weeks, 6 weeks, and 14 weeks postvaccination. End points included the geometric mean fold rise (GMFR) in VZV-specific IgG levels (primary end point) and T cells (number of spot-forming cells/10 6 peripheral blood mononuclear cells) at 6 weeks postvaccination. One hundred twelve patients were randomized to receive tofacitinib (n = 55) or placebo (n = 57). Six weeks postvaccination, the GMFR in VZV-specific IgG levels was 2.11 in the tofacitinib group and 1.74 in the placebo group, and the VZV-specific T cell GMFR was similar in the tofacitinib group and the placebo group (1.50 and 1.29, respectively). Serious adverse events occurred in 3 patients in the tofacitinib group (5.5%) and 0 patients (0.0%) in the placebo group. One patient, who lacked preexisting VZV immunity, developed cutaneous vaccine dissemination 2 days after starting tofacitinib (16 days postvaccination). This resolved after tofacitinib was discontinued and the patient received antiviral treatment. Patients who began treatment with tofacitinib 2-3 weeks after receiving LZV had VZV-specific humoral and cell

  13. Wegner′s granulomatosis developing for the first time in a patient eight years after starting maintenance hemodialysis

    Directory of Open Access Journals (Sweden)

    Ahmad Ramadan Ali

    2015-01-01

    Full Text Available Wegener′s granulomatosis is a serious autoimmune disorder characterized by necrotizing small-vessel vasculitis. It is a multisystem disease that primarily affects the lung and kidneys. Previous studies indicated few relapses of vasculitis after hemodialysis due to uremic immunosuppression. Our case report describes an end-stage renal failure patient who had developed non-caseating lung granulomata with giant cell formation and fibrinoid necrosis of arterial media that is consistent with Wegner′s granulomatosis for the first time and eight years after initiation of maintenance hemodialysis. We believe that such a phenomenon has rarely been reported.

  14. A guided self-help intervention targeting psychological distress among head and neck cancer and lung cancer patients: motivation to start, experiences and perceived outcomes.

    Science.gov (United States)

    Krebber, Anne-Marie H; van Uden-Kraan, Cornelia F; Melissant, Heleen C; Cuijpers, Pim; van Straten, Annemieke; Becker-Commissaris, Annemarie; Leemans, C René; Verdonck-de Leeuw, Irma M

    2017-01-01

    Recent results of a randomized clinical trial showed that a guided self-help intervention (based on problem-solving therapy) targeting psychological distress among head and neck cancer and lung cancer patients is effective. This study qualitatively explored motivation to start, experiences with and perceived outcomes of this intervention. Data were collected from semi-structured interviews of 16 patients. All interviews were audio-recorded and transcribed verbatim. Data were analyzed individually by two coders and coded into key issues and themes. Patients participated in the intervention for intrinsic (e.g. to help oneself) and for extrinsic reasons (e.g. being asked by a care professional or to help improve health care). Participants indicated positive and negative experiences with the intervention. Several participants appreciated participating as being a pleasant way to work on oneself, while others described participating as too confrontational. Some expressed their disappointment as they felt the intervention had brought them nothing or indicated that they felt worse temporarily, but most participants perceived positive outcomes of the intervention (e.g. feeling less distressed and having learned what matters in life). Cancer patients have various reasons to start a guided self-help intervention. Participants appreciated the guided self-help as intervention to address psychological distress, but there were also concerns. Most participants reported the intervention to be beneficial. The results suggest the need to identify patients who might benefit most from guided self-help targeting psychological distress and that interventions should be further tailored to individual cancer patients' requirements.

  15. Use of healthcare resources and costs associated to the start of treatment with injectable drugs in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Sicras-Mainar, Antoni; Navarro-Artieda, Ruth; Morano, Raúl; Ruíz, Lucía

    2016-12-01

    The main objective was to assess resource use and costs of starting treatment with insulin or injectable GLP-1 receptor analogues (GLP-1 RAs) in a Spanish population of patients with type 2 diabetes mellitus. Treatment adherence and persistence were also determined for both treatment groups. A retrospective, non-interventional, observational study was conducted. Patients aged ≥20 years who started treatment with insulin or GLP-1 RAs in the 2010-2012 period were recruited. Use of healthcare resources was estimated to evaluate healthcare costs in these two groups of patients (medical visits, hospital stay, emergency visits, diagnostic or treatment requests, medication). Clinical information including body mass index (BMI, kg/m 2 ), metabolic control (HbA1c), adherence, persistence, and complications (hypoglycemia, and cardiovascular events (CVE) was collected. The follow-up period was 12 months. Only direct healthcare costs were considered. A total of 1301 patients with a mean age of 67.6 years (51.6% males) were recruited. Of these, 71.9% and 28.1% were on treatment with insulin and GLP-1 RA respectively. After one year of follow-up, patients treated with GLP-1 RAs were found less visits to primary care (8 vs. 11; P<.001) and specialized care (1.0 vs. 1.8; P<.001), hospital stays (0.3 vs. 0.7; P=.030) and less visits to the emergency room (0.8 vs. 1.6; P<.001). Patients treated with GLP-1 showed greater adherence (88.1% vs. 82.7%; P<.001) and persistence (62.0% vs. 55.9%; P=.046), and had less hypoglycemia episodes (13.4% vs. 18.7%; P=.022), with similar metabolic control (HbA1c: 7.2% vs. 7.4%; P=.049), BMI (29.1 vs. 30.9kg/m 2 ), and CVE rate (9.1% vs. 11.5%; P=.330) respectively. The mean corrected direct healthcare cost per patient was €1787 vs. €2005 (P=.046.) CONCLUSIONS: Patients treated with GLP-1 RAs caused lower direct healthcare costs for the National Health System than patients treated with insulin. The results may be explained by greater treatment

  16. Can Free Water Transport Be Used as a Clinical Parameter for Peritoneal Fibrosis in Long-Term PD Patients?

    Science.gov (United States)

    Krediet, Raymond T; Lopes Barreto, Deirisa; Struijk, Dirk G

    2016-01-01

    Sodium sieving in peritoneal dialysis (PD) occurs in a situation with high osmotically-driven ultrafiltration rates. This dilutional phenomenon is caused by free water transport through the water channel aquaporin-1. It has recently been described that encapsulating peritoneal fibrosis is associated with impaired free water transport, despite normal expression of aquaporin-1. In this review, it will be argued that free water transport can be used for assessment of fibrotic peritoneal alterations, due to the water-binding capacity of collagen. Finally, the consequences for clinical practice will be discussed. Copyright © 2016 International Society for Peritoneal Dialysis.

  17. [PK/PD breakpoints and clinical/bacteriological effects of cefcapene pivoxil fine granules for children at free drug concentrations in pediatric patients with respiratory infection].

    Science.gov (United States)

    Toyonaga, Yoshikiyo; Iwai, Naoichi; Motohiro, Takashi; Sunakawa, Keisuke; Fujii, Ryochi

    2008-06-01

    A post-marketing clinical study was previously conducted in pediatric patients with respiratory infection to evaluate the pharmacokinetics, efficacy and safety of cefcapene pivoxil (CFPN-PI) fine granules for children. Based on the results from this study, we evaluated PK/PD breakpoints and clinical/bacteriological effects of CFPN-PI at free drug concentrations in pediatric patients with respiratory infection to determine an effective and safe dosage regimen of CFPN-PI. The following results were obtained from 61 pediatric patients evaluated in our research. 1) The response rate of pediatric respiratory infection to CFPN-PI was 100% for laryngopharyngitis, 84.6% for acute bronchitis, 100% for tonsillitis, 100% for pneumonia and 95.8% for all. 2) The bacteriological response (eradication rate of Haemophilus influenzae, Streptococcus pyogenes, Moraxella catarrhalis, Streptococcus pneumoniae, etc.) of pediatric respiratory infection to CFPN-PI was 87.5% for laryngopharyngitis, 66.7% for acute bronchitis, 75.0% for tonsillitis, 63.6% for pneumonia and 73.8% for all. 3) The blood concentration simulation demonstrated that the PK/PD breakpoint exceeding the time above MIC (TAM) of 40% after administration of CFPN-PI 3 mg/kg three times daily was 0.27 microg/mL. 4) The pediatric patients with respiratory infection were stratified by the TAM (%) of CFPN-PI into 40% to 100% (TAM > or = 40% group) and 0% to 40% (TAM or = 40% group, and 88.9% and 62.5% in the TAM or = 40% group than in the TAM < 40% group, although the between-group difference was not statistically significant.

  18. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Hauke Rühs

    Full Text Available Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.

  19. Prevalence of Cognitive Impairment Among Peritoneal Dialysis Patients, Impact on Peritonitis and Role of Assisted Dialysis.

    Science.gov (United States)

    Shea, Yat Fung; Lam, Man Fai; Lee, Mi Suen Connie; Mok, Ming Yee Maggie; Lui, Sing-Leung; Yip, Terence P S; Lo, Wai Kei; Chu, Leung Wing; Chan, Tak-Mao

    2016-01-01

    ♦ Chronic renal failure and aging are suggested as risk factors for cognitive impairment (CI). We studied the prevalence of CI among peritoneal dialysis (PD) patients using Montreal Cognitive Assessment (MoCA), its impact on PD-related peritonitis in the first year, and the potential role of assisted PD. ♦ One hundred fourteen patients were newly started on PD between February 2011 and July 2013. Montreal Cognitive Assessment was performed in the absence of acute illness. Data on patient characteristics including demographics, comorbidities, blood parameters, dialysis adequacy, presence of helpers, medications, and the number PD-related infections were collected. ♦ The age of studied patients was 59±15.0 years, and 47% were female. The prevalence of CI was 28.9%. Patients older than 65 years old (odds ratio [OR] 4.88, confidence interval [CI] 1.79 - 13.28 p = 0.002) and with an education of primary level or below (OR 4.08, CI 1.30 - 12.81, p = 0.016) were independent risk factors for CI in multivariate analysis. Patients with PD-related peritonitis were significantly older (p peritonitis among self-care PD patients (OR 2.20, CI 0.65 - 7.44, p = 0.20). When we compared patients with MoCA-defined CI receiving self-care and assisted PD, there were no statistically significant differences between the 2 groups in terms of age, MoCA scores, or comorbidities. There were also no statistically significant differences in 1-year outcome of PD-related peritonitis rates or exit-site infections. ♦ Cognitive impairment is common among local PD patients. Even with CI, peritonitis rate in self-care PD with adequate training is similar to CI patients on assisted PD. Copyright © 2016 International Society for Peritoneal Dialysis.

  20. Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy: a population-based regional cohort study from southern Sweden.

    Science.gov (United States)

    Wallman, Johan K; Jöud, Anna; Olofsson, Tor; Jacobsson, Lennart T H; Bliddal, Henning; Kristensen, Lars E

    2017-05-01

    The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Bionaïve nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-TNF initiation. Matched population references were included for comparison and to adjust for secular trends. The nr-axSpA patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-TNF initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axSpA group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Anti-TNF therapy in nr-axSpA was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  1. Cardiac troponin T predicts occult coronary artery stenosis in patients with chronic kidney disease at the start of renal replacement therapy.

    Science.gov (United States)

    Hayashi, Terumasa; Obi, Yoshitsugu; Kimura, Tomonori; Iio, Ken-Ichiro; Sumitsuji, Satoru; Takeda, Yoshihiro; Nagai, Yoshiyuki; Imai, Enyu

    2008-09-01

    The high prevalence of asymptomatic coronary artery stenosis (CAS) in chronic kidney disease (CKD) has emerged as an important predictor of outcome. However, diagnostic tools that can identify asymptomatic CAS have not yet been established. We investigated whether asymptomatic patients at the initiation of renal replacement therapy (RRT) could be screened using cardiac troponin T (cTnT) and atherosclerotic surrogate markers such as ankle-brachial blood pressure index (ABPI) and intima-media thickness (IMT). Among 142 patients who were about to start RRT, 60 who were asymptomatic underwent coronary evaluation by multi-slice computed tomography (MSCT) and/or coronary angiography (CAG). CAG diagnosed 35 patients (43.8%) as CAS positive and 27 of them had multi-vessel disease. Factors associated with CAS were smoking, elevated cTnT, low ABPI and high IMT. Moreover, the severity of CAS was associated with smoking, cTnT and ABPI. Stepwise logistic regression analyses revealed that cTnT was a powerful predictor of asymptomatic multi-vessel CAS. Receiver operating characteristic analysis documented the usefulness of cTnT as a screening tool with a cut-off point 0.05 ng/ml. The optimal screening tool for multi-vessel CAS was cTnT (sensitivity, 92.6%; 95% CI, 82.7-99.9; specificity, 63.6%; 95% CI, 47.2-80.0). We concluded that cTnT should be measured as part of a strategy for detecting asymptomatic CAS, especially multi-vessel disease in patients with CKD at the start of RRT.

  2. Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies

    Science.gov (United States)

    Boulle, Andrew; Schomaker, Michael; May, Margaret T.; Hogg, Robert S.; Shepherd, Bryan E.; Monge, Susana; Keiser, Olivia; Lampe, Fiona C.; Giddy, Janet; Ndirangu, James; Garone, Daniela; Fox, Matthew; Ingle, Suzanne M.; Reiss, Peter; Dabis, Francois; Costagliola, Dominique; Castagna, Antonella; Ehren, Kathrin; Campbell, Colin; Gill, M. John; Saag, Michael; Justice, Amy C.; Guest, Jodie; Crane, Heidi M.; Egger, Matthias; Sterne, Jonathan A. C.

    2014-01-01

    Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. Conclusions After accounting for under-ascertainment of mortality

  3. Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Andrew Boulle

    2014-09-01

    Full Text Available High early mortality in patients with HIV-1 starting antiretroviral therapy (ART in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.Data from four South African cohorts in which patients lost to follow-up (LTF could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation mortality rate ratios (relative to South Africa, and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America], 20,306 (67%, 9,961 (34%, and 824 (12% were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively. High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa. While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.After accounting for under

  4. Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events.

    Science.gov (United States)

    Läubli, Heinz; Balmelli, Catharina; Kaufmann, Lukas; Stanczak, Michal; Syedbasha, Mohammedyaseen; Vogt, Dominik; Hertig, Astrid; Müller, Beat; Gautschi, Oliver; Stenner, Frank; Zippelius, Alfred; Egli, Adrian; Rothschild, Sacha I

    2018-05-22

    Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined. We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade. We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2 months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population.

  5. The impact of different definitions and reference groups on the prevalence of cognitive impairment: a study in postmenopausal breast cancer patients before the start of adjuvant systemic therapy.

    Science.gov (United States)

    Schilder, Christina M; Seynaeve, Caroline; Linn, Sabine C; Boogerd, Willem; Gundy, Chad M; Beex, Louk V; van Dam, Frits S; Schagen, Sanne B

    2010-04-01

    Several prospective studies into the effects of adjuvant systemic therapy on cognitive functioning suggest that a proportion of breast cancer patients show cognitive deficits already before the start of systemic therapy. Owing to, among others, methodological inconsistency, studies report different rates of this pre-treatment cognitive impairment. We examined the impact of four different criteria of cognitive impairment and two types of reference groups (a study-specific healthy reference group versus published normative data) on the prevalence of cognitive impairment. Two hundred and five postmenopausal breast cancer patients underwent a battery of neuropsychological tests before the start of endocrine therapy, 124 healthy subjects underwent the same tests. Proportions of cognitive impaired patients were calculated for each of four criteria for cognitive impairment, using (1) study-specific healthy controls and (2) published norms of healthy controls as reference groups. The prevalence of cognitive impairment varied greatly with the strictness of the criterion, as expected, but also was dependent on the reference group used. Cognitive impairment, relative to published norms, ranged from 1% for the strictest to 36.6% for the less strict criterion, cognitive impairment relative to study-specific healthy controls, ranged from 13.7 to 45.4% for the same criteria. This study highlights contrasting proportions of cognitive impairment by using different criteria for cognitive impairment and different reference groups. (Dis)advantages of the methods using a criterion for cognitive impairment, and of the use of published norms versus a study-specific reference group are discussed. Copyright 2009 John Wiley & Sons, Ltd.

  6. Immuno-inhibitory PD-L1 can be induced by a peptidoglycan/NOD2 mediated pathway in primary monocytic cells and is deficient in Crohn's patients with homozygous NOD2 mutations.

    Science.gov (United States)

    Hewitt, Rachel E; Pele, Laetitia C; Tremelling, Mark; Metz, Andrew; Parkes, Miles; Powell, Jonathan J

    2012-05-01

    Peptidoglycan (PGN) is a ubiquitous bacterial membrane product that, despite its well known pro-inflammatory properties, has also been invoked in immuno-tolerance of the gastrointestinal tract. PGN-induced mucosal IL-10 secretion and downregulation of Toll like receptors are potential mechanisms of action in the gut but there are few data on tolerogenic adaptive immune responses and PGN. Here, using blood-derived mononuclear cells, we showed that PGN induced marked cell surface expression of PD-L1 but not PD-L2 or CD80/CD86, and specifically in the CD14(+) monocytic fraction. This was reproduced at the gene level with rapid induction (<4 h) and, unlike for LPS stimulation, was still sustained at 24 h. Using transfected and native muramyl dipeptide (MDP), which is a cleavage product of PGN and a specific NOD2 agonist, in assays with wild type cells or those from patients with Crohn's disease carrying the Leu1007 frameshift mutation of NOD2, we showed that (i) both NOD2 dependent and independent signalling (appearing TLR2 mediated) occurred for PGN upregulation of PD-L1 (ii) upregulation is lost in response to MDP in patients with the homozygous mutation and (iii) PD-L1 upregulation was unaffected in patients with heterozygous mutations as previously reported for cytokine responses to MDP. The uptake of PGN and its cleavage products by the intestinal mucosa is well recognised and further work should consider PD-L1 upregulation as one potential mechanism of the commensal flora-driven intestinal immuno-tolerance. Indeed, recent work has shown that loss of PD-L1 signalling in the gut breaks CD8(+) T cell tolerance to self antigen and leads to severe autoimmune enteritis. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Relative survival of peritoneal dialysis and haemodialysis patients

    DEFF Research Database (Denmark)

    Heaf, James G; Wehberg, Sonja

    2014-01-01

    INTRODUCTION: Epidemiological studies consistently show an initial survival advantage for PD patients compared to HD. It has recently been suggested that this is due to the fact that many HD patients are referred late, and start dialysis on an acute, in-patient basis. The present study was perfor...

  8. Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

    Science.gov (United States)

    Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

    2017-12-01

    Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.

    Science.gov (United States)

    Palmerini, Emanuela; Agostinelli, Claudio; Picci, Piero; Pileri, Stefano; Marafioti, Teresa; Lollini, Pier-Luigi; Scotlandi, Katia; Longhi, Alessandra; Benassi, Maria Serena; Ferrari, Stefano

    2017-12-19

    We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome. Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+ 90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was observed for PD-L1(IC)+ cases. Our findings support the hypothesis that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior survival for pts with localized osteosarcoma, while PD-L1 expression is associated with worse survival.

  10. Longitudinal Monitoring of Patients With Chronic Low Back Pain During Physical Therapy Treatment Using the STarT Back Screening Tool.

    Science.gov (United States)

    Medeiros, Flávia Cordeiro; Costa, Leonardo Oliveira Pena; Added, Marco Aurélio Nemitalla; Salomão, Evelyn Cassia; Costa, Lucíola da Cunha Menezes

    2017-05-01

    Study Design Preplanned secondary analysis of a randomized clinical trial. Background The STarT Back Screening Tool (SBST) was developed to screen and to classify patients with low back pain into subgroups for the risk of having a poor prognosis. However, this classification at baseline does not take into account variables that can influence the prognosis during treatment or over time. Objectives (1) To investigate the changes in risk subgroup measured by the SBST over a period of 6 months, and (2) to assess the long-term predictive ability of the SBST when administered at different time points. Methods Patients with chronic nonspecific low back pain (n = 148) receiving physical therapy care as part of a randomized trial were analyzed. Pain intensity, disability, global perceived effect, and the SBST were collected at baseline, 5 weeks, 3 months, and 6 months. Changes in SBST risk classification were calculated. Hierarchical linear regression models adjusted for potential confounders were built to analyze the predictive capabilities of the SBST when administered at different time points. Results A large proportion of patients (60.8%) changed their risk subgroup after receiving physical therapy care. The SBST improved the prediction for all 6-month outcomes when using the 5-week risk subgroup and the difference between baseline and 5-week subgroup, after controlling for potential confounders. The SBST at baseline did not improve the predictive ability of the models after adjusting for confounders. Conclusion This study shows that many patients change SBST risk subgroup after receiving physical therapy care, and that the predictive ability of the SBST in patients with chronic low back pain increases when administered at different time points. Level of Evidence Prognosis, 2b. J Orthop Sports Phys Ther 2017;47(5):314-323. Epub 29 Mar 2017. doi:10.2519/jospt.2017.7199.

  11. Low body weight and type of protease inhibitor predict discontinuation and treatment-limiting adverse drug reactions among HIV-infected patients starting a protease inhibitor regimen: consistent results from a randomized trial and an observational cohort

    DEFF Research Database (Denmark)

    Kirk, O; Gerstoft, J; Pedersen, C

    2001-01-01

    OBJECTIVES: To assess predictors for discontinuation and treatment-limiting adverse drug reactions (TLADR) among patients starting their first protease inhibitor (PI). METHODS: Data on patients starting a PI regimen (indinavir, ritonavir, ritonavir/saquinavir and saquinavir hard gel) in a randomi......OBJECTIVES: To assess predictors for discontinuation and treatment-limiting adverse drug reactions (TLADR) among patients starting their first protease inhibitor (PI). METHODS: Data on patients starting a PI regimen (indinavir, ritonavir, ritonavir/saquinavir and saquinavir hard gel....... Low body weight and initiation of ritonavir relative to other PIs were associated with an increased risk of TLADRs. Very consistent results were found in a randomized trial and an observational cohort....

  12. CDK4/6 inhibitor PD0332991 in glioblastoma treatment: does it have a future?

    Directory of Open Access Journals (Sweden)

    Lisette eSchroder

    2015-11-01

    Full Text Available Glioblastoma is aggressive, highly infiltrating, and the most frequent malignant form of brain cancer. With a median survival time of only 14.6 months, when treated with the standard of care, it is essential to find new therapeutic options. A specific CDK4/6 inhibitor, PD0332991, obtained accelerated approval from the Food and Drug Administration for the treatment of patients with advanced estrogen receptor-positive and HER2-negative breast cancer. Common alterations in the cyclin D1-Cyclin Dependent Kinase 4/6-Retinoblastoma 1 pathway in glioblastoma make PD0332991 also an interesting drug for the treatment of glioblastoma. Promising results in in vitro studies, where patient derived glioblastoma cell lines showed sensitivity to PD0332991, gave motive to start in vivo studies. Outcomes of these studies have been contrasting in terms of PD0332991 efficacy within the brain: more research is necessary to conclude whether CDK4/6 inhibitor can be beneficial in the treatment of glioblastoma.

  13. Illness Beliefs, Treatment Beliefs and Information Needs as Starting Points for Patient Information: The Evaluation of an Intervention for Patients with Depression.

    Science.gov (United States)

    Glattacker, Manuela; Heyduck, Katja; Meffert, Cornelia; Jakob, Teresa

    2018-02-16

    Patients with depression are often dissatisfied with disease- and therapy-related information. The objective of this study was to evaluate an intervention that applied the Common Sense Model to the provision of information during inpatient rehabilitation for patients with depression. The intervention was evaluated in a sequential control group design. Analyses of covariance were used to assess differences between the control and intervention groups. Changes with respect to illness and treatment beliefs (personal control, treatment control, coherence and concerns about medicines), satisfaction with information about medicines, illness and rehabilitation, and depressive burden were selected as primary outcome measures. We observed significant between-group differences indicating the intervention group's superiority in terms of satisfaction with information regarding medicines. However, the two groups' changes during rehabilitation did not differ in terms of the other outcomes. The intervention resulted in patients judging that their medication information needs had been more thoroughly fulfilled than those patients who received care-as-usual information. However, the intervention did not prove to be effective when the other outcome variables are considered. Taken together and bearing in mind the limitations of our study-particularly the non-randomised design-our results should be replicated in a randomised controlled trial.

  14. An observational, cross-sectional study to assess the prevalence of chronic kidney disease in type 2 diabetes patients in India (START -India

    Directory of Open Access Journals (Sweden)

    M Prasannakumar

    2015-01-01

    GFR criteria (<60 mL/min/1.73 m 2 was reported in about 23% while as per UACR criteria (≥30 mg/g it was reported in about 35% patients. Conclusion: This interim analysis results suggests that over 40% of T2DM patients have CKD. Despite this high number of T2DM patients with CKD, eGFR analysis shows there are almost 80% of T2DM patients still have reasonably good renal function (eGFR above 60 ml/min, which ensures less restrictions in selecting oral anti-diabetic drugs. Full study results from Start-India study will provide detail insights into the occurrence of CKD in patients with T2DM in India.

  15. UK Renal Registry 16th annual report: chapter 14 2012 multisite dialysis access audit in England, Northern Ireland and Wales and 2011 PD one year follow-up: national and centre-specific analyses.

    Science.gov (United States)

    Briggs, Victoria; Pitcher, David; Shaw, Catriona; Fluck, Richard; Wilkie, Martin

    2013-01-01

    Dialysis access should be timely, minimise complications and maintain functionality. Good functional access is required for renal replacement therapy (RRT) to be successful. The aim of the combined vascular and peritoneal dialysis access audit was to examine practice patterns with respect to dialysis access and highlight variations in practice between renal centres. The UK Renal Registry collected centre-specific information on vascular and peritoneal access outcome measures including patient demographics, dialysis access type (at start of dialysis and three months after start of dialysis), surgical assessment and access functionality. The combined access audit covered incident haemodialysis (HD) and peritoneal dialysis (PD) patients in 2012 from England, Northern Ireland and Wales. Centres who had reported data on incident PD patients for the previous audit in 2011 were additionally asked to provide one year follow up data for this group. Fifty-one centres in England, Wales and Northern Ireland (representing 82% of all centres) returned data on first access from 3,720 incident HD patients and 1,018 incident PD patients. A strong relationship was seen between surgical assessment and the likelihood of starting HD with an arteriovenous fistula (AVF). Type of first access was related to the length of time known to renal services with higher numbers of AVFs and PD catheters used in patients known to renal services for at least one year. Three month and one year outcomes of HD and PD access were poorly reported. This audit provides information on important patient related outcome measures with the potential to lead to an improvement in access provision. This represents an important advance, however data collection remains suboptimal. There is wide practice variation across the England, Wales and Northern Ireland in provision of both HD and PD access which requires further exploration. © 2014 S. Karger AG, Basel.

  16. Combined conservative surgery, chemotherapy and radiation therapy in treatment of the breast cancer patient: the influence of the interval between surgery and start of irradiation

    International Nuclear Information System (INIS)

    Willers, Henning; Wuerschmidt, F.; Janik, I.; Buenemann, H.; Heilmann, H.-P.

    1996-01-01

    electrons to 60 Gy. In 96% of patients, the total tumor dose was 60 Gy. Supraclavicular and axillary regions were given 50 Gy in 22 patients with extensive axillary metastasis. Results: Five years after start of treatment, actuarial overall survival and disease-free survival (DFS) rates were 86% (95% confidence limits, 76-93%) and 73% (61-83%), respectively. In this time period, there were five local failures (LF) with or without simultaneous regional (RF) or distant failure (DF), translating into an actuarial 5-year LF rate of 8% (3-16%). In 14 patients, RF or DF were the first sites of recurrence. For the endpoints DFS and LF, a number of potential prognostic factors, including age at diagnosis, T-stage, nodal status, resection margins, number of chemotherapy cycles, and S-RT interval, was tested by univariate (logrank test) and multivariate analysis (stepwise Cox's proportional hazard regression). The only significant parameter identified was nodal status. For 0-3 nodes and ≥ 4 nodes, actuarial 5-year DFS rates were 86 and 40%, respectively (p 20 weeks) had no significant influence on DFS or LF rates. In contrast, however, when looking on the endpoint RF/DF, there was a statistically almost significant trend towards increased regional and distant relapse with shortening of the S-RT interval due to the delivery of less than six cycles chemotherapy before onset of radiation therapy: actuarial 5-year RF/DF rates were 34 and 13%, respectively (p = 0.056). In an additional analysis of the pattern of first failure using crude rates at four years, no significant difference could be observed: for ≤20 vs. >20 week intervals, the results were 6 and 8% LF, 26 and 10% RF/DF, 71 and 80% recurrence-free rates, respectively (p > 0.05). Conclusions: In our experience, a delay of start of radiation therapy in order to deliver full course chemotherapy had no adverse effect on local tumor control. We are, however, fully aware of the problems associated with retrospective analysis of

  17. Illustrative cases for monitoring by quantitative analysis of BRAF/NRAS ctDNA mutations in liquid biopsies of metastatic melanoma patients who gained clinical benefits from anti-PD1 antibody therapy.

    Science.gov (United States)

    Seremet, Teofila; Planken, Simon; Schreuer, Max; Jansen, Yanina; Delaunoy, Mélanie; El Housni, Hakim; Lienard, Danielle; Del Marmol, Véronique; Heimann, Pierre; Neyns, Bart

    2018-02-01

    Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma. The cases described exemplify four distinct clinical benefit patterns: rapid and durable complete response (CR), early progression, followed by CR, CR followed by early progression after interrupting treatment and long-term disease stabilization. These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring during anti-PD1 therapy is informative and can be of added value for the monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment. An important advantage of our approach is that using the cartridge system on the Idylla platform for mutation analysis, the results become available the same day 2 h after plasma collection. Therefore, in the future, the ctDNA level can be an element in the clinical management of the patients.

  18. Is Peritonitis Risk Increased in Elderly Patients on Peritoneal Dialysis? Report from the French Language Peritoneal Dialysis Registry (RDPLF).

    Science.gov (United States)

    Duquennoy, Simon; Béchade, Clémence; Verger, Christian; Ficheux, Maxence; Ryckelynck, Jean-Philippe; Lobbedez, Thierry

    2016-01-01

    ♦ This study was carried out to examine whether or not elderly patients on peritoneal dialysis (PD) had an increased risk of peritonitis. ♦ This was a retrospective cohort study based on data from the French Language Peritoneal Dialysis Registry. We analyzed 8,396 incident patients starting PD between January 2003 and December 2010. The end of the observation period was 31 December 2012. Patients were separated into 2 age groups: up to 75 and over of 75 years old. ♦ Among 8,396 patients starting dialysis there were 3,173 patients older than 75. When using a Cox model, no association was found between age greater than 75 years and increased risk of peritonitis (hazard ratio [HR]: 0.97 [0.88 - 1.07]). Diabetes (HR: 1.14 [1.01 - 1.28] and continuous ambulatory PD (HR: 1.13 [1.04 - 1.23]) were significantly associated with a higher risk of peritoneal infection whereas nurse-assisted PD was associated with a lower risk of peritonitis (HR: 0.85 [0.78 - 0.94]. In the analysis restricted to the 3,840 self-care PD patients, there was no association between age older than 75 years and risk of peritonitis. ♦ The risk of peritonitis is not increased in elderly patients on PD in a country where assisted PD is available. Copyright © 2016 International Society for Peritoneal Dialysis.

  19. Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor.

    Science.gov (United States)

    Peled, Michael; Tocheva, Anna S; Sandigursky, Sabina; Nayak, Shruti; Philips, Elliot A; Nichols, Kim E; Strazza, Marianne; Azoulay-Alfaguter, Inbar; Askenazi, Manor; Neel, Benjamin G; Pelzek, Adam J; Ueberheide, Beatrix; Mor, Adam

    2018-01-16

    Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.

  20. Comparison of single and boosted protease inhibitor versus nonnucleoside reverse transcriptase inhibitor-containing cART regimens in antiretroviral-naïve patients starting cART after January 1, 2000

    DEFF Research Database (Denmark)

    Mocroft, A; Horban, A; Clumeck, N

    2006-01-01

    increase) response in antiretroviral-naïve patients starting either a single protease inhibitor (PI; n = 183), a ritonavir-boosted PI regimen (n = 197), or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART regimen (n = 447) after January 1, 2000, and the odds of lack of virologic...... or immunologic response at 3 years after starting cART. METHOD: Cox proportional hazards models and logistic regression. RESULTS: After adjustment, compared to patients taking an NNRTI-regimen, patients taking a single-PI regimen were significantly less likely to achieve a viral load (VL)

  1. Lean start-up

    DEFF Research Database (Denmark)

    Rasmussen, Erik Stavnsager; Tanev, Stoyan

    2016-01-01

    The risk of launching new products and starting new firms is known to be extremely high. The Lean Start-up approach is a way of reducing these risks and enhancing the chances for success by validating the products and services in the market with customers before launching it in full scale. The ma...... and the final business model. In other words: The start-up must first nail the problem together with the customers, then develop the solution and test, and then in the end scale it to a full-grown business model.......The risk of launching new products and starting new firms is known to be extremely high. The Lean Start-up approach is a way of reducing these risks and enhancing the chances for success by validating the products and services in the market with customers before launching it in full scale. The main...

  2. Young women with PD: a group work experience.

    Science.gov (United States)

    Posen, J; Moore, O; Tassa, D S; Ginzburg, K; Drory, M; Giladi, N

    2000-01-01

    Parkinson's Disease (PD) prior to the age of 40 affects between 5-10% of the PD population. The psychosocial changes that patients with early PD encounter, may be more devastating and disabling than the actual motor disability. The paper describes a unique experience in groupwork with young female PD patients treated in the Movement Disorders Unit of the Tel Aviv Sourasky Medical Center. The paper focuses on the special issues which characterized this group's experience: stigma, body and sexual image, and personality traits.

  3. UK Renal Registry 17th Annual Report: Chapter 10 2013 Multisite Dialysis Access Audit in England, Northern Ireland and Wales and 2012 PD One Year Follow-up: National and Centre-specific Analyses.

    Science.gov (United States)

    Rao, Anirudh; Pitcher, David; Fluck, Richard; Kumwenda, Mick

    2015-01-01

    Dialysis access should be timely, minimize complications and maintain functionality. The aim of the second combined vascular and peritoneal dialysis access audit was to examine practice patterns with respect to dialysis access and highlight variations in practice between renal centres. The UK Renal Registry collected centre-specific information on incident vascular and peritoneal dialysis access outcome measures in patients from England, Wales and Northern Ireland (EW&NI), including patient demographics, dialysis access type (at start of dialysis and three months after start of dialysis), surgical assessment and access functionality. Centres who had reported data on incident PD patients for the previous 2012 audit were additionally asked to provide one year follow up data for this group. The findings were compared to the audit measures stated in Renal Association clinical practice guidelines for dialysis access. Fifty-seven centres in EW&NI (representing 92% of all centres) returned data on first access from 3,663 incident HD patients and 1,022 incident PD patients. A strong relationship was seen between surgical assessment and the likelihood of starting HD with an arteriovenous fistula (AVF). Twenty-four centres were at least two standard deviations below the 65% target for incident patients starting haemodialysis on AVF and only eight centres (14%) were within two standard deviations of the 85% target for prevalent haemodialysis patients on AVF. There was wide practice variation across the UK in provision of both HD and PD access which requires further exploration.

  4. The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma.

    Science.gov (United States)

    Gwynn, Morgan E; DeRemer, David L

    2018-01-01

    To summarize and evaluate immunotherapy agents targeting programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) recently approved for the treatment of metastatic urothelial carcinomas (UC). A literature review was performed using PubMed (2012 to June 2017), the American Society of Clinical Oncology abstract databases (2012 to June 2017 Annual Meetings/symposia), and the America Association for Cancer Research symposia (2012 to June 2017). A search using clinicaltrials.gov was conducted to identify studies for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab. English language phase I to III studies assessing PD-1 and PD-L1 in UC were incorporated. Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti-PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. Greater objective response rates seem to be observed in PD-L1-positive patients versus PD-L1-negative patients, but methodologies in this assessment differ among clinical trials. The identification of biomarkers that provide greater insight into patients who positively respond to PD-1/PD-L1 therapies are needed. Treatment options for metastatic UC have expanded to include PD-1/PD-L1 therapies. These agents should be strongly considered as second-line therapy over single-agent chemotherapy for patients who fail or progress after platinum-based treatment.

  5. Plot Description (PD)

    Science.gov (United States)

    Robert E. Keane

    2006-01-01

    The Plot Description (PD) form is used to describe general characteristics of the FIREMON macroplot to provide ecological context for data analyses. The PD data characterize the topographical setting, geographic reference point, general plant composition and cover, ground cover, fuels, and soils information. This method provides the general ecological data that can be...

  6. Starting an aphasia center?

    Science.gov (United States)

    Elman, Roberta J

    2011-08-01

    Starting an aphasia center can be an enormous challenge. This article provides initial issues to review and consider when deciding whether starting a new organization is right for you. Determining the need for the program in your community, the best size and possible affiliation for the organization, and available resources, as well as developing a business plan, marketing the program, and building awareness in the community, are some of the factors that are discussed. Specific examples related to starting the Aphasia Center of California are provided. © Thieme Medical Publishers.

  7. Early Head Start Evaluation

    Data.gov (United States)

    U.S. Department of Health & Human Services — Longitudinal information from an evaluation where children were randomly assigned to Early Head Start or community services as usual;direct assessments and...

  8. FEMA DFIRM Station Start

    Data.gov (United States)

    Minnesota Department of Natural Resources — This table contains information about station starting locations. These locations indicate the reference point that was used as the origin for distance measurements...

  9. Head Start Impact Study

    Data.gov (United States)

    U.S. Department of Health & Human Services — Nationally representative, longitudinal information from an evaluation where children were randomly assigned to Head Start or community services as usual;direct...

  10. Getting started with Unity

    CERN Document Server

    Felicia, Patrick

    2013-01-01

    Getting Started with Unity is written in an easy-to-follow tutorial format.""Getting Started with Unity"" is for[ 3D game developers[/color] who would like to learn how to use Unity3D and become familiar with its core features. This book is also suitable for intermediate users who would like to improve their skills. No prior knowledge of Unity3D is required.

  11. Treatment Dosing Patterns and Clinical Outcomes for Patients with Type 2 Diabetes Starting or Switching to Treatment with Insulin Glargine (300 Units per Milliliter) in a Real-World Setting: A Retrospective Observational Study.

    Science.gov (United States)

    Gupta, Shaloo; Wang, Hongwei; Skolnik, Neil; Tong, Liyue; Liebert, Ryan M; Lee, Lulu K; Stella, Peter; Cali, Anna; Preblick, Ronald

    2018-01-01

    Usage patterns and effectiveness of a longer-acting formulation of insulin glargine at a strength of 300 units per milliliter (Gla-300) have not been studied in real-world clinical practice. This study evaluated differences in dosing and clinical outcomes before and after Gla-300 treatment initiation in patients with type 2 diabetes starting or switching to treatment with Gla-300 to assess whether the benefits observed in clinical trials translate into real-world settings. This was a retrospective observational study using medical record data obtained by physician survey for patients starting treatment with insulin glargine at a strength of 100 units per milliliter (Gla-100) or Gla-300, or switching to treatment with Gla-300 from treatment with another basal insulin (BI). Differences in dosing and clinical outcomes before versus after treatment initiation or switching were examined by generalized linear mixed-effects models. Among insulin-naive patients starting BI treatment, no difference in the final titrated dose was observed in patients starting Gla-300 treatment versus those starting Gla-100 treatment [least-squares (LS) mean 0.43 units per kilogram vs 0.44 units per kilogram; P = 0.77]. Both groups had significant hemoglobin A 1c level reductions (LS mean 1.21 percentage points for Gla-300 and 1.12 percentage points for Gla-100 ; both P per kilogram before switch vs 0.58 units per kilogram after switch; P = 0.02). The mean hemoglobin A 1c level was significantly lower after switching than before switching (adjusted difference - 0.95 percentage points, 95% CI - 1.13 to - 0.78 percentage points ; P per patient-year were significantly lower (relative risk 0.17, 95% CI 0.11-0.26; P < 0.0001). Insulin-naive patients starting Gla-300 treatment had fewer hypoglycemic events, a similar hemoglobin A 1c level reduction, and no difference in insulin dose versus patients starting Gla-100 treatment. Patients switching to Gla-300 treatment from treatment with

  12. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.

    Science.gov (United States)

    2004-04-01

    Treatment with rasagiline mesylate, an irreversible monoamine oxidase type B inhibitor, improves symptoms of early Parkinson disease (PD). Preclinical studies suggest that this compound may also modify the progression of PD. To compare the effects of early and later initiation of rasagiline on progression of disability in patients with PD. Double-blind, parallel-group, randomized, delayed-start clinical trial. Four hundred four subjects with early PD, not requiring dopaminergic therapy, enrolled at 32 sites in the United States and Canada. Subjects were randomized to receive rasagiline, 1 or 2 mg/d, for 1 year or placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months. Change in total Unified Parkinson's Disease Rating Scale score from baseline to 12 months. Three hundred seventy-one subjects were included in the 1-year efficacy analysis. Subjects treated with rasagiline, 2 mg/d, for 1 year had a 2.29-unit smaller increase in mean adjusted total Unified Parkinson's Disease Rating Scale score compared with subjects treated with placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months (P =.01). The mean adjusted difference between the placebo/rasagiline, 2 mg/d, group and those receiving rasagiline, 1 mg/d, for 1 year was -1.82 unit on the Unified Parkinson's Disease Rating Scale score (P =.05). Subjects treated with rasagiline, 2 and 1 mg/d, for 12 months showed less functional decline than subjects whose treatment was delayed for 6 months.

  13. Type of Referral, Dialysis Start and Choice of Renal Replacement Therapy Modality in an International Integrated Care Setting.

    Science.gov (United States)

    Marrón, Belén; Ostrowski, Janusz; Török, Marietta; Timofte, Delia; Orosz, Attila; Kosicki, Andrzej; Całka, Alicja; Moro, Daniela; Kosa, Dezider; Redl, Jenö; Qureshi, Abdul Rashid; Divino-Filho, Jose Carolino

    2016-01-01

    Integrated Care Settings (ICS) provide a holistic approach to the transition from chronic kidney disease into renal replacement therapy (RRT), offering at least both types of dialysis. To analyze which factors determine type of referral, modality provision and dialysis start on final RRT in ICS clinics. Retrospective analysis of 626 patients starting dialysis in 25 ICS clinics in Poland, Hungary and Romania during 2012. Scheduled initiation of dialysis with a permanent access was considered as planned RRT start. Modality information (80% of patients) and renal education (87%) were more frequent (pregression analysis, P start (p≤0.05) was associated with early referral, eGFR >8.2 ml/min, >2 months between information and RRT initiation and with vascular etiology after adjustment for age and gender. "Optimal care," defined as ICS follow-up >12 months plus modality information and P start, occurred in 23%. Despite the high rate of late referrals, information and education were widely provided. However, NP start was high and related to late referral and may explain the low frequency of PD.

  14. [Effect of ERK1/2 Signaling Pathway Inhibitor PD98059 on the Expression of Ras, BRaf, MEK, ERK1/2 in Marrow Nucleated Red Blood Cells of CMS Patients].

    Science.gov (United States)

    Han, Yuan-Fang; Ji, Lin-Hua; Feng, Ting-Ting; Liu, Fang; Cui, Sen; Su, Juan

    2017-10-01

    To investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS). Sixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA, the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in nucleated red blood cells, and the Western blot method was used to detect expression of BRaf, MEK, ERK1, ERK2 protein. PD98059 had no effect on the level of Ras-GTP in each groups. Compared with the blank control group, the expression levels of BRaf, MEK mRNA in DMSO group were not statistically significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L group, the expression level of ERK1/2 mRNA was statistically significant (P=0.001, 0.002). Compared with the blank control group, expression levels of p-BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370, 0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2 protein level in other 4 groups were statistically significant (P values were <0.001, 0.007). PD98059 can up-regulate the expressions of ERK1/2 miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras / Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2 pathway may be involved in the pathogenesis of chronic mountain sickness process.

  15. Getting started with Go

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    No, not the Chinese boardgame, the programming language that ironically Google made difficult to google for. You may have heard of Golang, and are wondering whether you should learn it. The answer is that of course you should, and this talk should explain why and point you at the best resources to get started.

  16. The renaissance starts here

    International Nuclear Information System (INIS)

    Nedderman, John.

    1997-01-01

    The Asian Pacific Basin region has the highest rate of growth of anywhere in the world and its need for electricity is staggering. This is leading, noted a senior Korean official speaking at the 10th Pacific Basin Nuclear Conference, to a ''renaissance of nuclear power'' in Asia. Judging by the optimism in evidence at the conference, perhaps it has already started. (Author)

  17. Smart Start Evaluation Plan.

    Science.gov (United States)

    Bryant, Donna; Burchinal, Margaret; Buysse, Virginia; Kotch, Jonathan; Maxwell, Kelly; Neenan, Peter; Noblit, George; Orthner, Dennis; Peisner-Feinberg, Ellen; Telfair, Joseph

    Smart Start is North Carolina's partnership between state government and local leaders, service providers, and families to better serve children under 6 years of age and their families. This report describes the comprehensive plan to evaluate the state and local goals and objectives of the program, focusing on the components addressing the…

  18. ATLAS starts moving in

    CERN Multimedia

    2004-01-01

    The first large active detector component was lowered into the ATLAS cavern on 1 March. It consisted of the 8 modules forming the lower part of the central barrel of the tile hadronic calorimeter. The work of assembling the barrel, which comprises 64 modules, started the following day.

  19. Getting started with UDOO

    CERN Document Server

    Palazzetti, Emanuele

    2015-01-01

    If you are an Android developer who wants to learn how to use UDOO to build Android applications that are capable of interacting with their surrounding environment, then this book is ideal for you. Learning UDOO is the next great step to start building your first real-world prototypes powered by the Android operating system.

  20. Starting up the upstarts.

    Science.gov (United States)

    Greene, J

    1997-12-20

    Venture capitalists pour $1 billion a year into health care--and that investment may be the most overlooked indicator of new business opportunities. Signs show that companies focused on consolidation and cost-cutting are off the A list for risk capital. Instead, venture capitalists are targeting start-ups that save money on the front lines by truly managing care.

  1. Hemodialysis versus Peritoneal Dialysis: A Comparison of Survival Outcomes in South-East Asian Patients with End-Stage Renal Disease.

    Directory of Open Access Journals (Sweden)

    Fan Yang

    Full Text Available Studies comparing patient survival of hemodialysis (HD and peritoneal dialysis (PD have yielded conflicting results and no such study was from South-East Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD who started dialysis with HD and PD in Singapore.Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641 or PD (n = 230 from 2005-2010 was analyzed using the flexible Royston-Parmar (RP model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease.After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p<0.001, although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28, p<0.001. Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (≤65 years old without diabetes or cardiovascular disease.ESRD patients who initiated dialysis with HD experienced better survival outcomes than those who initiated dialysis with PD in Singapore, although survival outcomes may not differ between the two dialysis modalities in young and healthier patients. These findings are potentially confounded by selection bias, as patients were not randomized to the two dialysis modalities in this cohort study.

  2. Changes in the gastric potential difference during chemotherapy in patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Fabrin, B; Højgaard, L; Mouridsen, H T

    1991-01-01

    Nausea and vomiting are frequent side-effects of intravenous cancer chemotherapy. How these complications were related to the gastric mucosal function was investigated by measuring the gastric mucosal potential difference (PD). Eight patients with metastatic breast cancer receiving chemotherapy...... were investigated. The liquid junction-corrected gastric PD and pH were measured with a newly developed microelectrode. The measurements started half an hour before chemotherapy and continued for 4-5 hours. Nausea, vomiting, psychological stress and sleeping episodes were registered. The initial PD...

  3. Interesting case of G6PD deficiency anemia with severe hemolysis

    Directory of Open Access Journals (Sweden)

    Anupam Chhabra

    2013-01-01

    Full Text Available Severe hemolysis was observed in a critically ill patient with G6Pd deficiency where the causative trigger could not be identified. We describe one young patient with severe hemolysis treated with two cycles of plasmapheresis which proved to be an effective tool in the treatment. The patient presented with diffuse pain abdomen, vomiting, yellowish discoloration of sclera and skin and acute breathlessness. Hemoglobin 5.4 mg/dl and total (T serum bilirubin 17.08 mg/dl: Direct (D 4.10 mg/dl and Indirect (I 12.98 mg/dl. Subsequently patient started passing black color urine. As the patient developed severe hemolysis and the trigger agent of hemolysis was unknown, two cycles of plasmapheresis were performed with the aim to remove unknown causative agent. Consequently no trace of hemolysis was found and patient stabilized. Plasmapheresis can be used to treat G6PD deficient patients with severe hemolysis due to unidentified trigger agent.

  4. Getting started with Simulink

    CERN Document Server

    Zamboni, Luca

    2013-01-01

    This practical and easy-to-understand learning tutorial is one big exciting exercise for students and engineers that are always short on their schedules and want to regain some lost time with the help of Simulink.This book is aimed at students and engineers who need a quick start with Simulink. Though it's not required in order to understand how Simulink works, knowledge of physics will help the reader to understand the exercises described.

  5. Getting started with JUCE

    CERN Document Server

    Robinson, Martin

    2013-01-01

    his book is a fast-paced, practical guide full of step-by-step examples which are easy to follow and implement.This book is for programmers with a basic grasp of C++. The examples start at a basic level, making few assumptions beyond fundamental C++ concepts. Those without any experience with C++ should be able to follow and construct the examples, although you may need further support to understand the fundamental concepts.

  6. Getting started with Hazelcast

    CERN Document Server

    Johns, Mat

    2013-01-01

    Written as a step-by-step guide, Getting Started with Hazelcast will teach you all you need to know to make your application data scalable.This book is a great introduction for Java developers, software architects, or developers looking to enable scalable and agile data within their applications. You should have programming knowledge of Java and a general familiarity with concepts like data caching and clustering.

  7. Start-up procedure

    International Nuclear Information System (INIS)

    Marchl, A.; Krebs, W.D.; Aleite, W.

    1975-01-01

    The start-up procedure will be shown on a pressurized water reactor, although most of the activities will occur similarly in other reactor types. The commissioning time can be divided into 5 sections, the phases A to E together lasting 26 months. Subsequently there are a test run of one month and the handling-over of the plant to the operator. A survey of the commissioning sections with several important main events is shown. (orig./TK) [de

  8. Jump Starting Entrepreneurship

    DEFF Research Database (Denmark)

    Burcharth, Ana; Smith, Pernille; Frederiksen, Lars

    How do laid-off employees become entrepreneurs after receiving a dream start into self-employment? This question is relevant for policy makers and entrepreneurship researchers alike since it raises the possibility of a reverse entrepreneurial opportunity, in which the chance of becoming an entrep......How do laid-off employees become entrepreneurs after receiving a dream start into self-employment? This question is relevant for policy makers and entrepreneurship researchers alike since it raises the possibility of a reverse entrepreneurial opportunity, in which the chance of becoming...... an entrepreneur emerges before the discovery of a profitable opportunity. We empirically examine this question on the unique setting of a corporate entrepreneurship program. In the midst of a corporate crisis, Nokia supported laid-off employees to start their own ventures under favorable conditions. We...... persevered in their endeavors and eventually became comfortable with their new career prospects. We discuss the psychological factors that impact career transition after organizational closure and theorize weather they encourage or discourage entrepreneurship....

  9. Decrease in sick leave among patients with rheumatoid arthritis in the first 12 months after start of treatment with tumour necrosis factor antagonists: a population-based controlled cohort study.

    Science.gov (United States)

    Olofsson, Tor; Englund, Martin; Saxne, Tore; Jöud, Anna; Jacobsson, Lennart T H; Geborek, Pierre; Allaire, Saralynn; Petersson, Ingemar F

    2010-12-01

    To investigate the effect of tumour necrosis factor (TNF) antagonist treatment of patients with rheumatoid arthritis (RA) on sick leave (SL) and disability pension (DP) in a population-based setting in southern Sweden. All patients with RA in the South Swedish Arthritis Treatment Group register living in the county of Skåne (population 1.2 million), who started their first treatment with a TNF antagonist between January 2004 and December 2007 and were 18-58 years at treatment start (n = 365), were identified. For each patient with RA, four matched reference subjects from the general population were randomly selected. Data were linked to the Swedish Social Insurance Agency register and the point prevalence of SL and DP as well as days of SL and DP per month were calculated from 360 days before until 360 days after treatment start. At treatment start 38.6% of the patients with RA were registered for SL. During the first 6 months this share dropped to 28.5% (decrease by 26.2%, ptreatment year. Comparing patients with RA to the reference group the relative risk of being on SL was 6.6 (95% CI 5.2 to 8.5) at initiation of anti-TNF treatment and 5.2 (95% CI 4.0 to 6.8) 1 year after that. The corresponding figures for DP were 3.4 (95% CI 2.7 to 4.2) and 3.2 (95% CI 2.7 to 3.9). There was a marked decline in SL during the first 6 months of TNF antagonist treatment in patients with RA in southern Sweden, maintained throughout the first year, which was not offset by a corresponding increase in DP.

  10. Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study

    DEFF Research Database (Denmark)

    Tsakiris, D.J.; Stel, V.S.; Finne, P.

    2010-01-01

    Background. Information on demographics and survival of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this study was to describe the incidence, characteristics, causes...... causes (non-MM) was observed overtime. Patient survival on RRT was examined, unadjusted and adjusted for age and gender. Results. Of the 159 637 patients on RRT, 2453 (1.54%) had MM or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and gender, increased from 0.70 pmp in 1986...

  11. Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment

    Science.gov (United States)

    This pyrethroid insecticide parameter review is an extension of our interest in developing quantitative structure–activity relationship–physiologically based pharmacokinetic/pharmacodynamic (QSAR-PBPK/PD) models for assessing health risks, which interest started with the organoph...

  12. En god start

    DEFF Research Database (Denmark)

    Sievertsen, Hans Henrik

    I Danmark er det muligt at afvige fra reglen om, at barnet skal starte i skole det kalenderår, hvor barnet fylder 6 år. Det gør 10-15 procent af en årgang, mens 80-90 procent af børnene følger normen, og 2-3 procent starter i skole et år tidligere end normen, viser en analyse baseret på børn født i...

  13. Getting Started with Processing

    CERN Document Server

    Reas, Casey

    2010-01-01

    Learn computer programming the easy way with Processing, a simple language that lets you use code to create drawings, animation, and interactive graphics. Programming courses usually start with theory, but this book lets you jump right into creative and fun projects. It's ideal for anyone who wants to learn basic programming, and serves as a simple introduction to graphics for people with some programming skills. Written by the founders of Processing, this book takes you through the learning process one step at a time to help you grasp core programming concepts. You'll learn how to sketch wi

  14. Getting started with Arduino

    CERN Document Server

    Banzi, Massimo

    2011-01-01

    Arduino is the open-source electronics prototyping platform that's taken the design and hobbyist world by storm. This thorough introduction, updated for Arduino 1.0, gives you lots of ideas for projects and helps you work with them right away. From getting organized to putting the final touches on your prototype, all the information you need is here! Inside, you'll learn about: Interaction design and physical computingThe Arduino hardware and software development environmentBasics of electricity and electronicsPrototyping on a solderless breadboardDrawing a schematic diagram Getting started

  15. Getting Started with Netduino

    CERN Document Server

    Walker, Chris

    2012-01-01

    Start building electronics projects with Netduino, the popular open source hardware platform that's captured the imagination of makers and hobbyists worldwide. This easy-to-follow book provides the step-by-step guidance you need to experiment with Netduino and the .NET Micro Framework. Through a set of simple projects, you'll learn how to create electronic gadgets-including networked devices that communicate over TCP/IP. Along the way, hobbyists will pick up the basics of .NET programming, and programmers will discover how to work with electronics and microcontrollers. Follow the projects in

  16. Type of Referral, Dialysis Start and Choice of Renal Replacement Therapy Modality in an International Integrated Care Setting.

    Directory of Open Access Journals (Sweden)

    Belén Marrón

    Full Text Available Integrated Care Settings (ICS provide a holistic approach to the transition from chronic kidney disease into renal replacement therapy (RRT, offering at least both types of dialysis.To analyze which factors determine type of referral, modality provision and dialysis start on final RRT in ICS clinics.Retrospective analysis of 626 patients starting dialysis in 25 ICS clinics in Poland, Hungary and Romania during 2012. Scheduled initiation of dialysis with a permanent access was considered as planned RRT start.Modality information (80% of patients and renal education (87% were more frequent (p8.2 ml/min, >2 months between information and RRT initiation and with vascular etiology after adjustment for age and gender. "Optimal care," defined as ICS follow-up >12 months plus modality information and P start, occurred in 23%.Despite the high rate of late referrals, information and education were widely provided. However, NP start was high and related to late referral and may explain the low frequency of PD.

  17. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-01-01

    INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

  18. 103Pd decay

    International Nuclear Information System (INIS)

    Belyavenko, V.S.; Borozenets, G.P.; Vishnevskij, I.N.; Zheltonozhskij, V.A.

    1986-01-01

    103 Pd decay in different chemical states has been investigated. The change of the partial half-life period equal to 0.67±0.15% has been detected. The γ-spectrum has been measured to a high precision. The new data have been obtained on population probabilities of 103 Rh excited states and the total energy of decay for 103 Pd has been determined to a high precision (543.0±0.8). The values of log ft have been determined

  19. PD-1 Checkpoint Inhibitor Associated Autoimmune Encephalitis

    Directory of Open Access Journals (Sweden)

    Stephanie Schneider

    2017-05-01

    Full Text Available Objective: To report first-hand narrative experience of autoimmune encephalitis and to briefly review currently available evidence of autoimmune encephalitis in cancer patients treated with immune checkpoint inhibitors. Setting: A case study is presented on the management of a patient who developed autoimmune encephalitis during nivolumab monotherapy occurring after 28 weeks on anti-PD-1 monotherapy (nivolumab 3 mg/kg every 2 weeks for non-small cell lung cancer. Results: No substantial improvement was observed by antiepileptic treatment. After administration of 80 mg methylprednisolone, neurologic symptoms disappeared within 24 h and the patient fully recovered. Conclusions: Immune checkpoint inhibitor treatment can lead to autoimmune encephalitis. Clinical trial data indicate a frequency of autoimmune encephalitis of ≥0.1 to <1% with a higher probability during combined or sequential anti-CTLA-4/anti-PD-1 therapy than during anti-PD-1 or anti-PD-L1 monotherapy. Further collection of evidence and translational research is warranted.

  20. Body Weight and Body Mass Index in Patients with End-Stage Cystic Fibrosis Stabilize After the Start of Enteral Tube Feeding

    NARCIS (Netherlands)

    Kraaijeveld, FM; de Roos, N.M.; Belle-van Meerkerk, Gerdien; Teding van Berkhout, F; Heijerman, HGM; van de Graaf, EA

    2017-01-01

    Abstract BACKGROUND: Enteral tube feeding (ETF) is widely used in patients with cystic fibrosis (CF) and end-stage lung disease, but previous studies have been limited to investigating whether ETF improves outcomes in patients with moderately or mildly impaired pulmonary function. OBJECTIVE: This

  1. Body Weight and Body Mass Index in Patients with End-Stage Cystic Fibrosis Stabilize After the Start of Enteral Tube Feeding

    NARCIS (Netherlands)

    Hollander, Francis M.; Roos, de Nicole M.; Belle-Van Meerkerk, Gerdien; Teding van Berkhout, Ferdinand; Heijerman, Harry G.M.; Graaf, van de Ed A.

    2017-01-01

    Background: Enteral tube feeding (ETF) is widely used in patients with cystic fibrosis (CF) and end-stage lung disease, but previous studies have been limited to investigating whether ETF improves outcomes in patients with moderately or mildly impaired pulmonary function. Objective: This study

  2. Time since start of first-line therapy as a predictive clinical marker for nintedanib in patients with previously treated non-small cell lung cancer

    DEFF Research Database (Denmark)

    Gaschler-Markefski, Birgit; Sikken, Patricia; Heymach, John V

    2017-01-01

    INTRODUCTION: No predictive clinical or genetic markers have been identified or validated for antiangiogenic agents in lung cancer. We aimed to identify a predictive clinical marker of benefit for nintedanib, an angiokinase inhibitor, using data from two large second-line non-small cell lung cancer...... Phase III trials (LUME-Lung 1 ([LL1] and LUME-Lung 2). METHODS: Predictive marker identification was conducted in a multi-step process using data from both trials; a hypothesis was generated, confirmed and validated. Statistical analyses included a stepwise selection approach, a recursive partitioning...... method and the evaluation of HRs, including treatment-by-covariate interactions. The marker was finally validated using a prospectively defined hierarchical testing procedure and treatment-by-covariate interaction for overall survival (OS) based on LL1. RESULTS: Time since start of first-line therapy...

  3. Use of the new levodopa agent Stalevo (levodopa/carbidopa/entacapone) in the treatment of Parkinson's disease in out-patient clinical practice (the START-M open trial).

    Science.gov (United States)

    Boiko, A N; Batysheva, T T; Minaeva, N G; Babina, L A; Vdovichenko, T V; Zhuravleva, E Yu; Shikhkerimov, R K; Malykhina, E A; Khozova, A A; Zaitsev, K A; Kostenko, E V

    2008-11-01

    Despite the significant symptomatic effects of levodopa, stable 24-h treatment responses are in the vast majority of patients replaced 2-3 years from the start of treatment by oscillations in motor symptoms (fluctuation, dyskinesia), amelioration of which requires addition of constant (physiological) stimulation of postsynaptic dopamine receptors. To some extent this is provided by Stalevo, which contains levodopa and two enzyme inhibitors: the DDC inhibitor carbidopa and the COMT inhibitor entacapone. The results obtained in the present study demonstrated the advantages of Stalevo over traditional agents in patients with the "wearing off" and "on-off" phenomena.

  4. Outcome of Early Initiation of Peritoneal Dialysis in Patients with End-Stage Renal Failure

    Science.gov (United States)

    Oh, Kook-Hwan; Hwang, Young-Hwan; Cho, Jung-Hwa; Kim, Mira; Ju, Kyung Don; Joo, Kwon Wook; Kim, Dong Ki; Kim, Yon Su; Ahn, Curie

    2012-01-01

    Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone. PMID:22323864

  5. Tenosynovitis in rheumatoid arthritis patients on biologic treatment

    DEFF Research Database (Denmark)

    Hammer, Hilde Berner; Kvien, Tore K; Terslev, Lene

    2017-01-01

    , clinical and laboratory assessments were performed when starting biologic DMARD (bDMARD) and after 1, 2, 3, 6 and 12 months including bilateral grey-scale (GS) and power Doppler (PD) semi-quantitatively (0-3) scoring of ECU and TP tendons and 18 joints. Changes from baseline to follow-up were explored...... by Wilcoxon signed rank test, associations by Spearman's rank correlations and responses to treatment by Standardised Response Means (SRMs). RESULTS: 157 patients (mean age/disease duration 52.4/10.2 years) were included. ECU/TP tenosynovitis was frequent (baseline GS/PD pathology in 76/50% of patients...

  6. Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.

    Science.gov (United States)

    Bottomley, Andrew; Pe, Madeline; Sloan, Jeff; Basch, Ethan; Bonnetain, Franck; Calvert, Melanie; Campbell, Alicyn; Cleeland, Charles; Cocks, Kim; Collette, Laurence; Dueck, Amylou C; Devlin, Nancy; Flechtner, Hans-Henning; Gotay, Carolyn; Greimel, Eva; Griebsch, Ingolf; Groenvold, Mogens; Hamel, Jean-Francois; King, Madeleine; Kluetz, Paul G; Koller, Michael; Malone, Daniel C; Martinelli, Francesca; Mitchell, Sandra A; Moinpour, Carol M; Musoro, Jammbe; O'Connor, Daniel; Oliver, Kathy; Piault-Louis, Elisabeth; Piccart, Martine; Pimentel, Francisco L; Quinten, Chantal; Reijneveld, Jaap C; Schürmann, Christoph; Smith, Ashley Wilder; Soltys, Katherine M; Taphoorn, Martin J B; Velikova, Galina; Coens, Corneel

    2016-11-01

    Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Starting physiology: bioelectrogenesis.

    Science.gov (United States)

    Baptista, Vander

    2015-12-01

    From a Cartesian perspective of rational analysis, the electric potential difference across the cell membrane is one of the fundamental concepts for the study of physiology. Unfortunately, undergraduate students often struggle to understand the genesis of this energy gradient, which makes the teaching activity a hard task for the instructor. The topic of bioelectrogenesis encompasses multidisciplinary concepts, involves several mechanisms, and is a dynamic process, i.e., it never turns off during the lifetime of the cell. Therefore, to improve the transmission and acquisition of knowledge in this field, I present an alternative didactic model. The design of the model assumes that it is possible to build, in a series of sequential steps, an assembly of proteins within the membrane of an isolated cell in a simulated electrophysiology experiment. Initially, no proteins are inserted in the membrane and the cell is at a baseline energy state; the extracellular and intracellular fluids are at thermodynamic equilibrium. Students are guided through a sequence of four steps that add key membrane transport proteins to the model cell. The model is simple at the start and becomes progressively more complex, finally producing transmembrane chemical and electrical gradients. I believe that this didactic approach helps instructors with a more efficient tool for the teaching of the mechanisms of resting membrane potential while helping students avoid common difficulties that may be encountered when learning this topic. Copyright © 2015 The American Physiological Society.

  8. LEP dismantling starts

    CERN Multimedia

    2000-01-01

    Since the end of November, various teams have been getting stuck into dismantling the LEP accelerator and its four experiments. After making the installations safe, the dismantling and removal of 40,000 tonnes of equipment is underway. Down in the tunnel, it is a solemn moment. It is 10 o'clock on 13 December and Daniel Regin, one of those heading the dismantling work, moves in on a magnet, armed with a hydraulic machine. Surrounded by teams gathered there for a course in dismantling, he makes the first cut into LEP. The great deconstruction has begun. In little over than a year, the accelerator will have been cleared away to make room for its successor, the LHC. The start of the operation goes back to 27 November. Because before setting about the machine with hydraulic shears and monkey wrenches, LEP had first to be made safe - it was important to make sure the machine could be taken apart without risk. All the SPS beam injection systems to LEP were cut off. The fluids used for cooling the magnets and superc...

  9. An impressive start

    CERN Multimedia

    2011-01-01

    This has been an excellent week for the LHC, with a succession of fills rapidly increasing the number of proton bunches to 194 per beam. This has allowed the experiments to reach a peak luminosity of 2.5 × 1032 cm-2s-1, thereby surpassing the record for 2010 where we reached 2.0 × 1032 cm-2s-1. At the time of writing, the integrated luminosity delivered by the LHC in 2011 is around 28 inverse picobarns, which is already more than half of the total 2010 dataset.   These are impressive numbers, but what impresses me most is how quickly the LHC operators are now able to turn the machine around between fills, and how well LHC running has been incorporated into the overall operation of CERN’s accelerator complex. The flexibility of the LHC was illustrated on Thursday when we started a short phase of running at 1.38 TeV per beam, equivalent to the energy-per-nucleon of a lead-ion run. This lower energy data will be used by the experiments, in particular by ALICE, to compare...

  10. ATLAS starts moving in

    CERN Multimedia

    Della Mussia, S

    2004-01-01

    The first large active detector component was lowered into the ATLAS cavern on 1st March. It consisted of the 8 modules forming the lower part of the central barrel of the tile hadronic calorimeter. The work of assembling the barrel, which comprises 64 modules, started the following day. Two road trailers each with 64 wheels, positioned side by side. This was the solution chosen to transport the lower part of the central barrel of ATLAS' tile hadronic calorimeter from Building 185 to the PX16 shaft at Point 1 (see Figure 1). The transportation, and then the installation of the component in the experimental cavern, which took place over three days were, to say the least, rather spectacular. On 25 February, the component, consisting of eight 6-metre modules, was loaded on to the trailers. The segment of the barrel was transported on a steel support so that it wouldn't move an inch during the journey. On 26 February, once all the necessary safety checks had been carried out, the convoy was able to leave Buildi...

  11. Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).

    Science.gov (United States)

    Sakaida, Isao; Terai, Shuji; Kurosaki, Masayuki; Yasuda, Moriyoshi; Okada, Mitsuru; Bando, Kosuke; Fukuta, Yasuhiko

    2017-10-01

    Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings. Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6 months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure. Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38 kg on day 7 and -3.52 kg on day 14. Ascites and bloated feeling was significantly improved within 14 days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146 mEq/L was observed in 12 patients (2.7%). In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained. © 2016 The Japan Society of Hepatology.

  12. Factors Associated with the Choice of Peritoneal Dialysis in Patients with End-Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    Pei-Chun Chiang

    2016-01-01

    Full Text Available Background. The purpose of this study was to analyze the factors associated with receiving peritoneal dialysis (PD in patients with incident end-stage renal disease (ESRD in a hospital in Southern Taiwan. Methods. The study included all consecutive patients with incident ESRD who participated in a multidisciplinary predialysis education (MPE program and started their first dialysis therapy between January 1, 2008, and June 30, 2013, in the study hospital. We provided small group teaching sessions to advanced CKD patients and their family to enhance understanding of various dialysis modalities. Multivariate logistic regression models were used to analyze the association of patient characteristics with the chosen dialysis modality. Results. Of the 656 patients, 524 (80% chose hemodialysis and 132 chose PD. Our data showed that young age, high education level, and high scores of activities of daily living (ADLs were positively associated with PD treatment. Patients who received small group teaching sessions had higher percentages of PD treatment (30.5% versus 19.5%; P=0.108 and preparedness for dialysis (61.1% versus 46.6%; P=0.090. Conclusion. Young age, high education level, and high ADL score were positively associated with choosing PD. Early creation of vascular access may be a barrier for PD.

  13. `Pd20Sn13' revisited: crystal structure of Pd6.69Sn4.31

    Directory of Open Access Journals (Sweden)

    Wilhelm Klein

    2015-07-01

    Full Text Available The crystal structure of the title compound was previously reported with composition `Pd20Sn13' [Sarah et al. (1981. Z. Metallkd, 72, 517–520]. For the original structure model, as determined from powder X-ray data, atomic coordinates from the isostructural compound Ni13Ga3Ge6 were transferred. The present structure determination, resulting in a composition Pd6.69Sn4.31, is based on single crystal X-ray data and includes anisotropic displacement parameters for all atoms as well as standard uncertainties for the atomic coordinates, leading to higher precision and accuracy for the structure model. Single crystals of the title compound were obtained via a solid-state reaction route, starting from the elements. The crystal structure can be derived from the AlB2 type of structure after removing one eighth of the atoms at the boron positions and shifting adjacent atoms in the same layer in the direction of the voids. One atomic site is partially occupied by both elements with a Pd:Sn ratio of 0.38 (3:0.62 (3. One Sn and three Pd atoms are located on special positions with site symmetry 2. (Wyckoff letter 3a and 3b.

  14. From Head Start to Sure Start: Reflections on Policy Transfer

    Science.gov (United States)

    Welshman, John

    2010-01-01

    This article uses the history of debates over the US Head Start programme (1965), Early Head Start (1994) and the UK Sure Start initiative (1998), as a window on to policy transfer. In all the three, the aim was that early intervention could offer a means of boosting children's educational attainment and of countering the wider effects of poverty…

  15. Correction of estimates of retention in care among a cohort of HIV-positive patients in Uganda in the period before starting ART: a sampling-based approach.

    Science.gov (United States)

    Nyakato, Patience; Kiragga, Agnes N; Kambugu, Andrew; Bradley, John; Baisley, Kathy

    2018-04-20

    The aim of this study was to use a sampling-based approach to obtain estimates of retention in HIV care before initiation of antiretroviral treatment (ART), corrected for outcomes in patients who were lost according to clinic registers. Retrospective cohort study of HIV-positive individuals not yet eligible for ART (CD4 >500). Three urban and three rural HIV care clinics in Uganda; information was extracted from the clinic registers for all patients who had registered for pre-ART care between January and August 2015. A random sample of patients who were lost according to the clinic registers (>3 months late to scheduled visit) was traced to ascertain their outcomes. The proportion of patients lost from care was estimated using a competing risks approach, first based on the information in the clinic records alone and then using inverse probability weights to incorporate the results from tracing. Cox regression was used to determine factors associated with loss from care. Of 1153 patients registered for pre-ART care (68% women, median age 29 years, median CD4 count 645 cells/µL), 307 (27%) were lost according to clinic records. Among these, 195 (63%) were selected for tracing; outcomes were ascertained in 118 (61%). Seven patients (6%) had died, 40 (34%) were in care elsewhere and 71 (60%) were out of care. Loss from care at 9 months was 30.2% (95% CI 27.3% to 33.5%). After incorporating outcomes from tracing, loss from care decreased to 18.5% (95% CI 13.8% to 23.6%). Estimates of loss from HIV care may be too high if based on routine clinic data alone. A sampling-based approach is a feasible way of obtaining more accurate estimates of retention, accounting for transfers to other clinics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Dialysis modality choice in elderly patients with end-stage renal disease

    DEFF Research Database (Denmark)

    Segall, Liviu; Nistor, Ionuţ; Van Biesen, Wim

    2017-01-01

    on comprehensive and unbiased information. A multidisciplinary team should review elderly patients starting on dialysis, aiming to identify possible barriers to PD and home HD, including physical, visual, cognitive, psychological and social problems, and to overcome such barriers by adequate care, education...

  17. Impact of chronic Immune Thrombocytopenic Purpura (ITP on health-related quality of life: a conceptual model starting with the patient perspective

    Directory of Open Access Journals (Sweden)

    George James N

    2008-02-01

    Full Text Available Abstract Background Immune thrombocytopenic purpura (ITP, a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL. Methods A literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP. Published literature was reviewed to identify key HRQoL issues and existing questionnaires used to assess HRQoL. Focus group transcripts were reviewed, and common themes were extracted by grouping conceptual categories that described the impact on HRQoL. Results The literature synthesis and themes from the focus group data suggest that decreased platelet counts, disease symptoms, and treatment side effects influence multiple domains of HRQoL for ITP patients. Key areas affected by ITP and its treatments include emotional and functional health, work life, social and leisure activities, and reproductive health. Conclusion ITP affects various areas of HRQoL. This conceptual model will help inform the evaluation of therapeutic strategies for ITP.

  18. Glucose-6-phosphate dehydrogenase (G6PD mutations and haemoglobinuria syndrome in the Vietnamese population

    Directory of Open Access Journals (Sweden)

    Day Nick

    2009-07-01

    Full Text Available Abstract Background In Vietnam the blackwater fever syndrome (BWF has been associated with malaria infection, quinine ingestion and G6PD deficiency. The G6PD variants within the Vietnamese Kinh contributing to the disease risk in this population, and more generally to haemoglobinuria, are currently unknown. Method Eighty-two haemoglobinuria patients and 524 healthy controls were screened for G6PD deficiency using either the methylene blue reduction test, the G-6-PDH kit or the micro-methaemoglobin reduction test. The G6PD gene variants were screened using SSCP combined with DNA sequencing in 82 patients with haemoglobinuria, and in 59 healthy controls found to be G6PD deficient. Results This study confirmed that G6PD deficiency is strongly associated with haemoglobinuria (OR = 15, 95% CI [7.7 to 28.9], P G6PD variants were identified in the Vietnamese population, of which two are novel (Vietnam1 [Glu3Lys] and Vietnam2 [Phe66Cys]. G6PD Viangchan [Val291Met], common throughout south-east Asia, accounted for 77% of the variants detected and was significantly associated with haemoglobinuria within G6PD-deficient ethnic Kinh Vietnamese (OR = 5.8 95% CI [114-55.4], P = 0.022. Conclusion The primary frequency of several G6PD mutations, including novel mutations, in the Vietnamese Kinh population are reported and the contribution of G6PD mutations to the development of haemoglobinuria are investigated.

  19. Global differences in dialysis modality mix: the role of patient characteristics, macroeconomics and renal service indicators.

    Science.gov (United States)

    van de Luijtgaarden, Moniek W M; Jager, Kitty J; Stel, Vianda S; Kramer, Anneke; Cusumano, Ana; Elliott, Robert F; Geue, Claudia; MacLeod, Alison M; Stengel, Benedicte; Covic, Adrian; Caskey, Fergus J

    2013-05-01

    An increase in the dialysis programme expenditure is expected in most countries given the continued rise in the number of people with end-stage renal disease (ESRD) globally. Since chronic peritoneal dialysis (PD) therapy is relatively less expensive compared with haemodialysis (HD) and because there is no survival difference between PD and HD, identifying factors associated with PD use is important. Incidence counts for the years 2003-05 were available from 36 countries worldwide. We studied associations of population characteristics, macroeconomic factors and renal service indicators with the percentage of patients on PD at Day 91 after starting dialysis. With linear regression models, we obtained relative risks (RRs) with 95% confidence intervals (CIs). The median percentage of incident patients on PD was 12% (interquartile range: 7-26%). Determinants independently associated with lower percentages of patients on PD were as follows: patients with diabetic kidney disease (per 5% increase) (RR 0.93; 95% CI 0.89-0.97), health expenditure as % gross domestic product (per 1% increase) (RR 0.93; 95% CI 0.87-0.98), private-for-profit share of HD facilities (per 1% increase) (RR 0.996; 95% CI 0.99-1.00; P = 0.04), costs of PD consumables relative to staffing (per 0.1 increase) (RR 0.97; 95% CI 0.95-0.99). The factors associated with a lower percentage of patients on PD include higher diabetes prevalence, higher healthcare expenditures, larger share of private-for-profit centres and higher costs of PD consumables relative to staffing. Whether dialysis modality mix can be influenced by changing healthcare organization and funding requires additional studies.

  20. Analysis of equivalent dose (H) starting from the exposition (X) received for patient families in myocardial perfusion study with 99mTc-Sestamibi

    International Nuclear Information System (INIS)

    Martinez H, I.; Vazquez E, R.; Jimenez A, L.

    2010-09-01

    The myocardial perfusion study with 99m Tc-Sestamibi has the major indication frequency for the coronary arterial illness diagnostic, due to its high sensibility and specificity. The patient families that are exposed to this study also receive the radiation of the injected radiopharmaceutical. The punctual source model (Psm) is generally used for the absorbed dose calculation of the radiation coming from patients under any procedure with radiopharmaceuticals. The objective of this study was to compare the equivalent doses calculated theoretically (Dat) by means of Psm, regarding the measurements that routinely are made by means of a detector Geiger (Dam), as well as to quantify the maxim equivalent dose to which they are exposed the families of the subjected patients to this procedure. 30 voluntary patients were evaluated with clinical indication for myocardial perfusion study with 99m Tc-Sestamibi with acquisition protocol of 1 day: Rest-effort, with dose of 15-30 mCi (555-1110 mBq) respectively. Immediate to each injection of 99m Tc-Sestamibi was calculated the Dat, using the equation that the Psm describes, considering a distance of 1 meter; and the exposition speed was measured by means of a detector Geiger at a distance 1 meter to the heart height. The measurements comparison (Dat vs Dam) was realized by means of the test statistical t-student for independent samples, considering a significance level p≤0.05. For the data of the second injection, was realized a regression analysis to evaluate the lineal correlation among both measurements. Immediately after the injection of 15 mCi (555 mBq) of 99m Tc-Sestamibi, the values of the Dam (1.37±0.43 mrem, 13.7±4.3 μSv) they differ significantly of the Dat (1.04 mrem, p 99m Tc-Sestamibi was carried out in an average time of 2.57±0.02 hr, having the patients group a calculated initial activity of 11.14±0.76 mCi (412.2±28.12 mBq). Differences were not observed statistically significant between the Dam (2.76±0

  1. Comparative evaluation of safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus: Indian multicentric randomized trial - START Study

    Directory of Open Access Journals (Sweden)

    T V Devarajan

    2017-01-01

    Full Text Available Background and Objective: Modern sulfonylureas like glimepiride offer effective glycemic control with extrapancreatic benefits and good tolerability. The objective of the present study was to evaluate and compare safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus (T2DM. Methods: In this open-label, randomized, comparative, multicenter study, a total of 305 T2DM patients who were either drug naïve or uncontrolled on metformin were randomized to glimepiride 1 or 2 mg/sustained-release metformin 1000 mg once daily (glimepiride group, n = 202 or sitagliptin 50 mg/metformin 500 mg twice daily (sitagliptin group, n = 103 for 12 weeks. Primary endpoint was change in glycosylated hemoglobin (HbA1c. Secondary endpoints were change in fasting plasma glucose (FPG, postprandial plasma glucose (PPG, body mass index (BMI and to assess overall safety profile. Results: At 12 weeks, there was a statistically significant difference in the mean HbA1c reduction in glimepiride group (0.42% as compared to sitagliptin group (0.30% (P = 0.001. Mean reduction in FPG and PPG was also statistically significant in the glimepiride group as compared to the sitagliptin group (P = 0.008. There was no significant difference in terms of change in BMI (0.07 ± 0.39 kg/m2 vs. 0.08 ± 0.31 kg/m2 in glimepiride and sitagliptin groups, respectively, (P = 0.644 between both the groups. The incidences of hypoglycemic events were also comparable among both the groups. Conclusion: In T2DM patients, glimepiride/metformin combination exhibited significant reduction in glycemic parameters as compared to sitagliptin/metformin combination. Moreover, there was no significant difference between both the groups in terms of change in BMI and incidence of hypoglycemia.

  2. Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors

    Directory of Open Access Journals (Sweden)

    Shifaa M. Abdin

    2018-01-01

    Full Text Available Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1, and its ligand, programmed death-ligand 1 (PD-L1, via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

  3. Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors.

    Science.gov (United States)

    Abdin, Shifaa M; Zaher, Dana M; Arafa, El-Shaimaa A; Omar, Hany A

    2018-01-25

    Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs) might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

  4. A Minority of Patients Newly Diagnosed with AIDS Are Started on Antiretroviral Therapy at the Time of Diagnosis in a Large Public Hospital in the Southeastern United States.

    Science.gov (United States)

    Goswami, Neela D; Colasanti, Jonathan; Khoubian, Jonathan J; Huang, Yijian; Armstrong, Wendy S; Del Rio, Carlos

    Prompt antiretroviral therapy (ART) initiation after AIDS diagnosis, in the absence of certain opportunistic infections such as tuberculosis and cryptococcal meningitis, delays disease progression and death, but system barriers to inpatient ART initiation at large hospitals in the era of modern ART have been less studied. We reviewed hospitalizations for persons newly diagnosed with AIDS at Grady Memorial Hospital in Atlanta, Georgia in 2011 and 2012. Individual- and system-level variables were collected. Logistic regression models were used to estimate the odds ratios (ORs) for ART initiation prior to discharge. With Georgia Department of Health surveillance data, we estimated time to first clinic visit, ART initiation, and viral suppression. In the study population (n = 81), ART was initiated prior to discharge in 10 (12%) patients. Shorter hospital stay was significantly associated with lack of ART initiation at the time of HIV diagnosis (8 versus 24 days, OR: 1.14, 95% confidence interval: 1.04-1.25). Reducing barriers to ART initiation for newly diagnosed HIV-positive patients with short hospital stays may improve time to viral suppression.

  5. Assessing the relative potency of (S)- and (R)-warfarin with a new PK-PD model, in relation to VKORC1 genotypes.

    Science.gov (United States)

    Ferrari, Myriam; Pengo, Vittorio; Barolo, Massimiliano; Bezzo, Fabrizio; Padrini, Roberto

    2017-06-01

    The purpose of this study is to develop a new pharmacokinetic-pharmacodynamic (PK-PD) model to characterise the contribution of (S)- and (R)-warfarin to the anticoagulant effect on patients in treatment with rac-warfarin. Fifty-seven patients starting warfarin (W) therapy were studied, from the first dose and during chronic treatment at INR stabilization. Plasma concentrations of (S)- and (R)-W and INRs were measured 12, 36 and 60 h after the first dose and at steady state 12-14 h after dosing. Patients were also genotyped for the G>A VKORC1 polymorphism. The PK-PD model assumed a linear relationship between W enantiomer concentration and INR and included a scaling factor k to account for a different potency of (R)-W. Two parallel compartment chains with different transit times (MTT 1 and MTT 2 ) were used to model the delay in the W effect. PD parameters were estimated with the maximum likelihood approach. The model satisfactorily described the mean time-course of INR, both after the initial dose and during long-term treatment. (R)-W contributed to the rac-W anticoagulant effect with a potency of about 27% that of (S)-W. This effect was independent of VKORC1 genotype. As expected, the slope of the PK/PD linear correlation increased stepwise from GG to GA and from GA to AA VKORC1 genotype (0.71, 0.90 and 1.49, respectively). Our PK-PD linear model can quantify the partial pharmacodynamic activity of (R)-W in patients contemporaneously exposed to therapeutic (S)-W plasma levels. This concept may be useful in improving the performance of future algorithms aiming at identifying the most appropriate W maintenance dose.

  6. Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice.

    Science.gov (United States)

    Santoro, Maria Mercedes; Di Carlo, Domenico; Armenia, Daniele; Zaccarelli, Mauro; Pinnetti, Carmela; Colafigli, Manuela; Prati, Francesca; Boschi, Andrea; Antoni, Anna Maria Degli; Lagi, Filippo; Sighinolfi, Laura; Gervasoni, Cristina; Andreoni, Massimo; Antinori, Andrea; Mussini, Cristina; Perno, Carlo Federico; Borghi, Vanni; Sterrantino, Gaetana

    2017-09-22

    Virological success (VS) and immunological reconstitution (IR) of antiretroviral-naive HIV-1-infected patients with pre-therapy viral load (VL) >500,000 copies/ml was assessed after 12 months of treatment according to initial drug-class regimens. An observational multicentre retrospective study was performed. VS was defined as the first VL 500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.

  7. Mild parkinsonian signs in the elderly--is there an association with PD? Crossectional findings in 992 individuals.

    Directory of Open Access Journals (Sweden)

    Stefanie Lerche

    Full Text Available Mild parkinsonian signs (MPS are common in the elderly population, and have been associated with vascular diseases, mild cognitive impairment and dementia; however their relation to Parkinson's disease (PD is unclear. Hypothesizing that individuals with MPS may reflect a pre-stage of PD, i.e. a stage in which the nigrostriatal system is already affected although to a milder degree than at the time of PD diagnosis, aim of this study was to evaluate the similarities between MPS and PD.The TREND study is a prospective cross-sectional cohort study in individuals >50 years with biennial assessments designed to identify markers for an earlier diagnosis of Parkinson's and Alzheimer's disease. For this substudy 992 individuals were included for analyses (892 controls, 73 MPS individuals, 27 PD patients. Parameters defining risk of PD (sex, age, positive family history, prodromal markers (hyposmia, REM sleep behavior disorder, depression and autonomic failure as well as quantitative fine motor, axial motor and cognitive parameters were compared between the three cohorts.As expected, PD patients differed from controls with regard to 12 of 15 of the assessed parameters. MPS individuals differed significantly from controls in 12 of the PD-associated parameters, but differed from PD only in 5 parameters.This study shows that individuals with MPS share many prodromal and clinical markers of PD with PD patients, implying that either a common dynamic process or similar constitutional factors occur in MPS individuals and PD patients.

  8. Orthostatic Hypotension in Drug-Naïve Patients with Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Hyo-Jin Bae

    2011-05-01

    Full Text Available Background and Purpose Orthostatic hypotension (OH is known to be present even in patients with early Parkinson’s disease (PD. To affirm the presence of OH and find correlation between OH and other dysautonomic symptoms in PD, this study has done in newly-diagnosed PD patients. Methods Forty-five non-demented patients with no prior history of treatment for PD were recruited (17 men, 63.8 ± 10.1 years of age. All the patients were evaluated for OH before starting medications. Autonomic symptoms were evaluated with structured questionnaires. Clinical characteristics of PD were evaluated (median Hoehn and Yahr stage 2.0 (1–3, 1.3 ± 1.1 years of disease duration, and comorbid medical conditions that could affect blood pressure were also recorded. Results OH was prevalent, and eighteen patients (40% showed orthostatic hypotension, and twenty-seven (60% did not (normotensive group. There was no significant difference in demographic and clinical characteristics between groups. The presence or severity of symptoms of autonomic dysfunction in the OH group also not differed from those of the normotensive group. Conclusions OH was prevalent even in the early stage of PD, and was not related to presence or severity of any other symptoms of autonomic dysfunction. Our findings suggest that clinicians should pay attention to OH from the early stage of disease.

  9. Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomal iron imaging in Parkinson's disease).

    Science.gov (United States)

    Schwarz, Stefan T; Xing, Yue; Naidu, Saadnah; Birchall, Jim; Skelly, Rob; Perkins, Alan; Evans, Jonathan; Sare, Gill; Martin-Bastida, Antonio; Bajaj, Nin; Gowland, Penny; Piccini, Paola; Auer, Dorothee P

    2017-12-14

    Parkinson's disease (PD) is the most common movement disorder in the elderly and is characterised clinically by bradykinesia, tremor and rigidity. Diagnosing Parkinson's can be difficult especially in the early stages. High-resolution nigrosome MRI offers promising diagnostic accuracy of patients with established clinical symptoms; however, it is unclear whether this may help to establish the diagnosis in the early stages of PD, when there is diagnostic uncertainty. In this scenario, a single photon emission CT scan using a radioactive dopamine transporter ligand can help to establish the diagnosis, or clinical follow-up may eventually clarify the diagnosis. A non-invasive, cost-effective diagnostic test that could replace this would be desirable. We therefore aim to prospectively test whether nigrosome MRI is as useful as DaTSCAN to establish the correct diagnosis in people with minor or unclear symptoms suspicious for PD. In a prospective study we will recruit 145 patients with unclear symptoms possibly caused by Parkinson's from three movement disorder centres in the UK to take part in the study. We will record the Movement Disorder Society - Unified Parkinson's Disease Rating Scale, and participants will undergo DaTSCAN and high-resolution susceptibility weighted MRI at a field strength of 3T. DaTSCANs will be assessed visually and semiquantitatively; MRI scans will be visually assessed for signal loss in nigrosome-1 by blinded investigators. We will compare how the diagnosis suggested by MRI compares with the diagnosis based on DaTSCAN and will also validate the diagnosis based on the two tests with a clinical examination performed at least 1 year after the initial presentation as a surrogate gold standard diagnostic test. The local ethics commission (Health Research Authority East Midlands - Derby Research Ethics Committee) has approved this study (REC ref.: 16/EM/0229). The study is being carried out under the principles of the Declaration of Helsinki (64

  10. School Starting Age and Crime

    DEFF Research Database (Denmark)

    Landersø, Rasmus; Nielsen, Helena Skyt; Simonsen, Marianne

    This paper investigates the effects of school starting age on crime while relying on variation in school starting age induced by administrative rules; we exploit that Danish children typically start first grade in the calendar year they turn seven, which gives rise to a discontinuity in children......’s school starting age. Analyses are carried out using register-based Danish data. We find that higher age at school start lowers the propensity to commit crime, but that this reduction is caused by incapacitation while human capital accumulation is unaffected. Importantly, we also find that the individuals...

  11. A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.

    Science.gov (United States)

    Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne-Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria Mercedes

    2014-01-01

    We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%. Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.

  12. The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance

    Directory of Open Access Journals (Sweden)

    Feng YC

    2018-01-01

    Full Text Available Yang-chun Feng,1,2 Wen-li Ji,3 Na Yue,3 Yan-chun Huang,2 Xiu-min Ma1 1Clinical Laboratory Center, The First Affiliated Hospital of Xinjiang Medical University, 2Clinical Laboratory Center, 3Clinical Pathology Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China Background: According to recent clinical observations, deficient DNA mismatch repair (dMMR is capable of improving antitumor effects of the PD-1/PD-L1 pathway, suggesting that dMMR may act as a prognostic indicator of PD-1/PD-L1 antibody drugs. In this study, we examined the dMMR and PD-1/PD-L1 expression, as well as explored the correlation of dMMR status with PD-1/PD-L1 expression in cervical cancer patients, in order to optimize cervical cancer patient selection for PD-1/PD-L1 antibody drug treatment, which is helpful to avoid adverse effects and keep costs manageable. Methods: Sixty-six tissue samples from patients with squamous cell carcinoma were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of MLH1, MSH2, and PD-L1 in cancer cells were tested by immunohistochemical assay (IHC. Moreover, PD-1/PD-L1 expression in tumor-invading lymphocytes (TILs was detected by IHC as well. Six single-nucleotide-repeat markers of microsatellite instability (MSI, including NR-27, MONO-27, BAT-25, NR-24, NR-21, and BAT-26, were tested by capillary electrophoresis sequencer analysis. According to expression of MLH1, MSH2 and the MSI test, all 66 cases were divided into dMMR or proficient DNA mismatch repair (pMMR groups. The comparisons of dMMR and PD-L1 in cancer cells and of PD-1/PD-L1 in TILs were conducted categorized by age, childbearing history, history of abortion, ethnicity, and cancer cell differentiation subgroup. Furthermore, PD-L1 levels in cancer cells and PD-1/PD-L1 in TILs were analyzed and compared in both dMMR and pMMR subgroups. Results: Of the patient samples, 25

  13. Later Start, Longer Sleep: Implications of Middle School Start Times

    Science.gov (United States)

    Temkin, Deborah A.; Princiotta, Daniel; Ryberg, Renee; Lewin, Daniel S.

    2018-01-01

    Background: Although adolescents generally get less than the recommended 9 hours of sleep per night, research and effort to delay school start times have generally focused on high schools. This study assesses the relation between school start times and sleep in middle school students while accounting for potentially confounding demographic…

  14. Specific brainstem and cortico-spinal reflex abnormalities in coexisting essential tremor and Parkinson's disease (ET-PD).

    Science.gov (United States)

    Yavuz, D; Gündüz, A; Ertan, S; Apaydın, H; Şifoğlu, A; Kiziltan, G; Kiziltan, M E

    2015-05-01

    We aimed to analyze functional changes at brainstem and spinal levels in essential tremor (ET), Parkinson's disease (PD) and coexisting essential tremor and Parkinson's disease (ET-PD). Age- and gender-matched patients with tremor (15 ET, 7 ET with resting tremor, 25 ET-PD and 10 PD) and 12 healthy subjects were enrolled in the study. Diagnosis was established according to standardized clinical criteria. Electrophysiological studies included blink reflex (BR), auditory startle reaction (ASR) and long latency reflex (LLR). Blink reflex was normal and similar in all groups. Probability of ASR was significantly lower in ET-PD group whereas it was similar to healthy subjects in ET and PD (PET, PD and ET-PD groups. LLR III was far more common in the PD group (n=3, 13.6% in ET; n=4, 16.0% in ET-PD and n=7, 46.7% in PD; p=0.037). Despite the integrity of BR pathways, ASR and LLR show distinctive abnormalities in ET-PD. In our opinion, our electrophysiological findings support the hypothesis that ET-PD is a distinct entity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

    Science.gov (United States)

    Pai, Sara I; Jack Lee, J; Carey, Thomas E; Westra, William H; Ferrone, Soldano; Moore, Charles; Mosunjac, Marina B; Shin, Dong M; Ferris, Robert L

    2018-02-01

    Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Tips for Starting Physical Activity

    Science.gov (United States)

    ... Legislative Information Advisory & Coordinating Committees Strategic Plans & Reports Research Areas FAQs ... Starting Physical Activity Related Topics Section Navigation Tips to Help You Get Active ...

  17. Scheduling with target start times

    NARCIS (Netherlands)

    Hoogeveen, J.A.; Velde, van de S.L.; Klein Haneveld, W.K.; Vrieze, O.J.; Kallenberg, L.C.M.

    1997-01-01

    We address the single-machine problem of scheduling n independent jobs subject to target start times. Target start times are essentially release times that may be violated at a certain cost. The goal is to minimize an objective function that is composed of total completion time and maximum

  18. Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2018-04-01

    Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

  19. Encapsulating peritoneal sclerosis in the era of a multi-disciplinary approach based on biocompatible solutions: the NEXT-PD study.

    Science.gov (United States)

    Nakayama, Masaaki; Miyazaki, Masanobu; Honda, Kazuho; Kasai, Kenji; Tomo, Tadashi; Nakamoto, Hidetomo; Kawanishi, Hideki

    2014-01-01

    Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD). Over the past decade in Japan, a multidisciplinary approach has been adopted to minimize the incidence and improve outcomes of EPS. This strategy includes planned PD discontinuation for high-risk patients and the introduction of biocompatible solutions. This study examined the current clinical status of EPS in representative PD centers in Japan. Patients (n = 1,338) from 55 PD centers in Japan who were using neutral-pH solutions from the initiation of therapy (mean age, 62 years; median PD duration, 32 months; concomitant use of icodextrin, 35.2%; PD and hemodialysis combination therapy, 12.2%) were assessed every 6 months to ascertain the reasons for PD discontinuation and the development of EPS development. Outcomes were also recorded. The study period was from November 2008 to March 2012. There were 727 patients who discontinued PD, including 163 deaths. Among all causes of PD withdrawal except for death, planned PD discontinuation to avoid EPS was utilized in 58 cases (7.1% in total). The strategy was increasingly utilized in proportion to the duration of PD: 0.5% for patients undergoing PD for 8 years. Fourteen patients developed EPS (three cases after PD), which corresponded with an overall incidence of 1.0%. The incidence according to the duration of PD was 0.3% for PD 8 years. In terms of therapy, 11 patients were treated with prednisolone (PSL), and surgical enterolysis was utilized in two cases. Complete remission of abdominal symptoms was achieved in twelve patients (85.7%), and three died due to EPS (mortality rate of 21.4%). Use of the multidisciplinary approach described above reduces the risk of the development of EPS according to PD duration. In cases of de novo EPS cases in Japan, this strategy can also attenuate the clinical course of the condition. Copyright © 2014 International Society for Peritoneal Dialysis.

  20. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial

    Science.gov (United States)

    Rizvi, Naiyer A; Mazières, Julien; Planchard, David; Stinchcombe, Thomas E; Dy, Grace K; Antonia, Scott J; Horn, Leora; Lena, Hervé; Minenza, Elisa; Mennecier, Bertrand; Otterson, Gregory A; Campos, Luis T; Gandara, David R; Levy, Benjamin P; Nair, Suresh G; Zalcman, Gérard; Wolf, Jürgen; Souquet, Pierre-Jean; Baldini, Editta; Cappuzzo, Federico; Chouaid, Christos; Dowlati, Afshin; Sanborn, Rachel; Lopez-Chavez, Ariel; Grohe, Christian; Huber, Rudolf M; Harbison, Christopher T; Baudelet, Christine; Lestini, Brian J; Ramalingam, Suresh S

    2015-01-01

    Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in

  1. Movements in Parties: OccupyPD

    Directory of Open Access Journals (Sweden)

    Donatella della Porta

    2015-03-01

    Full Text Available When the United States activists called for people to Occupy#everywhere, it is unlikely they were thinking of the headquarters of the Italian centre-left party. Parties and movements are often considered to be worlds apart. In reality, parties have been relevant players in movement politics, and movements have influenced parties, often through the double militancy of many of their members. OccupyPD testifies to a continuous fluidity at the movement-party border, but also to a blockage in the party’s interactions with society that started long before the economic crisis but drastically accelerated with it. In this paper we present the OccupyPD Movement as a case of interaction between party politics and social movement politics, and in particular between the base membership of a centre-left party and the broader anti-austerity movement that diffused from the US to Europe adopting similar forms of actions and claims. Second, by locating it within the context of the economic and democratic crisis that erupted in 2007, we understand its emergence as a reaction towards politics in times of crisis of responsibility, by which we mean a drastic drop in the capacity of the government to respond to citizens’ requests. To fulfil this double aim, we bridge social movement studies with research on party change, institutional trust and democratic theory, looking at some political effects of the economic crisis in terms of a specific form of legitimacy crisis, as well as citizens’ responses to it, with a particular focus on the political meaning of recent anti-austerity protests. In this analysis, we refer to both quantitative and qualitative data from secondary liter-ature and original in-depth interviews carried out with a sample of OccupyPD activists.

  2. Psychiatric Advance Directives: Getting Started

    Science.gov (United States)

    ... News Legal Issues Search for: About PADs A psychiatric advance directive (PAD) is a legal document that ... decisions during a mental health crisis. Getting Started Psychiatric advance directives (PADs) are relatively new legal instruments ...

  3. Magnetotransport in Pd-rich PdFe alloys

    Czech Academy of Sciences Publication Activity Database

    Kudrnovský, Josef; Drchal, Václav; Turek, Ilja

    2013-01-01

    Roč. 26, č. 5 (2013), s. 1749-1752 ISSN 1557-1939 R&D Projects: GA ČR(CZ) GAP204/11/1228 Institutional support: RVO:68378271 ; RVO:68081723 Keywords : galvanomagnetic transport * Pd-rich PdFe * long-range order * effect of temperature * anisotropic magnetoresistance Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.930, year: 2013

  4. Longitudinal fluctuations in PD1 and PD-L1 expression in association with changes in anti-viral immune response in chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Wenjin Zhang

    2012-08-01

    Full Text Available Abstract Background Controversy exists regarding the role of PD1 and its ligand PD-L1 in chronic hepatitis B infection. In some studies, persistent HBV infection has been attributed to high levels of PD-1 and PD-L1 expression on HBV-specific T-cells and antigen-presenting cells (APCs respectively. Other studies revealed that the up-regulation of PD-1 and PD-L1 during an acute inflammation phase is required to offset increasing positive co-stimulatory signals to avoid severe damage by an over-vigorous immune response. Methods Fifteen chronic hepatitis B patients, with inflammatory flare episode, were recruited prospectively. Based on serum HBV-DNA, HBsAg load, and ALT values, inflammatory flare episode were divided into initial, climax, decline and regression phase. Blood sample and liver biopsy tissues from each individual were taken in these 4 phases respectively. Circulating and intra-hepatic PD1 and PD-L1 expression levels were monitored throughout the inflammatory flare episode by flow cytometry and immunostaining and these expression levels were related to the HBV-specific T-cell changes, expression of pro-inflammatory cytokines, HBV-DNA replication and HBV antigen load. Results ]The levels of PD-1 and PD-L1 expressions were significantly up-regulated in the inflammation ascending phase, initial and climax period and in parallel with HBV-specific colon expansion. It showed increasing the level of serum ALT and decreasing the HBV-DNA loads. As the level of inflammation reduced, the circulating and intra-hepatic PD1 and circulating PD-L1 decreased progressively in concordance with serum ALT, HBV-DNA and HBsAg loads decreased except intra-hepatic PD-1 expression. Intra-hepatic PD-L1 expression did not decrease significantly during the regression phase of inflammation compared to that in prior period. The intra-hepatic PD-L1 expression remained relatively on higher level when serum HBV-DNA load and ALT decreased to approximately normal range

  5. PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma.

    Science.gov (United States)

    Nguyen, Bella Hai; Montgomery, Renn; Fadia, Mitali; Wang, Jiali; Ali, Sayed

    2018-02-01

    There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome. Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity. Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484). Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time. © 2017 John Wiley & Sons Australia, Ltd.

  6. Comparison of the Swedish STarT Back Screening Tool and the Short Form of the Örebro Musculoskeletal Pain Screening Questionnaire in patients with acute or subacute back and neck pain.

    Science.gov (United States)

    Forsbrand, Malin; Grahn, Birgitta; Hill, Jonathan C; Petersson, Ingemar F; Sennehed, Charlotte Post; Stigmar, Kjerstin

    2017-02-21

    Patients with back and neck pain are often seen in primary care and it is important to provide them with tailored interventions based on risk stratification/triage. The STarT Back Screening Tool (SBT) is a widely used screening questionnaire which has not yet been validated for a population with back and/or neck pain with short duration. Our aim was to compare the concurrent validity of the SBT and the short form of the ÖMPSQ including psychometric properties and clinical utility in a primary care setting. Patients who applied for physiotherapy by direct access (January 2013 to January 2014) at 35 primary care centers in south Sweden, with acute or subacute back and/or neck pain, aged 18-67 years, who were not currently on sick leave or had been on sick leave less than 60 days were asked to complete the SBT and ÖMPSQ-short questionnaire (n = 329). We used the Spearman's rank correlations to study correlations, cross tabulation and Cohen's kappa to analyze agreement of patient classification. Clinical utility was described as clinician scoring miscalculations and misclassifications of total and/or subscale scores. Completed SBT (9-items) and ÖMPSQ-short (10-items) data were available for 315/329 patients respectively. The statistical correlation for SBT and ÖMPSQ-short total scores was moderately strong (0.62, p neck pain. SBT seemed to be clinically feasible to use in clinical practice. We therefore suggest that SBT can be used for individuals with both BP and/or NP in primary care settings but it is important to be aware of that SBT's agreement with the ÖMPSQ-short was poor among females aged over 50 years. ClinicalTrials.gov ID: NCT02609750 Registered: November 18, 2015.

  7. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody.

    Science.gov (United States)

    Donahue, Renee N; Lepone, Lauren M; Grenga, Italia; Jochems, Caroline; Fantini, Massimo; Madan, Ravi A; Heery, Christopher R; Gulley, James L; Schlom, Jeffrey

    2017-01-01

    Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers. This study was designed to investigate the effect on immune cell subsets in the peripheral blood of cancer patients prior to and following multiple administrations of avelumab. One hundred twenty-three distinct immune cell subsets in the peripheral blood of cancer patients ( n  = 28) in a phase I trial were analyzed by flow cytometry prior to and following one, three, and nine cycles of avelumab. Changes in soluble (s) CD27 and sCD40L in plasma were also evaluated. In vitro studies were also performed to determine if avelumab would mediate ADCC of PBMC. No statistically significant changes in any of the 123 immune cell subsets analyzed were observed at any dose level, or number of doses, of avelumab. Increases in the ratio of sCD27:sCD40L were observed, suggesting potential immune activation. Controlled in vitro studies also showed lysis of tumor cells by avelumab versus no lysis of PBMC from five donors. These studies demonstrate the lack of any significant effect on multiple immune cell subsets, even those expressing PD-L1, following multiple cycles of avelumab. These results complement prior studies showing anti-tumor effects of avelumab and comparable levels of adverse events with avelumab versus other anti-PD-1/PD-L1 MAbs. These studies provide the rationale to further exploit the potential ADCC mechanism of action of avelumab as well as other human IgG1 checkpoint

  8. Development of 103Pd preparation

    International Nuclear Information System (INIS)

    Tri Murni

    2003-01-01

    Development of 1 03 P d preparation. Radioisotope of 1 03 P d was prepared for medical purpose patient suffering prostate cancer at early stage for therapeutic treatment. In the form of seed, the 1 03 P d radioisotope as a curing agent for prostate cancer is the most effective form with the least side effect. Radioisotope of 1 03 P d is the radioisotope emitting γ of 357 keV. In this investigation 1 03 P d was prepared from natural Pd powder or 1 02 P d enriched bombarded using thermal neutron in the reactor with 1 02 P d( n, γ) 1 03 P d reaction and 1 03 P d radioisotope was obtained. The target was then added with hydrogen peroxide after a with 1N HCl was added followed by drying . Then 2N NH 4 OH was added until the pH of the solution reached 8-10. In every steps of the process, the analysis were performed using MCA while the radiochemical purity were analyses using paper chromatography. The end result of the dissolution process showed that it is an accord with 1 03 P dCl 2 in NH 4 OH solution specification of Nordion

  9. STARTing Again: What Happens After START I Expires?

    International Nuclear Information System (INIS)

    Mladineo, Stephen V.; Durbin, Karyn R.; Eastman, Christina M.

    2007-01-01

    The Strategic Arms Reduction Treaty (START I), a seminal arms control agreement that substantially reduced the levels of deployed strategic nuclear arms in the United States and Russia, will expire in December 2009. At this time, it is unclear what - if anything - will replace it. While the treaty remains relevant, more than a simple extension is appropriate. Instead the authors advocate for a successor regime that builds on the START I legacy but does not rely on the traditional tools of arms control. This paper examines the strategic context in which a successor regime would be developed and proposes several recommendations for future action

  10. Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

    Science.gov (United States)

    Guo, Yanxia; Walsh, Alice M; Canavan, Mary; Wechalekar, Mihir D; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M; Pitzalis, Costantino; Smith, Malcolm D; Friedman, Joshua R; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J; Fearon, Ursula; Nagpal, Sunil

    2018-01-01

    Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

  11. Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

    LENUS (Irish Health Repository)

    Guo, Yanxia

    2018-01-01

    Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA\\/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

  12. CO-induced Pd segregation and the effect of subsurface Pd on CO adsorption on CuPd surfaces

    International Nuclear Information System (INIS)

    Padama, A A B; Villaos, R A B; Albia, J R; Diño, W A; Nakanishi, H; Kasai, H

    2017-01-01

    We report results of our study on the adsorption of CO on CuPd surfaces with bulk stoichiometric and nonstoichiometric layers using density functional theory (DFT). We found that the presence of Pd atoms in the subsurface layer promotes the adsorption of CO. We also observed CO-induced Pd segregation on the CuPd surface and we attribute this to the strong CO–Pd interaction. Lastly, we showed that the adsorption of CO promotes Pd–Pd interaction as compared to the pristine surface which promotes strong Cu–Pd interaction. These results indicate that CO adsorption on CuPd surfaces can be tuned by taking advantage of the CO-induced segregation and by considering the role of subsurface Pd atoms. (paper)

  13. Starting lithium prophylaxis early v. late in bipolar disorder

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh

    2014-01-01

    BACKGROUND: No study has investigated when preventive treatment with lithium should be initiated in bipolar disorder. AIMS: To compare response rates among patients with bipolar disorder starting treatment with lithium early v. late. METHOD: Nationwide registers were used to identify all patients...... with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed lithium during the period 1995-2012 in Denmark (n = 4714). Lithium responders were defined as patients who, following a stabilisation lithium start-up period of 6 months, continued lithium monotherapy without being admitted...... to hospital. Early v. late intervention was defined in two ways: (a) start of lithium following first contact; and (b) start of lithium following a diagnosis of a single manic/mixed episode. RESULTS: Regardless of the definition used, patients who started lithium early had significantly decreased rates of non...

  14. Evaluation of continuous ambulatory peritoneal dialysis fluid C-reactive protein in patients with peritonitis.

    Science.gov (United States)

    Ramanathan, Kumaresan; Padmanabhan, Giri; Vijayaraghavan, Bhooma

    2016-05-01

    Severe peritonitis causing death is one of the most devastating complications of peritoneal dialysis (PD). Since the predictive value of C-reactive protein (CRP) in PD fluid has not been assessed, the objective of the present study is to evaluate its predictive value and clinical correlation in patients on PD with peritonitis. One hundred and twenty patients on continuous ambulatory PD (CAPD) were enrolled and their serum and fluid CRP (Fl. CRP) were evaluated at the start of CAPD. All patients who developed peritonitis were further evaluated for serum and fluid CRP. The patients were categorized into four groups, namely: normal patients (control group), patients with peritonitis, patients with peritonitis leading to catheter removal, and death due to peritonitis. Sixty-five patients developed peritonitis of whom, catheter removal was performed in eight patients. Five patients died due to peritonitis-related complications. Fl. CRP showed a significant difference among the three groups, unlike S. CRP. Estimation of CRP in the peritoneal fluid may be a useful marker to monitor the onset of peritonitis.

  15. Psychogenic and neural visual-cue response in PD dopamine dysregulation syndrome.

    Science.gov (United States)

    Loane, Clare; Wu, Kit; O'Sullivan, Sean S; Lawrence, Andrew D; Woodhead, Zoe; Lees, Andrew J; Piccini, Paola; Politis, Marios

    2015-11-01

    Dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) patients refers to the compulsive use of dopaminergic replacement therapy and has serious psycho-social consequences. Mechanisms underlying DDS are not clear although has been linked to dysfunctional brain reward networks. With fMRI, we investigate behavioral and neural response to drug-cues in six PD DDS patients and 12 PD control patients in both the ON and OFF medication state. Behavioral measures of liking, wanting and subjectively 'feeling ON medication' were also collected. Behaviorally, PD DDS patients feel less ON and want their drugs more at baseline compared to PD controls. Following drug-cue exposure, PD DDS patients feel significantly more ON medication, which correlates with significant increases in reward related regions. The results demonstrate that exposure to drug-cues increases the subjective feeling of being 'ON' medication which corresponds to dysfunctional activation in reward related regions in PD DDS patients. These findings should be extended in future studies. Visual stimuli being sufficient to elicit behavioral response through neuroadaptations could have direct implications to the management of addictive behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-11-01

    The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas

  17. Effects of Conversion to a Bicarbonate/Lactate-Buffered, Neutral-pH, Low-GDP PD Regimen in Prevalent PD: A 2-Year Randomized Clinical Trial.

    Science.gov (United States)

    Farhat, Karima; Douma, Caroline E; Ferrantelli, E; Ter Wee, Pieter M; Beelen, Robert H J; van Ittersum, Frans J

    2017-01-01

    ♦ BACKGROUND: The use of pH-neutral peritoneal dialysis (PD) fluids low in glucose degradation products (GDP) may better preserve the peritoneal membrane and have fewer systemic effects. The effects of conversion from conventional to neutral-pH, low-GDP PD fluids in prevalent patients are unclear. Few studies on the role of neutral-pH, low-GDP PD have studied residual renal function, ultrafiltration, peritonitis incidence and technique failure, transport characteristics, and local and systemic markers of inflammation in prevalent PD patients. ♦ METHODS: In a multi-center open-label randomized clinical trial (RCT), we randomly assigned 40 of 78 stable continuous ambulatory PD (CAPD) and automated PD (APD) patients to treatment with bicarbonate/lactate, neutral-pH, low-GDP PD fluid (Physioneal; Baxter Healthcare Corporation, Deerfield, IL, USA) and compared them with 38 patients continuing their current standard lactate-buffered PD fluid (PDF) (Dianeal; Baxter Healthcare Corporation, Deerfield, IL, USA) during 2 years. Primary outcome was residual renal function (RRF) and ultrafiltration (UF) during peritoneal equilibration test (PET); peritonitis incidence was a secondary outcome. Furthermore, clinical parameters as well as several biomarkers in effluents and serum were measured. ♦ RESULTS: During follow-up, RRF did not differ between the groups. In the Physioneal group ultrafiltration (UF) during PET remained more or less stable (-20 mL [confidence interval (CI): -163.5 - 123.5 mL]; p = 0.7 over 24 months), whereas it declined in the Dianeal group (-243 mL [CI: -376.6 to -109.4 mL]; p GDP PD fluids, although there is a possibility that the study was underpowered to detect a difference. Decline in UF during standardized PET was lower after 2 years in the Physioneal group. Copyright © 2017 International Society for Peritoneal Dialysis.

  18. Start Where Your Students Are

    Science.gov (United States)

    Jackson, Robyn R.

    2010-01-01

    Starting where your students are means understanding how currencies are negotiated and traded in the classroom. Any behavior that students use to acquire the knowledge and skills needed in the classroom functions as currency. Teachers communicate the kinds of currencies they accept in their classrooms, such as getting good grades; students do…

  19. Start-up of Rapsodie

    International Nuclear Information System (INIS)

    Pontier, R.

    1967-01-01

    After giving a general description of Rapsodie this report presents the conditions in which the start-up occurred and in which the tests were carried out. A chronological account is given of the operations and of the main events which occurred. The modifications made to the reactor during this period are described and a synthesis of the results obtained is presented. (author) [fr

  20. When to Start Antiretroviral Therapy

    Science.gov (United States)

    ... illnesses and coinfections Recent HIV infection Pregnancy All pregnant women with HIV should take HIV medicines to prevent mother-to- ... protect the health of the pregnant woman. All pregnant women with HIV should start taking HIV medicines as soon as ...

  1. Head Start Center Design Guide.

    Science.gov (United States)

    Administration for Children, Youth, and Families (DHHS), Washington, DC. Head Start Bureau.

    This guide contains suggested criteria for planning, designing, and renovating Head Start centers so that they are safe, child-oriented, developmentally appropriate, beautiful, environmentally sensitive, and functional. The content is based on the U.S. General Services Administration's Child Care Center Design Guide, PBS-P140, which was intended…

  2. Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.

    Science.gov (United States)

    Lee, Hyun Tae; Lee, Ju Yeon; Lim, Heejin; Lee, Sang Hyung; Moon, Yu Jeong; Pyo, Hyo Jeong; Ryu, Seong Eon; Shin, Woori; Heo, Yong-Seok

    2017-07-17

    In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.

  3. Comparing PD results with visual inspection

    International Nuclear Information System (INIS)

    Rossi, A.; Stone, G.C.

    2005-01-01

    ENEL is the main generation utility in Italy, with more than 200 hydro units and 120 turbine generators, totaling 39,000 MW of capacity. To help identify the maintenance needs of the stator windings in these units, ENEL has been gradually equipping the generators with partial discharge (PD) sensors that facilitate an on-line measurement of the PD. The paper describes results from several machines that have PD. In all cases, the high PD was confirmed by visual inspections. Although PD usually found the units with severe insulation problems, it was not always possible to determine the causes of the deterioration from the PD pattern. (author)

  4. G6PD Deficiency in an HIV Clinic Setting in the Dominican Republic

    Science.gov (United States)

    Xu, Julia Z.; Francis, Richard O.; Lerebours Nadal, Leonel E.; Shirazi, Maryam; Jobanputra, Vaidehi; Hod, Eldad A.; Jhang, Jeffrey S.; Stotler, Brie A.; Spitalnik, Steven L.; Nicholas, Stephen W.

    2015-01-01

    Because human immunodeficiency virus (HIV)-infected patients receive prophylaxis with oxidative drugs, those with glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience hemolysis. However, G6PD deficiency has not been studied in the Dominican Republic, where many individuals have African ancestry. Our objective was to determine the prevalence of G6PD deficiency in Dominican HIV-infected patients and to attempt to develop a cost-effective algorithm for identifying such individuals. To this end, histories, chart reviews, and G6PD testing were performed for 238 consecutive HIV-infected adult clinic patients. The overall prevalence of G6PD deficiency (8.8%) was similar in males (9.3%) and females (8.5%), and higher in Haitians (18%) than Dominicans (6.4%; P = 0.01). By logistic regression, three clinical variables predicted G6PD status: maternal country of birth (P = 0.01) and a history of hemolysis (P = 0.01) or severe anemia (P = 0.03). Using these criteria, an algorithm was developed, in which a patient subset was identified that would benefit most from G6PD screening, yielding a sensitivity of 94.7% and a specificity of 97.2%, increasing the pretest probability (8.8–15.1%), and halving the number of patients needing testing. This algorithm may provide a cost-effective strategy for improving care in resource-limited settings. PMID:26240158

  5. UK Renal Registry 15th annual report: Chapter 8 UK multisite peritoneal dialysis access catheter audit for first PD catheters 2011.

    Science.gov (United States)

    Briggs, Victoria; Pitcher, David; Braddon, Fiona; Fogarty, Damian; Wilkie, Martin

    2013-01-01

    The central paradigm of effective peritoneal dialysis (PD) is an appropriate standard of PD catheter function. The aim of the project was to develop an effective national PD access audit which would identify an 'appropriate standard' of PD catheter function. The UK Renal Registry collected centre specific information on various PD access outcome measures including catheter functionality and post-insertion complications. The first PD access audit covering England, Northern Ireland and Wales was conducted during April to June 2012 looking at incident dialysis patients in 2011. Forty three data collection spreadsheets were returned from a total of 65 centres describing 917 PD catheter placements. The median age of PD patients was 61 years and 61.5% were male. The proportion of patients initiated on PD in comparison to HD was lower in socially deprived areas. There was a relationship between the timing of nephrology referral and the likelihood of surgical assessment regarding PD catheter placement. Patients with diabetes did not have higher rates of PD catheter failure or of early peritonitis. A comparative PD catheter audit has the potential to provide valuable information on an important patient related outcome measure and lead to an improvement in patient experience. There was wide variation between centres of PD catheter use for late presenting patients. Overall patients were more likely to get a PD catheter if they had been known to the service for more than 1 year. The percutaneous insertion technique was associated with a higher early (less than 2 week) peritonitis rate and more catheter flow problems. Copyright © 2013 S. Karger AG, Basel.

  6. PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence

    Directory of Open Access Journals (Sweden)

    Tran PN

    2017-05-01

    Full Text Available Phu N Tran,1* Sarmen Sarkissian,1* Joseph Chao,2 Samuel J Klempner3,4 1Division of Hematology-Oncology, University of California Irvine, Orange, 2Department of Medical Oncology and Developmental Therapeutics, City of Hope, Duarte, 3Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 4The Angeles Clinic and Research Institute, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Gastric adenocarcinoma is a leading cause of global cancer-related morbidity and mortality, and new therapeutic approaches are needed. Despite the improved outcomes with monoclonal antibodies targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor receptor 2, durable responses are uncommon. Targeting immune checkpoints including PD-1, PD-L1 and CTLA-4 have led to improved survival across several tumor types, frequently characterized by prolonged benefit in responding patients. Tumoral and lymphocyte-derived immunohistochemical staining for PD-1, PD-L1, and tumor mutational burden have shown potential as predictive response biomarkers in several tumor types. Optimal incorporation of immune-mediated therapies into gastric cancer (GC is an area of intense ongoing investigation and benefit has been demonstrated in smaller studies of advanced patients. Important questions of biomarker selection, roles for molecular characterization, optimal combinatorial approaches, and therapeutic sequencing remain. In this study, current data are reviewed for immune checkpoint inhibitors in GC, and putative biomarkers, ongoing trials, and future considerations are discussed. Keywords: immunotherapy, stomach cancer, checkpoint inhibitor, nivolumab, pembrolizumab, tumor mutational burden

  7. Color Discrimination in Patients with Gaucher Disease and Parkinson Disease.

    Science.gov (United States)

    Simon-Tov, Shlomi; Dinur, Tama; Giladi, Nir; Bar-Shira, Anat; Zelis, Mayaan; Zimran, Ari; Elstein, Deborah

    2015-01-01

    Poor color discrimination among patients with Parkinson disease (PD) has long been recognized. It has been shown that carrying one or two mutations in the β-glucocerebrosidase gene (GBA) for the autosomal disease Gaucher disease (GD), as based initially on clinical evidence, is a genetic risk factor for early-onset PD. The purpose of this study was to assess color discrimination in patients with one or two GBA mutations relative to healthy controls to ascertain whether this function is affected when persons with GD or even one GBA mutation develop PD. The Farnsworth-Munsell 100 hue test (FMHT) was evaluated among patients with GD+PD compared to patients with GD only, obligate GBA carriers with and without PD, patients with PD only, and healthy controls. FMHT outcome include computer-generated TES (Total Error Score) and values recommended by Vingrys & King-Smith. Six groups of 10 persons were tested. Significant differences were seen for male GD+PD and for age in PD. The highest mean TES was in the PD only group, the lowest in the GD only group. There was a significant difference because of PD in groups with GD and GBA carriers. GD+PD means were between GD only and PD only mean scores. These findings confirm that PD impacts color discrimination, more in males with GD+PD but nonetheless, GD+PD patients (but not GBA carriers) had better scores than PD only patients.

  8. Neonatal nucleated red blood cells in G6PD deficiency.

    Science.gov (United States)

    Yeruchimovich, Mark; Shapira, Boris; Mimouni, Francis B; Dollberg, Shaul

    2002-05-01

    The objective of this study is to study the absolute number of nucleated red blood cells (RBC) at birth, an index of active fetal erythropoiesis, in infants with G6PD deficiency and in controls. We tested the hypothesis that hematocrit and hemoglobin would be lower, and absolute nucleated RBC counts higher, in the G6PD deficient and that these changes would be more prominent in infants exposed passively to fava bean through maternal diet. Thirty-two term infants with G6PD deficiency were compared with 30 term controls. Complete blood counts with manual differential counts were obtained within 12 hours of life. Absolute nucleated RBC and corrected leukocyte counts were computed from the Coulter results and the differential count. G6PD deficient patients did not differ from controls in terms of gestational age, birth weight, or Apgar scores or in any of the hematologic parameters studied, whether or not the mother reported fava beans consumption in the days prior to delivery. Although intrauterine hemolysis is possible in G6PD deficient fetuses exposed passively to fava beans, our study supports that such events must be very rare.

  9. Alternative splice variants of the human PD-1 gene

    DEFF Research Database (Denmark)

    Nielsen, Christian; Ohm-Laursen, Line; Barington, Torben

    2005-01-01

    PD-1 is an immunoregulatory receptor expressed on the surface of activated T cells, B cells, and monocytes. We describe four alternatively spliced PD-1 mRNA transcripts (PD-1Deltaex2, PD-1Deltaex3, PD-1Deltaex2,3, and PD-1Deltaex2,3,4) in addition to the full length isoform. PD-1Deltaex2 and PD-1...... and flPD-1 upon activation suggests an important interplay between the putative soluble PD-1 and flPD-1 possibly involved in maintenance of peripheral self-tolerance and prevention of autoimmunity....

  10. Asymptomatic Effluent Protozoa Colonization in Peritoneal Dialysis Patients.

    Science.gov (United States)

    Simões-Silva, Liliana; Correia, Inês; Barbosa, Joana; Santos-Araujo, Carla; Sousa, Maria João; Pestana, Manuel; Soares-Silva, Isabel; Sampaio-Maia, Benedita

    Currently, chronic kidney disease (CKD) is a global health problem. Considering the impaired immunity of CKD patients, the relevance of infection in peritoneal dialysis (PD), and the increased prevalence of parasites in CKD patients, protozoa colonization was evaluated in PD effluent from CKD patients undergoing PD. Overnight PD effluent was obtained from 49 asymptomatic stable PD patients. Protozoa analysis was performed microscopically by searching cysts and trophozoites in direct wet mount of PD effluent and after staining smears. Protozoa were found in PD effluent of 10.2% of evaluated PD patients, namely Blastocystis hominis, in 2 patients, and Entamoeba sp., Giardia sp., and Endolimax nana in the other 3 patients, respectively. None of these patients presented clinical signs or symptoms of peritonitis at the time of protozoa screening. Our results demonstrate that PD effluent may be susceptible to asymptomatic protozoa colonization. The clinical impact of this finding should be further investigated. Copyright © 2016 International Society for Peritoneal Dialysis.

  11. Getting started with Drupal commerce

    CERN Document Server

    Jones, Richard

    2013-01-01

    A simple yet concise step-by-step tutorial that starts from scratch and builds up your knowledge with focused examples that will enable you to set up and run an e-commerce website.This book is for beginners and will take you through the installation and configuration of Drupal Commerce from scratch, but some familiarity with Drupal 7 will be an advantage. All examples are based on development on a local computer - you do not need a hosted Drupal environment.

  12. Getting started with Twitter Flight

    CERN Document Server

    Hamshere, Tom

    2013-01-01

    Getting Started with Twitter Flight is written with the intention to educate the readers, helping them learn how to build modular powerful applications with Flight, Twitter's cutting-edge JavaScript framework.This book is for anyone with a foundation in JavaScript who wants to build web applications. Flight is quick and easy to learn, built on technologies you already understand such as the DOM, events, and jQuery.

  13. School start times for adolescents.

    Science.gov (United States)

    2014-09-01

    The American Academy of Pediatrics recognizes insufficient sleep in adolescents as an important public health issue that significantly affects the health and safety, as well as the academic success, of our nation's middle and high school students. Although a number of factors, including biological changes in sleep associated with puberty, lifestyle choices, and academic demands, negatively affect middle and high school students' ability to obtain sufficient sleep, the evidence strongly implicates earlier school start times (ie, before 8:30 am) as a key modifiable contributor to insufficient sleep, as well as circadian rhythm disruption, in this population. Furthermore, a substantial body of research has now demonstrated that delaying school start times is an effective countermeasure to chronic sleep loss and has a wide range of potential benefits to students with regard to physical and mental health, safety, and academic achievement. The American Academy of Pediatrics strongly supports the efforts of school districts to optimize sleep in students and urges high schools and middle schools to aim for start times that allow students the opportunity to achieve optimal levels of sleep (8.5-9.5 hours) and to improve physical (eg, reduced obesity risk) and mental (eg, lower rates of depression) health, safety (eg, drowsy driving crashes), academic performance, and quality of life. Copyright © 2014 by the American Academy of Pediatrics.

  14. A prospective, observational study comparing the PK/PD relationships of generic Meropenem (Mercide®) to the innovator brand in critically ill patients.

    Science.gov (United States)

    Mer, Mervyn; Snyman, Jacques Rene; van Rensburg, Constance Elizabeth Jansen; van Tonder, Jacob John; Laurens, Ilze

    2016-01-01

    Clinicians' skepticism, fueled by evidence of inferiority of some multisource generic antimicrobial products, results in the underutilization of more cost-effective generics, especially in critically ill patients. The aim of this observational study was to demonstrate equivalence between the generic or comparator brand of meropenem (Mercide ® ) and the leading innovator brand (Meronem ® ) by means of an ex vivo technique whereby antimicrobial activity is used to estimate plasma concentration of the active moiety. Patients from different high care and intensive care units were recruited for observation when prescribed either of the meropenem brands under investigation. Blood samples were collected over 6 hours after a 30 minute infusion of the different brands. Meropenem concentration curves were established against United States Pharmacopeia standard meropenem (Sigma-Aldrich) by using standard laboratory techniques for culture of Klebsiella pneumoniae. Patients' plasma samples were tested ex vivo, using a disc diffusion assay, to confirm antimicrobial activity and estimate plasma concentrations of the two brands. Both brands of meropenem demonstrated similar curves in donor plasma when concentrations in vials were confirmed. Patient-specific serum concentrations were determined from zones of inhibition against a standard laboratory Klebsiella strain ex vivo, confirming at least similar in vivo concentrations as the concentration curves (90% confidence interval) overlapped; however, the upper limit of the area under the curve for the ratio comparator/innovator exceeded the 1.25-point estimate, i.e., 4% higher for comparator meropenem. This observational, in-practice study demonstrates similar ex vivo activity and in vivo plasma concentration time curves for the products under observation. Assay sensitivity is also confirmed. Current registration status of generic small molecules is in place. The products are therefore clinically interchangeable based on

  15. Impulse control disorder in PD: A lateralized monoaminergic frontostriatal disconnection syndrome?

    Science.gov (United States)

    Premi, E; Pilotto, A; Garibotto, V; Bigni, B; Turrone, R; Alberici, A; Cottini, E; Poli, L; Bianchi, M; Formenti, A; Cosseddu, M; Gazzina, S; Magoni, M; Bertoli, M; Paghera, B; Borroni, B; Padovani, A

    2016-09-01

    Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico-striatal connectivity, especially between left putamen and frontal associative areas. 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM). PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+. the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The combination of anti-KIR monoclonal antibodies with anti-PD-1/PD-L1 monoclonal antibodies could be a critical breakthrough in overcoming tumor immune escape in NSCLC

    Directory of Open Access Journals (Sweden)

    He YY

    2018-04-01

    Full Text Available Yayi He,1,2,* Sangtian Liu,1,* Jane Mattei,3 Paul A Bunn Jr,2 Caicun Zhou,1 Daniel Chan2 1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China; 2Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 3Oncology Department, Moinhos de Vento Hospital, Porto Alegre, Brazil *These authors contributed equally to this work Background: The anti-programmed death-1 (PD-1/programmed death ligand-1 (PD-L1 monoclonal antibody has a good effect in the treatment of non-small cell lung cancer (NSCLC, but not all PD-1/PD-L1 positive patients can get benefit from it. Compensatory expression of other immune checkpoints may be correlated with the poor efficacy of anti-PD-1/PD-L1 monoclonal antibodies. The inhibitory human leukocyte antigen (HLA/killer cell Ig-like receptor (KIR can effectively block the killing effect of natural killer (NK cells on tumors. Our previous studies have confirmed that high expression of KIR was correlated with poor prognosis of NSCLC. Inhibitory KIR expression was positively correlated with the expression of PD-1. Methods: The expressions of KIR 2D (L1, L3, L4, S4 (BC032422/ADQ31987/NP_002246/NP_036446, Abcam and PD-1 (NAT 105, Cell marque proteins was assessed by immunohis­tochemistry. Results: The expression of inhibitory KIR in tumor cells or tumor infiltrating lymphocytes (TILs is associated with PD-1 expression. Among PD-1 positive patients, 76.3% were KIR 2D (L1, L3, L4, S4 positive on tumor cells, and 74.6% were KIR 2D (L1, L3, L4, S4 positive on TILs. We compared the expression of inhibitory KIR before and after treatment with nivolumab in 11 patients with NSCLC. We found that five (45.5% patients had positive expression of inhibitory KIR in tumor tissue after being treated with anti-PD-1 monoclonal antibodies, two of whom exhibited a significant

  17. Effect of permanent 103Pd radioactive seed implantation on brachytherapy of malignant tumor

    International Nuclear Information System (INIS)

    Chen Ping; Wei Xianzhong; Liu Yanmin; Wu Kaijun; Liang Jianxin; Chen Hanzhang

    2003-01-01

    Objective: To investigate and assess the brachytherapeutic effectiveness of 103 Pd radioactive seeds in malignant tumor therapy. Methods: 196.1-2127.5 MBq 103 Pd seeds were implanted in 21 confirmed malignant tumor patients. The seeds were evenly scattered in 15/21 patients' tumors and peripherally in the remaining 6 cases' tumors. The size and shape, local recurrence and remote metastasis of the tumors were observed. Results: The brachytherapy of 103 Pd seeds in tumor patients resulted in obvious efficacy. No local recurrence and remote metastasis were observed. 19/21 (90.5%) patients scored 0 and 2/21 (9.5%) of them scored 1 in skin acute radiation morbidity scoring criteria within the observation period. Conclusion: The 103 Pd seeds can be safely used in brachytherapy of malignant tumors with lower or medium sensitivity to radiation therapy

  18. Evaluation of Biomarkers Predictive of Benefit from the PD-1 Inhibitor MK-3475 in Patients with Non-Small Cell Lung Cancer and Brain Metastases

    Science.gov (United States)

    2017-07-01

    Small Cell Lung Cancer and Brain Metastases PRINCIPAL INVESTIGATOR: Sarah B. Goldberg, MD CONTRACTING ORGANIZATION: Yale University New Haven, CT...benefit in patients with non- small cell lung cancer (NSCLC). However, the overall response rate is only 20-30% and there is no clearly-defined...9. Appendices……………………………………………………………14 4 1. INTRODUCTION: Lung cancer is the leading cause of cancer death in the United States, resulting in more

  19. [Peritonitis in pediatric patients receiving peritoneal dialysis].

    Science.gov (United States)

    Jellouli, Manel; Ferjani, Meriem; Abidi, Kamel; Hammi, Yosra; Boutiba, Ilhem; Naija, Ouns; Zarrouk, Chokri; Ben Abdallah, Taieb; Gargah, Tahar

    2015-12-01

    Peritonitis on catheter of dialysis represents the most frequent complication of the peritoneal dialysis (PD) in the pediatric population. It remains a significant cause of morbidity and mortality. In this study, we investigated the risk factors for peritonitis in children. In this study, we retrospectively collected the records of 85 patients who were treated with PD within the past ten years in the service of pediatrics of the University Hospital Charles-Nicolle of Tunis. Peritonitis rate was 0.75 episode per patient-year. Notably, peritonitis caused by Gram-positive organisms were more common. Analysis of infection risk revealed three significant independent factors: the poor weight (P=0.0045), the non-automated PD (P=0.02) and the short delay from catheter insertion to starting PD (P=0.02). The early onset peritonitis was significantly associated with frequent peritonitis episodes (P=0.0008). The mean duration between the first and second episode of peritonitis was significantly shorter than between PD commencement and the first episode of peritonitis. We revealed a significant association between Gram-negative peritonitis and the presence of ureterostomy (0.018) and between Gram-positive peritonitis and the presence of exit-site and tunnel infections (0.02). Transition to permanent hemodialysis was needed in many children but no death occurred in patients with peritonitis. Considering the important incidence of peritonitis in our patients, it is imperative to establish a targeted primary prevention. Nutritional care must be provided to children to avoid poor weight. The automated dialysis has to be the modality of choice. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  20. Susceptibility (risk and protective) factors for in-patient violence and self-harm: prospective study of structured professional judgement instruments START and SAPROF, DUNDRUM-3 and DUNDRUM-4 in forensic mental health services.

    LENUS (Irish Health Repository)

    Abidin, Zareena

    2013-01-01

    The START and SAPROF are newly developed fourth generation structured professional judgement instruments assessing strengths and protective factors. The DUNDRUM-3 and DUNDRUM-4 also measure positive factors, programme completion and recovery in forensic settings.

  1. Synthesis of 2-vinylic indoles and derivatives via a Pd-catalyzed tandem coupling reaction.

    Science.gov (United States)

    Fayol, Aude; Fang, Yuan-Qing; Lautens, Mark

    2006-09-14

    A novel one-step synthesis of valuable 2-vinylic indoles and their tricycle derivatives is described. This reaction, which utilizes a gem-dibromovinyl unit as a readily available starting material, occurs via an efficient Pd-catalyzed tandem Buchwald-Hartwig/Heck reaction.

  2. A prospective, observational study comparing the PK/PD relationships of generic Meropenem (Mercide® to the innovator brand in critically ill patients

    Directory of Open Access Journals (Sweden)

    Mer M

    2016-11-01

    Full Text Available Mervyn Mer,1 Jacques Rene Snyman,2 Constance Elizabeth Jansen van Rensburg,2 Jacob John van Tonder,3 Ilze Laurens2 1Department of Medicine, Divisions of Critical Care and Pulmonology, University of the Witwatersrand, Johannesburg, South Africa; 2Office of the Dean, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; 3Scientific Affairs Department, Triclinium Clinical Development (Pty Ltd, Centurion, South Africa Introduction: Clinicians’ skepticism, fueled by evidence of inferiority of some multisource generic antimicrobial products, results in the underutilization of more cost-effective generics, especially in critically ill patients. The aim of this observational study was to demonstrate equivalence between the generic or comparator brand of meropenem (Mercide® and the leading innovator brand (Meronem® by means of an ex vivo technique whereby antimicrobial activity is used to estimate plasma concentration of the active moiety. Methods: Patients from different high care and intensive care units were recruited for observation when prescribed either of the meropenem brands under investigation. Blood samples were collected over 6 hours after a 30 minute infusion of the different brands. Meropenem concentration curves were established against United States Pharmacopeia standard meropenem (Sigma-Aldrich by using standard laboratory techniques for culture of Klebsiella pneumoniae. Patients’ plasma samples were tested ex vivo, using a disc diffusion assay, to confirm antimicrobial activity and estimate plasma concentrations of the two brands. Results: Both brands of meropenem demonstrated similar curves in donor plasma when concentrations in vials were confirmed. Patient-specific serum concentrations were determined from zones of inhibition against a standard laboratory Klebsiella strain ex vivo, confirming at least similar in vivo concentrations as the concentration curves (90% confidence interval overlapped; however

  3. Getting Started with Hibernate 3

    CERN Document Server

    Elliott, James

    2008-01-01

    Hibernate has clearly arrived. Are you ready to benefit from its simple way of working with relational databases as Java objects? This PDF updates the introductory material from the award-winning Hibernate: A Developer's Notebook to teach you how to jump right in and get productive with the current release of Hibernate. You'll be walked through the ins and outs of setting up Hibernate and some related tools that make it easier to use--and that may give you new ideas about how to store information in your Java programs. In short, this PDF gives you exactly the information you need to start u

  4. Starting of nuclear power stations

    International Nuclear Information System (INIS)

    Kotyza, V.

    1988-01-01

    The procedure is briefly characterized of jobs in nuclear power plant start-up and the differences are pointed out from those used in conventional power generation. Pressure tests are described oriented to tightness, tests of the secondary circuit and of the individual nodes and facilities. The possibility is shown of increased efficiency of such jobs on an example of the hydraulic tests of the second unit of the Dukovany nuclear power plant where the second and the third stages were combined in the so-colled integrated hydraulic test. (Z.M.). 5 figs

  5. Getting started With Amazon Redshift

    CERN Document Server

    Bauer, Stefan

    2013-01-01

    Getting Started With Amazon Redshift is a step-by-step, practical guide to the world of Redshift. Learn to load, manage, and query data on Redshift.This book is for CIOs, enterprise architects, developers, and anyone else who needs to get familiar with RedShift. The CIO will gain an understanding of what their technical staff is working on; the technical implementation personnel will get an in-depth view of the technology, and what it will take to implement their own solutions.

  6. Predicting emergency diesel starting performance

    International Nuclear Information System (INIS)

    DeBey, T.M.

    1989-01-01

    The US Department of Energy effort to extend the operational lives of commercial nuclear power plants has examined methods for predicting the performance of specific equipment. This effort focuses on performance prediction as a means for reducing equipment surveillance, maintenance, and outages. Realizing these goals will result in nuclear plants that are more reliable, have lower maintenance costs, and have longer lives. This paper describes a monitoring system that has been developed to predict starting performance in emergency diesels. A prototype system has been built and tested on an engine at Sandia National Laboratories. 2 refs

  7. Fulminant Diabetes in a Patient with Advanced Melanoma on Nivolumab

    Directory of Open Access Journals (Sweden)

    Nora Chokr

    2018-01-01

    Full Text Available Background. Anti-PD-1 agents were approved for advanced melanoma after the landmark trial Checkmate-037. Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells in genetically predisposed people. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy. Case. A 61-year-old male with advanced melanoma presented with a three-day history of nausea, vomiting, and malaise. He was started on nivolumab and ipilimumab. After the third dose, he developed a generalized rash and was prescribed high-dose prednisone. Labs revealed potassium 9.5 mmol/L, sodium 127 mmol/L, bicarbonate 31 mmol, arterial blood pH 7.14, and beta-hydroxybutyrate 13.7 mmol/L. He was diagnosed with diabetic ketoacidosis. Hemoglobin A1C was 6.9%. C-peptide was undetectable (<0.1 ng/ml. Glutamic acid decarboxylase autoantibodies, zinc transporter 8 autoantibodies, insulin autoantibodies, islet antigen 2 autoantibodies, and islet cell antibodies were all negative. Conclusion. Anti-PD-1 immunotherapy is effective in cancers refractory to standard chemotherapy. These agents can precipitate autoimmune disorders. As the use of anti-PD-1 agents is expected to rise, physicians should be educated about the potential side effects. We recommend conducting routine blood glucose checks in patients on these agents.

  8. Effect of assistance on peritonitis risk in diabetic patients treated by peritoneal dialysis: report from the French Language Peritoneal Dialysis Registry.

    Science.gov (United States)

    Benabed, Anais; Bechade, Clemence; Ficheux, Maxence; Verger, Christian; Lobbedez, Thierry

    2016-04-01

    Diabetic patients treated by peritoneal dialysis (PD) have been reported to be at an increased risk of peritonitis. This has been attributed to impairment in host defense, visual impairment, disability and muscle wasting, which could compromise ability to safely perform catheter connections. This study aimed to evaluate whether assisted PD is associated with a lower risk of peritonitis in diabetic patients. This was a retrospective study based on data from the French Language Peritoneal Dialysis Registry. We included diabetic patients starting PD between 1 January 2002 and 31 December 2012. The end of the observation period was 31 December 2013. Using complementary regression analysis (Fine and Gray, Hurdle models), we assessed the relationship between peritonitis occurrence, peritonitis number over time and the type of assisted PD. Of the 3598 diabetic patients, there were 2040 patients on nurse-assisted PD. These patients were older, more comorbid and more frequently on continuous ambulatory peritoneal dialysis (CAPD). In the multivariate analysis, nurse assistance was associated with a reduced risk of peritonitis in the Fine and Gray [subdistribution hazard ratio: 0.78 (95% confidence interval, CI, 0.68-0.89)] and in the first component of the Hurdle models [rate ratio: 0.82 (95% CI 0.71-0.93)], but not a lower incidence of peritonitis after an initial episode [rate ratio: 0.82 (95% CI 0.95-1.38)]. Transplant failure, glomerulonephritis and CAPD were associated with an increased risk. In France, nurse-assisted PD is associated with a lower risk of peritonitis in diabetic patients treated by PD but not a lower incidence of peritonitis. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  9. G6PD: The Test

    Science.gov (United States)

    ... a G6PD deficiency if a male inherits the single X chromosome with an altered gene. Since women have two X sex chromosomes, they inherit two ... deficiency. In addition, a mother may pass the single mutated gene to any male children. Rarely do women have two mutated gene copies ( homozygous ), which could ...

  10. Starting a nursing consultation practice.

    Science.gov (United States)

    Schulmeister, L

    1999-03-01

    Because the clinical nurse specialist (CNS) role has been changed or eliminated in many hospital organizations, many CNSs in career transition are considering establishing collaborative or independent nursing consultation practices. Opportunities for consultants exist in diverse practice settings and specialties. Before starting a consultation practice, the CNS should carefully examine goals, identify resources, and begin contacting potential referral sources. He or she must also decide what form of business organization to establish and write a business plan to solidify ideas and prepare for the unexpected. Most CNS consultants rely on personal savings to cover initial business and personal expenses, and many continue working as a CNS until the consultation practice is established. Fees can be set based on community standards, what the market will bear, desired projected income, or a third-party payor's fee schedule. The consultation practice can be marketed by word of mouth, inexpensive advertising techniques such as distributing flyers and business cards, direct mall, and media advertising. In today's healthcare marketplace, opportunities abound for the CNS risk-taker interested in starting a nursing consultation practice.

  11. The start of the harvest

    CERN Multimedia

    2011-01-01

    The first major particle physics summer conference has just started this week in Grenoble. After the Quark-Matter conference, the Europhysics Conference on High-Energy Physics marks the start of a promising harvest for the LHC experiments.   For the first time, the collaborations will be presenting their latest results based on all luminosity taken until end of June, which will provide more precise measurements in many areas. Thanks to the excellent performance of the LHC, the experiments have already accumulated a substantial quantity of data allowing them to push back the known limits and refine measurements in many fields ranging from b physics to the search for the Higgs boson and for dark matter. At the time of writing, the LHC collaborations are about to present these new results in an energy range which has never previously been explored. I have congratulated all the teams involved in getting the LHC into operation in record time with great efficiency. Today I would like to acknowledge the...

  12. Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A.

    Science.gov (United States)

    Cho, Hyosun; Kang, Hyojeung; Kim, Chang Wook; Kim, Hee Yeon; Jang, Jeong Won; Yoon, Seung Kew; Lee, Chang Don

    2016-03-01

    The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.

  13. Electron Bernstein wave current drive in the start-up phase of a tokamak discharge

    International Nuclear Information System (INIS)

    Montes, A.; Ludwig, G.O.

    1986-04-01

    Current drive by electron Bernstein waves in the start-up phase of tokamak discharges is studied. A general analytical expression is derived for the figure of merit J/Pd associated with these waves. This is coupled with a ray tracing code, allowing the calculation of the total current generated per unit of incident power in realistic tokamak conditions. The resuts show that the electron Bernstein waves can drive substantial currents even at very low electron temperatures. (Author) [pt

  14. PD-L1-specific T cells

    DEFF Research Database (Denmark)

    Ahmad, Shamaila Munir; Borch, Troels Holz; Hansen, Morten

    2016-01-01

    -specific T cells that recognize both PD-L1-expressing immune cells and malignant cells. Thus, PD-L1-specific T cells have the ability to modulate adaptive immune reactions by reacting to regulatory cells. Thus, utilization of PD-L1-derived T cell epitopes may represent an attractive vaccination strategy...... for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses...

  15. Facial Emotion Recognition Impairment in Patients with Parkinson's Disease and Isolated Apathy

    Directory of Open Access Journals (Sweden)

    Mercè Martínez-Corral

    2010-01-01

    Full Text Available Apathy is a frequent feature of Parkinson's disease (PD, usually related with executive dysfunction. However, in a subgroup of PD patients apathy may represent the only or predominant neuropsychiatric feature. To understand the mechanisms underlying apathy in PD, we investigated emotional processing in PD patients with and without apathy and in healthy controls (HC, assessed by a facial emotion recognition task (FERT. We excluded PD patients with cognitive impairment, depression, other affective disturbances and previous surgery for PD. PD patients with apathy scored significantly worse in the FERT, performing worse in fear, anger, and sadness recognition. No differences, however, were found between nonapathetic PD patients and HC. These findings suggest the existence of a disruption of emotional-affective processing in cognitive preserved PD patients with apathy. To identify specific dysfunction of limbic structures in PD, patients with isolated apathy may have therapeutic and prognostic implications.

  16. Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

    OpenAIRE

    Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

    2015-01-01

    Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L...

  17. Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types

    Science.gov (United States)

    Scognamiglio, Giosuè; De Chiara, Anna; Di Bonito, Maurizio; Tatangelo, Fabiana; Losito, Nunzia Simona; Anniciello, Annamaria; De Cecio, Rossella; D’Alterio, Crescenzo; Scala, Stefania; Cantile, Monica; Botti, Gerardo

    2016-01-01

    In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. PMID:27213372

  18. Limb/trunk lean mass ratio as a risk factor for mortality in peritoneal dialysis patients

    Directory of Open Access Journals (Sweden)

    Seok Hui Kang

    2012-06-01

    Full Text Available Protein energy wasting (PEW is a common problem in dialysis patients. There have been few reports on the effects of regional lean mass distribution for peritoneal dialysis (PD patients. We reviewed the medical records and identified all adults who received PD between May 2001 and May 2011. Five hundred thirty four patients were enrolled. The clinical and laboratory data were collected at 1 and 12 months. Regional lean masses were measured by dual-energy X-ray absorptiometry. The limb/trunk lean mass ratio (LTLM was defined as a value on dividing the sum of four limbs by the trunk lean mass. The mean age at the start of PD was 53.2±14.1 years. Diabetes mellitus (DM was most common underlying disease of end-stage renal disease (49.6%. In males, the low LTLM tertile was associated with low body mass index, creatinine, arm muscle circumference, and high C-reactive protein. In females, the low LTLM tertile was associated with low creatinine and normalized protein equivalent of nitrogen appearance. On both univariate and multivariate analysis adjusted for age, Davies risk index, and residual renal function, initial low LTLM tertile and maintenance of low LTLM were associated with mortality in PD patients. Distribution or change of regional lean mass may be more useful for predicting nutritional status. Initial low LTLM and maintenance of low LTLM were associated with mortality in PD patients. LTLM as a new marker would be useful for predicting the nutritional status and the mortality in patients on PD.

  19. The patients’ perspective: Results of a survey assessing knowledge about and attitudes toward depression in PD

    Directory of Open Access Journals (Sweden)

    Irene Hegeman Richard

    2007-01-01

    Full Text Available Irene Hegeman Richard1, Kori A LaDonna1, Rosanne Hartman2, Carol Podgorski1, Roger Kurlan1, SAD-PD Study Group31University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; 2Canisius College, Buffalo, NY, USA; 3Please see Appendix for members of the SAD-PD Study GroupAbstract: We report results of a survey assessing patients’ knowledge about and attitudes towards depression in Parkinson’s disease (PD. 345 patients from 8 tertiary care centers responded (43% response rate. Overall, patients were relatively knowledgeable about depression and its occurrence in PD. However, many patients believed that depression is a normal reaction to the illness. While many respondents would be reluctant to initiate a discussion of depression during a clinical evaluation, most would feel comfortable talking about depression with their physician if he or she asked them questions about their mood. Based on the results of this survey, we recommend the following approach for physicians: (1 inform PD patients that, although a frequent occurrence, depression need not be accepted as a “normal reaction” to PD; and (2 routinely inquire about depressive symptoms rather than waiting for the patient to spontaneously report them.Keywords: depression, Parkinson’s disease, survey

  20. A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma.

    Science.gov (United States)

    Sakane, Tadashi; Murase, Takayuki; Okuda, Katsuhiro; Takino, Hisashi; Masaki, Ayako; Oda, Risa; Watanabe, Takuya; Kawano, Osamu; Haneda, Hiroshi; Moriyama, Satoru; Saito, Yushi; Yamada, Takeshi; Nakanishi, Ryoichi; Inagaki, Hiroshi

    2018-01-23

    Currently, four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays. The cases of 53 patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays showed similar scores in each case. Histopathologically, high TC scores were observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no significant relationships among the IC scores in the four assays. In SqCCs, the high expression of PD-L1 (defined as ≥50% TC score) in TCs tended to be associated with early stage cancer. The patients with high expression levels of PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In thymic carcinomas, the staining pattern showed high concordance among the four assays when TCs - rather than ICs - were stained. High PD-L1 positivity in TCs, especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a promising therapeutic approach.

  1. 30 CFR 75.1913 - Starting aids.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with recommendations provided by the starting aid...

  2. Parental discussion of G6PD deficiency and child health: implications for clinical practice.

    Science.gov (United States)

    Guan, Yue; Roter, Debra L; Huang, Aichu; Erby, Lori A H; Chien, Yin-Hsiu; Hwu, Wuh-Liang

    2014-03-01

    Parents are encouraged to discuss self-care with children affected by G6PD deficiency; however, little is known about the extent or impact of these discussions on the physical and psychosocial health of these children. The purpose of this study was to examine the nature of parental-child discussions of G6PD deficiency self-care and their relationship to child health. A quantitative cross-sectional survey of 178 Taiwanese parents of children with G6PD deficiency was conducted. The extent of parental-child self-care discussions was assessed in regards to coverage of nine key topics. Parent's G6PD deficiency status, knowledge of haemolytic anaemia symptoms and reported G6PD deficiency education from providers were examined as correlates of parental discussion. Child health was assessed with the child health questionnaire-parent form (Chinese version) and a 13-item haemolytic anaemia symptom list. Self-care discussions were positively correlated with parental G6PD deficiency status (β=2.08, p=0.03), accurate identification of haemolytic anaemia symptoms (β=0.18, p=0.01), the thoroughness and clarity of patient education (β=0.14, pchild age (β=1.04, pchild health (β=1.18, pchild G6PD deficiency self-care discussions are associated with better child health, and parental involvement in these discussions is facilitated by the thoroughness and clarity of patient education received from providers.

  3. 103PD brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma

    International Nuclear Information System (INIS)

    Dattoli, Michael; Wallner, Kent; Sorace, Richard; Koval, John; Cash, Jennifer; Acosta, Rudolph; Brown, Charles; Etheridge, James; Binder, Michael; Brunelle, Richard; Kirwan, Novelle; Sanchez, Servando; Stein, Douglas; Wasserman, Stuart

    1996-01-01

    Purpose: To summarize biochemical failure rates and morbidity of external beam irradiation (EBRT) combined with palladium ( 103 Pd) boost for clinically localized high-risk prostate carcinoma. Methods and Materials: Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) >15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103 Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal 103 Pd brachytherapy for clinically localized, high-risk prostate cancer compare favorably with that reported after conventional dose EBRT alone. Morbidity has been acceptable

  4. Transfer of allogeneic CD4+ T cells rescues CD8+ T cells in anti-PD-L1–resistant tumors leading to tumor eradication

    Science.gov (United States)

    Arina, Ainhoa; Karrison, Theodore; Galka, Eva; Schreiber, Karin; Weichselbaum, Ralph R.; Schreiber, Hans

    2017-01-01

    Adoptively transferred CD8+ T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell–mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule Kb needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8+ T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months. Escape was associated with reduced numbers of circulating 2C cells. Tumor-infiltrating 2C cells produced significantly less TNFα and expressed more of the “exhaustion” markers PD-1 and Tim-3 than T cells from lymphoid organs. High-dose local ionizing radiation, depletion of myeloid-derived suppressor cells, infusions of additional 2C cells, and antibodies blocking PD-L1 did not prevent tumor escape. In contrast, adoptive transfer of allogeneic CD4+ T cells restored the numbers of circulating Ag-specific CD8+ T cells and their intratumoral function, resulting in tumor eradication. These CD4+ T cells had no antitumor effects in the absence of CD8+ T cells and recognized the alloantigen cross-presented on tumor stroma. CD4+ T cells might also be effective in cancer patients when PD1/PD-L1 blockade does not rescue intratumoral CD8+ T-cell function and tumors persist. PMID:28077434

  5. A Regional PD Strategy for EPR Systems: Evidence-Based IT Development

    DEFF Research Database (Denmark)

    Simonsen, Jesper; Hertzum, Morten

    2006-01-01

    One of the five regions in Denmark has initiated a remark-able and alternative strategy for the development of Elec-tronic Patient Record (EPR) systems. This strategy is driven by Participatory Design (PD) experiments and based on evidence of positive effects on the clinical practice when using EPR...... systems. We present this PD strategy and our related research on evidence-based IT development. We report from a newly completed PD experiment with EPR in the region conducted through a close collaboration compris-ing a neurological stroke unit, the region’s EPR unit, the vendor, as well as the authors....

  6. START: an advanced radiation therapy information system.

    Science.gov (United States)

    Cocco, A; Valentini, V; Balducci, M; Mantello, G

    1996-01-01

    START is an advanced radiation therapy information system (RTIS) which connects direct information technology present in the devices with indirect information technology for clinical, administrative, information management integrated with the hospital information system (HIS). The following objectives are pursued: to support decision making in treatment planning and functional and information integration with the rest of the hospital; to enhance organizational efficiency of a Radiation Therapy Department; to facilitate the statistical evaluation of clinical data and managerial performance assessment; to ensure the safety and confidentiality of used data. For its development a working method based on the involvement of all operators of the Radiation Therapy Department, was applied. Its introduction in the work activity was gradual, trying to reuse and integrate the existing information applications. The START information flow identifies four major phases: admission, visit of admission, planning, therapy. The system main functionalities available to the radiotherapist are: clinical history/medical report linking function; folder function; planning function; tracking function; electronic mail and banner function; statistical function; management function. Functions available to the radiotherapy technician are: the room daily list function; management function: to the nurse the following functions are available: patient directing function; management function. START is a departmental client (pc-windows)-server (unix) developed on an integrated database of all information of interest (clinical, organizational and administrative) coherent with the standard and with a modular architecture which can evolve with additional functionalities in subsequent times. For a more thorough evaluation of its impact on the daily activity of a radiation therapy facility, a prolonged clinical validation is in progress.

  7. Assessment of striatal & postural deformities in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2016-01-01

    Interpretation & conclusions: Our results showed that striatal and postural deformities were common and present in about half of the patients with PD. These deformities we more common in patients with advanced stage of PD.

  8. Starting up the Saturne synchrotron

    International Nuclear Information System (INIS)

    Salvat, M.

    1958-02-01

    Illustrated by many drawings and graphs, this report describes and comments all operations and measurements to be performed for starting up the Saturne synchrotron until particle acceleration exclusively. The author reports the study of beam as it goes out of the Van de Graaff: experiment of position and stability of the beam axis, study of beam current and geometric characteristics (calibration of the induction probe), experiment of mass separation and proton percentage, and adjustment of regulation and Van de Graaff fall law. In a second part, he reports the optics alignment and the study of optics property (installation of the different sectors, study of inflector end voltage, and influence of inflector position in the chamber). The third part addresses the examination of phenomena associated with injection: injection method and definition of the initial instant, search for injection optimum conditions, study of particle lifetime and of phenomena on the inner probe. The fourth part proposes theoretical additional elements regarding the movement of particles at the injection in the useful area, and phenomena occurring on targets and on the inner probe

  9. Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA

    Directory of Open Access Journals (Sweden)

    Mayela Rodríguez-Violante

    2014-01-01

    Full Text Available Introduction. Neuropsychiatric symptoms in Parkinson’s disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s disease (SEND-PD has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA. Methods. Patients with Parkinson’s disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison. Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was 2.9±3.1 (range from 0 to 16. The neuropsychiatric MDS-UPDRS part IA score was 2.9±3 (range from 0 to 14. The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes was rs=0.93 (all, P<0.001. Conclusion. A high association between equivalent items of the SEND-PD and the MDS-UPDRS was found.

  10. Prognostic Value of PD-L1 in Breast Cancer: A Meta-Analysis.

    Science.gov (United States)

    Wang, Changjun; Zhu, Hanjiang; Zhou, Yidong; Mao, Feng; Lin, Yan; Pan, Bo; Zhang, Xiaohui; Xu, Qianqian; Huang, Xin; Sun, Qiang

    2017-07-01

    Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD-L1 overexpression was found in 25.8% of breast cancer patients. PD-L1 (+) associated with several high-risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2-rich and Basal-like p = 0.000). PD-L1 overexpression had no significant impact on metastasis-free survival (HR 0.924, 95% CI = 0.747-1.141, p = 0.462), disease-free survival (HR 1.122, 95% CI = 0.878-1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640-1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010-2.451, p = 0.045). PD-L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD-L1 assessment assay and well-controlled clinical trials are warranted to clarify its prognostic and therapeutic value. © 2017 Wiley Periodicals, Inc.

  11. Danish Ophthalmology - from start to 1865.

    Science.gov (United States)

    Norn, Mogens

    2016-03-01

    This short paper mentioned the medical treatment using the 'holy' springs, the first 'eye doctor' in Denmark, the first picture of spectacles which was found in Viborg Cathedral of the high priest before he performs circumcisio praeputii on Jesus Christ, further cataract reclination in Denmark from around year zero and cataract extraction in 1667 in Denmark on a goose by Francisco Borri and on humans by the Danish Georg Heuermann in 1755. Epidemic military eye diseases in 1807, 1856 and 1865 are also described in this study. From 1856, a new ophthalmological period started in Denmark with the first eye hospital (lazaret only for eye diseases), and in 1864, patients with eye diseases were transported from the few beds in the surgical departments in the municipal hospital to the first civil eye department in Denmark, the eye hospital Sct. Annae in Copenhagen. The new scientific period started with Jacob Christian Bentz (ophthalmia granulosa, joint editor of the Danish Medical Journal) and Heinrich Lehmann. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  12. Application of STOPP and START criteria: interrater reliability among pharmacists.

    LENUS (Irish Health Repository)

    Ryan, Cristin

    2009-07-01

    Inappropriate prescribing is a well-documented problem in older people. The new screening tools, STOPP (Screening Tool of Older Peoples\\' Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) have been formulated to identify potentially inappropriate medications (PIMs) and potential errors of omissions (PEOs) in older patients. Consistent, reliable application of STOPP and START is essential for the screening tools to be used effectively by pharmacists.

  13. [How to start a neuroimaging study].

    Science.gov (United States)

    Narumoto, Jin

    2012-06-01

    In order to help researchers understand how to start a neuroimaging study, several tips are described in this paper. These include 1) Choice of an imaging modality, 2) Statistical method, and 3) Interpretation of the results. 1) There are several imaging modalities available in clinical research. Advantages and disadvantages of each modality are described. 2) Statistical Parametric Mapping, which is the most common statistical software for neuroimaging analysis, is described in terms of parameter setting in normalization and level of significance. 3) In the discussion section, the region which shows a significant difference between patients and normal controls should be discussed in relation to the neurophysiology of the disease, making reference to previous reports from neuroimaging studies in normal controls, lesion studies and animal studies. A typical pattern of discussion is described.

  14. Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy.

    Science.gov (United States)

    Zhu, Bo; Tang, Liming; Chen, Shuyang; Yin, Chengqian; Peng, Shiguang; Li, Xin; Liu, Tongzheng; Liu, Wei; Han, Changpeng; Stawski, Lukasz; Xu, Zhi-Xiang; Zhou, Guangbiao; Chen, Xiang; Gao, Xiumei; Goding, Colin R; Xu, Nan; Cui, Rutao; Cao, Peng

    2018-05-22

    Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2). Depletion of NRF2 significantly induces tumor infiltration by both CD8 + and CD4 + T cells to suppress melanoma progression, and combining NRF2 inhibition with anti-PD-1 treatment enhanced its anti-tumor function. Our studies identify a critical and targetable PD-L1 upstream regulator and provide an alternative strategy to inhibit the PD-1/PD-L1 signaling in melanoma treatment.

  15. Pain Correlates with Sleep Disturbances in Parkinson's Disease Patients.

    Science.gov (United States)

    Fu, Yun-Ting; Mao, Cheng-Jie; Ma, Li-Jing; Zhang, Hui-Jun; Wang, Yi; Li, Jie; Huang, Jun-Ying; Liu, Jun-Yi; Liu, Chun-Feng

    2018-01-01

    Both sleep disorders and pain decrease quality of life in patients with Parkinson's disease (PD). However, little is known about the relationship between objective sleep disturbances and pain in patients with PD. This study aimed to (1) examine the clinical characteristics of pain in PD patients and (2) explore the correlation between pain and sleep disturbances in PD patients. Parkinson's disease patients (N = 144) underwent extensive clinical evaluations of motor and nonmotor symptoms and characteristics of pain. Overnight video-polysomnography was also conducted. Clinical characteristics and sleep parameters were compared between PD patients with or without pain. Pain was reported by 75 patients (52.1%), with 49 (65.3%) reporting pain of at least moderate severity. PD patients with pain were older and had longer disease duration, more severe PD symptoms as assessed by Hoehn and Yahr stage and the Unified Parkinson's Disease Rating Scale, and higher L-dopa equivalent daily dose compared with PD patients without pain. PD patients with pain also showed significantly decreased sleep efficiency (57.06% ± 15.84% vs. 73.80% ± 12.00%, P daily living, depressed mood, higher percentage of N1 sleep, and lower sleep efficiency were independent predictors of pain in patients with PD. Musculoskeletal pain is the most common type of pain in patients with PD. Disrupted sleep continuity, altered sleep architecture, depressed mood, and compromised activities of daily living may be associated with pain in patients with PD. © 2017 World Institute of Pain.

  16. PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules.

    Science.gov (United States)

    Geng, Qiaohong; Jiao, Peifu; Jin, Peng; Su, Gaoxing; Dong, Jinlong; Yan, Bing

    2018-02-12

    The recent regulatory approvals of immune checkpoint protein inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them with unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types. Besides monoclonal antibodies, diverse PD- 1/PD-L1 inhibiting candidates, such as peptides, small molecules have formed a powerful collection of weapons to fight cancer. The goal of this review is to summarize and discuss the current PD-1/PD-L1 inhibitors including candidates under clinical development, their molecular interactions with PD-1 or PD-L1, the disclosed structureactivity relationships of peptides and small molecules as inhibitors. Current PD-1/PD-L1 inhibitors under clinical development are exclusively dominated by antibodies. The molecular interactions of therapeutic antibodies with PD-1 or PD-L1 have been gradually elucidated for the design of novel inhibitors. Various peptides and traditional small molecules have been investigated in preclinical model to discover novel PD-1/PD-L1 inhibitors. Peptides and small molecules may play an important role in immuno-oncology because they may bind to multiple immune checkpoint proteins via rational design, opening opportunity for a new generation of novel PD-1/PD-L1 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. AB073. Classic infantile-onset Pompe disease: phenotypes and outcomes of 5 Vietnamese patients receiving enzyme replacement therapy

    Science.gov (United States)

    Nguyen, Khanh Ngoc; Do, Mai Thi Thanh; Can, Ngoc Thi Bich; Hwu, Wuh-Liang; Vu, Dung Chi

    2017-01-01

    Background Pompe disease (PD) or glycogen storage disease type II is a lysosomal storage disorder, caused by mutations of GAA gene which results in deficiency of acid alpha-glucosidase (GAA) enzyme that involves in metabolism of glycogen in the lysosomes. Its incidence is 1/14,000–1/100,000. PD is divided into three types: classic infantile onset, non-classic infantile onset, and late onset. Early enzyme replacement therapy (ERT) before developing respiratory distress may lead to good outcome. Since 2013, we have identified 16 cases with classic infantile-onset and 5 cases were treated with ERT. Herein, we describe phenotypes and outcomes of five infantile-onset PD patients who received ERT. Methods GAA enzyme assay was done at National Taiwan University Hospital. Results Ages of diagnosis were 12, 38 and 70 days, 5 and 9 months of age. Clinical presentations included macroglossia (5/5), hypertrophic cardiomyopathy (5/5), failure to thrive (5/5), facial weakness and hypotonia (3 patients diagnosed after 70 days of age), respiratory failure (1 patient diagnosed at 9 months of age). All patients had mildly elevated plasma CK (270–380 UI/L) and transaminase (60–260 UI/l). Ages at starting ERT were 28 and 58 days, 3, 6 and 10 months. The time intervals from diagnosis to starting ERT were between 14 days and 1 month. The durations of ERT were 4–22 months. The outcomes were good. All patients had improvement of cardiac functions shown on echocardiography, respiratory status, and motor development. The patient who first received ERT at 10 months of age was reportedly dead at home due to food obstruction at 18 months of age. Current ages of the survivors were 5–24 months. Conclusions Patients with classic infantile-onset PD will have good outcomes if ERT is started early. Newborn screening for this disease is necessary to yield an early diagnosis.

  18. PD-1 and PD-L1 inhibitors after platinum-based chemotherapy or in first-line therapy in cisplatin-ineligible patients: Dramatic improvement of prognosis and overall survival after decades of hopelessness in patients with metastatic urothelial cancer.

    Science.gov (United States)

    Resch, Irene; Shariat, Shahrokh F; Gust, Kilian M

    2018-01-01

    Until recently, there were no true innovations in the management of locally advanced (aUC) and metastatic urothelial cancer (mUC) in the last three decades. Vinflunine has been approved by the EMA (European Medicines Agency) with only limited improvement compared to best supportive care in second line treatment. In addition, gemcitabine/cisplatin has been established as an alternative to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The advent of checkpoint inhibitors (CPI) revolutionized the care of these patients, transforming a unanimously deadly disease into one with hope through sustained disease control. Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. All five CPI are FDA-approved as second-line therapy with atezolizumab and pembrolizumab also being approved for first-line therapy in cisplatin-ineligible patients. The rapid acceptance in the treatment algorithm of UC is based on the impressive clinical efficacy of these agents in some patients, combined with their excellent safety profile. These new agents are indeed the most important advancement in UC care. However, the challenge in the age of precision medicine is to identify the patients who are most likely to benefit from CPIs, as the majority of patients do not respond to CPI. Toward this goal, validation of clinical, molecular and imaging biomarkers that serve for prediction and monitoring of treatment response are of central necessity.

  19. Preschool Facilities - MDC_HeadStart

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A label (point) feature class of Head Start / Early Head Start/ Delegate Agencies/ Child Care Partnership & Family Day Care Homes Programs location in Miami-Dade...

  20. Drug Abuse Prevention Starts with Parents

    Science.gov (United States)

    ... Stages Listen Español Text Size Email Print Share Drug Abuse Prevention Starts with Parents Page Content Article Body ... for a time when drugs may be offered. Drug abuse prevention starts with parents learning how to talk ...

  1. MIS gas sensors based on porous silicon with Pd and WO{sub 3}/Pd electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Solntsev, V.S. [Institute of Semiconductor Physics, National Academy of Science of Ukraine, 03028, Kiev (Ukraine); Gorbanyuk, T.I., E-mail: tatyanagor@mail.r [Institute of Semiconductor Physics, National Academy of Science of Ukraine, 03028, Kiev (Ukraine); Litovchenko, V.G.; Evtukh, A.A. [Institute of Semiconductor Physics, National Academy of Science of Ukraine, 03028, Kiev (Ukraine)

    2009-09-30

    Pd and WO{sub 3}/Pd gate metal-oxide-semiconductor (MIS) gas sensitive structures based on porous silicon layers are studied by the high frequency C(V) method. The chemical compositions of composite WO{sub 3}/Pd electrodes are characterized by secondary-ion mass spectrometry (SIMS). The atomic force microscopy (AFM) was used for morphologic studies of WO{sub 3}/Pd films. As shown in the experiments, WO{sub 3}/Pd structures are more sensitive and selective to the adsorption of hydrogen sulphide compared to Pd gate. The analyses of kinetic characteristics allow us to determine the response and characteristic times for these structures. The response time of MIS-structures with thin composite WO{sub 3}/Pd electrodes (the thickness of Pd is about 50 nm with WO{sub 3} clusters on its surface) is slower compared to the structures with Pd electrodes. Slower sensor responses of WO{sub 3}-based gas sensors may be associated with different mechanism of gas sensitivity of given structures. The enhanced sensitivity and selectivity to H{sub 2}S action of WO{sub 3}/Pd MIS-structures can also be explained by the chemical reaction that occurs at the catalytic active surface of gate electrodes. The possible mechanisms of enhanced sensitivity and selectivity to H{sub 2}S adsorption of MIS gas sensors with WO{sub 3}/Pd composite gate electrodes compared to pure Pd have been analyzed.

  2. Investigating unexpected magnetism of mesoporous silica-supported Pd and PdO nanoparticles

    KAUST Repository

    Song, Hyon Min; Zink, Jeffrey I.; Khashab, Niveen M.

    2015-01-01

    supported Pd and PdO NPs. The heating rate and the annealing conditions determine the particle size and the phase of the NPs, with a fast heating rate of 30 °C/min producing the largest supported Pd NPs. Unusual magnetic behaviors are observed. (1) Contrary

  3. Imbalance of Circulating Monocyte Subsets and PD-1 Dysregulation in Q Fever Endocarditis: The Role of IL-10 in PD-1 Modulation

    Science.gov (United States)

    Ka, Mignane B.; Gondois-Rey, Françoise; Capo, Christian; Textoris, Julien; Million, Mathieu; Raoult, Didier; Olive, Daniel; Mege, Jean-Louis

    2014-01-01

    Q fever endocarditis, a severe complication of Q fever, is associated with a defective immune response, the mechanisms of which are poorly understood. We hypothesized that Q fever immune deficiency is related to altered distribution and activation of circulating monocyte subsets. Monocyte subsets were analyzed by flow cytometry in peripheral blood mononuclear cells from patients with Q fever endocarditis and controls. The proportion of classical monocytes (CD14+CD16− monocytes) was similar in patients and controls. In contrast, the patients with Q fever endocarditis exhibited a decrease in the non-classical and intermediate subsets of monocytes (CD16+ monocytes). The altered distribution of monocyte subsets in Q fever endocarditis was associated with changes in their activation profile. Indeed, the expression of HLA-DR, a canonical activation molecule, and PD-1, a co-inhibitory molecule, was increased in intermediate monocytes. This profile was not restricted to CD16+ monocytes because CD4+ T cells also overexpressed PD-1. The mechanism leading to the overexpression of PD-1 did not require the LPS from C. burnetii but involved interleukin-10, an immunosuppressive cytokine. Indeed, the incubation of control monocytes with interleukin-10 led to a higher expression of PD-1 and neutralizing interleukin-10 prevented C. burnetii-stimulated PD-1 expression. Taken together, these results show that the immune suppression of Q fever endocarditis involves a cross-talk between monocytes and CD4+ T cells expressing PD-1. The expression of PD-1 may be useful to assess chronic immune alterations in Q fever endocarditis. PMID:25211350

  4. PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

    Science.gov (United States)

    Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

    2016-09-13

    Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.

  5. What Happens at the Lesson Start?

    Science.gov (United States)

    Saloviita, Timo

    2016-01-01

    Transitional periods, such as lesson starts, are necessary steps from one activity to another, but they also compete with time for actual learning. The aim of the present study was to replicate a previous pilot study on lesson starts and explore possible disturbances. In total, 130 lesson starts in Finnish basic education in grades 1-9 were…

  6. Health Coordination Manual. Head Start Health Services.

    Science.gov (United States)

    Administration for Children, Youth, and Families (DHHS), Washington, DC. Head Start Bureau.

    Part 1 of this manual on coordinating health care services for Head Start children provides an overview of what Head Start health staff should do to meet the medical, mental health, nutritional, and/or dental needs of Head Start children, staff, and family members. Offering examples, lists, action steps, and charts for clarification, part 2…

  7. Teaching iSTART to Understand Spanish

    Science.gov (United States)

    Dascalu, Mihai; Jacovina, Matthew E.; Soto, Christian M.; Allen, Laura K.; Dai, Jianmin; Guerrero, Tricia A.; McNamara, Danielle S.

    2017-01-01

    iSTART is a web-based reading comprehension tutor. A recent translation of iSTART from English to Spanish has made the system available to a new audience. In this paper, we outline several challenges that arose during the development process, specifically focusing on the algorithms that drive the feedback. Several iSTART activities encourage…

  8. Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function.

    Directory of Open Access Journals (Sweden)

    Maria Sophia Mackroth

    2016-11-01

    Full Text Available In acute Plasmodium falciparum (P. falciparum malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections.

  9. Controlling the size and morphology of Au@Pd core-shell nanocrystals by manipulating the kinetics of seeded growth.

    Science.gov (United States)

    Li, Jing; Zheng, Yiqun; Zeng, Jie; Xia, Younan

    2012-06-25

    This article reports a systematic study of the seed-mediated growth of Au@Pd core-shell nanocrystals with a variety of controlled sizes and morphologies. The key to the success of this synthesis is to manipulate the reaction kinetics by tuning a set of reaction parameters, including the type and concentration of capping agent, the amount of ascorbic acid used as the reducing agent, and the injection rate used for the precursor solution. Starting from Au nanospheres of 11 nm in diameter as the seeds, Au@Pd core-shell nanocrystals with a number of morphologies, including octahedra, concave octahedra, rectangular bars, cubes, concave cubes, and dendrites, could all be obtained by simply altering the reaction rate. For the first time, it was possible to generate Au@Pd nanocrystals with concave structures on the surfaces while their sizes were kept below 20 nm. In addition, the as-prepared Au@Pd nanocubes can be used as seeds to generate Au@Pd@Au and Au@Pd@Au@Pd nanocrystals with multishelled structures. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2

    NARCIS (Netherlands)

    Zak, Krzysztof M.; Grudnik, Przemyslaw; Magiera, Katarzyna; Dömling, Alexander; Dubin, Grzegorz; Holak, Tad A.

    2017-01-01

    Cancer cells can avoid and suppress immune responses through activation of inhibitory immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4. Blocking the activities of these proteins with monoclonal antibodies, and thus restoring T cell function, has delivered breakthrough therapies against

  11. Frequency of G6PD Mediterranean in individuals with and without malaria in Southern Pakistan.

    Science.gov (United States)

    Moiz, Bushra; Arshad, Haroon Muhammad; Raheem, Ahmed; Hayat, Hasan; Karim Ghanchi, Najia; Beg, M Asim

    2017-10-24

    Pakistan has an estimated annual burden of 1.5 million malaria cases. The current situation calls for an effective malaria control and eradication programme in this country. Currently, primaquine is an attractive option for eliminating reservoirs of Plasmodium vivax hypnozoites and killing gametocytes of Plasmodium falciparum. However, this drug causes haemolysis in individuals who are glucose-6-phosphate (G6PD) deficient. It is important to map G6PD deficiency and malaria distribution in Pakistan to design an effective malaria eradication regimen. Frequency of G6PD deficiency (G6PDd) in malaria patients has not been reported from Pakistan in any meaningful way. The purpose of this study was to evaluate the frequency of G6PD c.563C>T (G6PD Mediterranean) in male individuals with and without falciparum malaria. Two hundred and ten archived DNA samples from males (110 from falciparum malaria patients and 100 from healthy individuals) were utilized in this study. Healthy blood donors were selected based on stringent pre-defined criteria. Patients were confirmed for malaria parasites on microscopy and or immune chromatographic assay detecting P. falciparum histidine-rich protein 2. Parasitaemia was also computed. DNA samples were tested for G6PD c.563C>T mutation through PCR-RFLP according to the previously defined protocol and its allelic frequency was computed. G6PD c.563C>T was observed in four of 110 patients with falciparum malaria and in two of 100 healthy donors. Mean (± SD) haemoglobin, median (IQR) platelet and median (IQR) parasite count in G6PD-deficient malaria-patients were 8.9 ± 0.9 g/dL, 124 × 109/L (IQR 32, 171) and 57,920/μL of blood (IQR 12,920, 540,000) respectively. Cumulative allelic frequency for G6PD 563c.C>T was 0.0285 detected in 6 of 210 X-chromosomes in Southern Pakistan. Frequency for this G6PD allele was 0.0364 in malaria-patients and 0.0200 in healthy individuals. Large studies including females are needed to elucidate the true

  12. Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.

    Science.gov (United States)

    Enwere, Emeka K; Kornaga, Elizabeth N; Dean, Michelle; Koulis, Theodora A; Phan, Tien; Kalantarian, Maria; Köbel, Martin; Ghatage, Prafull; Magliocco, Anthony M; Lees-Miller, Susan P; Doll, Corinne M

    2017-04-01

    Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells. We identified 120 patients with locally advanced cervical cancer treated with radical chemoradiotherapy, and built tissue microarrays from their formalin-fixed, paraffin-embedded pre-treatment biopsies. We used conventional brightfield and fluorescence immunohistochemistry to detect PD-L1, and quantified protein expression using both manual pathologist scoring and automated software analysis. We also evaluated the effect of PD-L1 expression in tumors, along with the presence and density of intra-tumoral CD8 + T cells, on patient survival outcomes. Approximately 96% of the tumor samples expressed PD-L1, as determined using quantitative software analysis. Neither expression of PD-L1 nor density of CD8 + T cells was associated with progression-free or overall survival. However, there was a trend towards worse progression-free survival in patients whose tumors expressed PD-L1 but lacked CD8 + T cells (hazard ratio=0.43 (0.18-1.01), P=0.053). Nevertheless, the high percentage of cervical cancer tumor samples expressing PD-L1 suggests that anti-PD-L1 or anti-PD-1 therapies are potential treatment options for this patient population.

  13. Immuno-Oncology Biomarkers for Gastric and Gastroesophageal Junction Adenocarcinoma: Why PD-L1 Testing May Not Be Enough.

    Science.gov (United States)

    Weinberg, Benjamin A; Xiu, Joanne; Hwang, Jimmy J; Shields, Anthony F; Salem, Mohamed E; Marshall, John L

    2018-04-27

    The treatment of patients with advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinomas has been transformed by the U.S. Food and Drug Administration approval of pembrolizumab. Tumor and adjacent tissue must stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. However, some patients with PD-L1-negative tumors also benefit from pembrolizumab. High microsatellite instability (MSI) and tumor mutational load (TML) are positive predictive biomarkers for immune checkpoint inhibition (ICI) in other tumors. We sought to identify more patients who could benefit from ICI using alternative PD-L1 thresholds, MSI, and TML. Tumor specimens underwent next-generation sequencing (NGS) and PD-L1 testing using immunohistochemistry. NGS was used to determine TML and MSI. We profiled 581 G/GEJ adenocarcinoma specimens. PD-L1 staining was scored for intensity (0, none; 1+, weak; 2+, moderate; 3+, strong). Using 2+ staining at a 5% threshold, 9.3% of tumors were PD-L1 positive, and using 1+ staining at 1%, 16.2% were PD-L1 positive. 6.9% of tumors had high MSI. High TML (≥17 mutations per megabase) was seen in 6.9%, and medium TML (≥7) was seen in 56.5% of tumors. Thirty (5.2%) PD-L1-negative tumors at the 1+, 1% threshold had high TML or high MSI. Primary tumors had higher rates of high TML (8.8% vs. 3.9%; p  = .0377) and high MSI (8.5% vs. 3.9%; p  = .0471) than metastases. PD-L1 testing alone fails to detect patients who may benefit from ICI. Lower PD-L1 thresholds and TML testing should be considered in future clinical trials. Pembrolizumab is approved by the U.S. Food and Drug Administration for patients with refractory gastric and gastroesophageal cancers if the tumor and adjacent tissue stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. Tumor mutational load, microsatellite instability (MSI), and alternative PD-L1 testing thresholds may serve as

  14. One-pot synthesis of Pd-Pt@Pd core-shell nanocrystals with enhanced electrocatalytic activity for formic acid oxidation

    KAUST Repository

    Yuan, Qiang; Huang, Dabing; Wang, Honghui; Zhou, Zhiyou; Wang, Qingxiao

    2014-01-01

    Well-defined Pd-Pt@Pd core-shell nanocrystals with a Pd-Pt alloy core and a conformal Pd shell of ~2-3 nm were directly synthesized through a one-pot, aqueous solution approach without any preformed Pd or Pt seeds. These Pd-Pt@Pd core

  15. Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng-Fei Wang

    2017-10-01

    Full Text Available Background: Treatment of cancers with programmed cell death protein 1 (PD-1 pathway inhibitors can lead to immune-related adverse events (irAEs, which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs.Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence.Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC, colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis, endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency, digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin, respiratory system (pneumonitis, lung infiltration, and interstitial lung disease, and urinary system (increased creatinine, nephritis, and renal failure. In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73–32.61; I2, 92.80 in any grade and 6.10% (95% CI, 4.85–7.64; I2, 52.00 in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%.Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types.

  16. RAC1 P29S regulates PD-L1 expression in melanoma

    Science.gov (United States)

    Vu, Ha Linh; Rosenbaum, Sheera; Purwin, Timothy J.; Davies, Michael A.; Aplin, Andrew E.

    2015-01-01

    Summary Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5–9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD-L1 is a candidate biomarker for increased benefit from treatment with anti-PD1 or anti-PD-L1 antibodies. PMID:26176707

  17. (G6PD) in stored blood

    African Journals Online (AJOL)

    Red blood cell viability in stored blood determines successful transfusion. Glucose-6-phosphate dehydrogenase (G6PD) activity has been shown to maintain red blood cell membrane integrity. This study was, therefore, aimed at estimating the G6PD activity in stored blood bags at the blood bank of the University of Nigeria ...

  18. H-H interactions in Pd

    DEFF Research Database (Denmark)

    Christensen, O. B.; Ditlevsen, Peter; Jacobsen, Karsten Wedel

    1989-01-01

    -medium theory to calculate total energies we show the same tendency for the short-range part of the H-H interaction when two H atoms are squeezed into a single site in Pd or PdH. At longer range (of the order a lattice constant) there is an attractive, lattice-mediated H-H interaction. On the basis...

  19. Serum Bicarbonate And Survival In Peritoneal Dialysis (Pd: Comparison With Hemodialysis (Hd

    Directory of Open Access Journals (Sweden)

    Tania Sharma

    2012-06-01

    Full Text Available Correction of metabolic acidosis is one of the goals of effective dialysis. The KDOQI guidelines recommend serum bicarbonate >22 meq/L irrespective of dialysis modality. Since the measured bicarbonate reflects the steady state in PD patients and the lowest inter-dialytic value in HD patients, we compared the survival predictability of serum bicarbonate 10,400 PD and 110,951 HD patients treated in DaVita facilities from 7/2001-6/2006 with follow-up through 6/2007. PD patients were substantially less likely to have lower serum bicarbonate (adjusted odds, 22 meq/L for all end-stage renal disease irrespective of dialysis modality.fx1

  20. Multiplexed Immunofluorescence Reveals Potential PD-1/PD-L1 Pathway Vulnerabilities in Craniopharyngioma.

    Science.gov (United States)

    Coy, Shannon; Rashid, Rumana; Lin, Jia-Ren; Du, Ziming; Donson, Andrew M; Hankinson, Todd C; Foreman, Nicholas K; Manley, Peter E; Kieran, Mark W; Reardon, David A; Sorger, Peter K; Santagata, Sandro

    2018-03-02

    Craniopharyngiomas are neoplasms of the sellar/parasellar region that are classified into adamantinomatous (ACP) and papillary (PCP) subtypes. Surgical resection of craniopharyngiomas is challenging, and recurrence is common, frequently leading to profound morbidity. BRAF V600E mutations render PCP susceptible to BRAF/MEK inhibitors, but effective targeted therapies are needed for ACP. We explored the feasibility of targeting the PD-1/PD-L1 immune checkpoint pathway in ACP and PCP. We mapped and quantified PD-L1 and PD-1 expression in ACP and PCP resections using immunohistochemistry, immunofluorescence, and RNA in situ hybridization. We used tissue-based cyclic immunofluorescence (t-CyCIF) to map the spatial distribution of immune cells and characterize cell cycle and signaling pathways in ACP tumor cells which intrinsically express PD-1. All ACP (15±14% of cells, n=23, average±S.D.) and PCP (35±22% of cells, n=18) resections expressed PD-L1. In ACP, PD-L1 was predominantly expressed by tumor cells comprising the cyst-lining. In PCP, PD-L1 was highly-expressed by tumor cells surrounding the stromal fibrovascular cores. ACP also exhibited tumor cell-intrinsic PD-1 expression in whorled epithelial cells with nuclear-localized beta-catenin. These cells exhibited evidence of elevated mTOR and MAPK signaling. Profiling of immune populations in ACP and PCP showed a modest density of CD8+ T-cells. ACP exhibit PD-L1 expression in the tumor cyst-lining and intrinsic PD-1 expression in cells proposed to comprise an oncogenic stem-like population. In PCP, proliferative tumor cells express PD-L1 in a continuous band at the stromal-epithelial interface. Targeting PD-L1 and/or PD-1 in both subtypes of craniopharyngioma might therefore be an effective therapeutic strategy.

  1. Translation and discriminative validation of the STarT Back Screening Tool into Danish

    DEFF Research Database (Denmark)

    Morsø, Lars; Albert, Hanne; Kent, Peter

    2011-01-01

    OBJECTIVE: The STarT Back Screening Tool (STarT) is a nine-item patient self-report questionnaire that classifies low back pain patients into low, medium or high risk of poor prognosis. When assessed by GPs, these subgroups can be used to triage patients into different evidence-based treatment pa...

  2. PD-1 signaling and inhibition in AML and MDS.

    Science.gov (United States)

    Haroun, Faysal; Solola, Sade A; Nassereddine, Samah; Tabbara, Imad

    2017-09-01

    Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.

  3. Anti-tumor immunotherapy by blockade of the PD-1/PD-L1 pathway with recombinant human PD-1-IgV.

    Science.gov (United States)

    Zhang, C; Wu, S; Xue, X; Li, M; Qin, X; Li, W; Han, W; Zhang, Y

    2008-01-01

    Blockade of the programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway can delay tumor growth and prolong the survival of tumor-bearing mice. The extracellular immunoglobulin (Ig) V domain of PD-1 is important for the interaction between PD-1 and PD-L1, suggesting that PD-1-IgV may be a potential target for anti-tumor immunotherapy. The extracellular sequence of human PD-1-IgV (hPD-1-IgV) was expressed in Escherichia coli and purified. The anti-tumor effect of hPD-1-IgV on tumor-bearing mice was tested. hPD-1-IgV recombinant protein could bind PD-L1 at molecular and cellular levels and enhance Cytotoxic T Lymphocyte (CTL) activity and anti-tumor effect on tumor-bearing mice in vivo. The percentage of CD4(+)CD25(+) T cells in tumor-bearing mice was decreased compared with control mice after administration of the recombinant protein. Our results suggest that inhibition of the interaction between PD-1 and PD-L1 by hPD-1-IgV may be a promising strategy for specific tumor immunotherapy.

  4. Severe acute haemolytic anaemia associated with severe methaemoglobinaemia in a G6PD-deficient man.

    Science.gov (United States)

    Rehman, Abdul; Shehadeh, Mohanad; Khirfan, Diala; Jones, Akhnuwhkh

    2018-03-28

    Methaemoglobin is a form of haemoglobin in which the ferrous (Fe 2+ ) ion contained in the iron-porphyrin complex of haem is oxidised to its ferric (Fe 3+ ) state. Methaemoglobinaemia, the presence of methaemoglobin in the blood, is most commonly treated with methylene blue. However, methylene blue cannot be used in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency as it is ineffective in such patients and it can worsen G6PD deficiency haemolysis. We report the case of a 30-year-old man who presented with clinical features of G6PD deficiency-associated haemolysis and was found to have severe methaemoglobinaemia (35%). He was administered blood transfusions and intravenous ascorbic acid. His methaemoglobinaemia resolved within 24 hours. This case demonstrates the successful management of a patient with severe methaemoglobinaemia in the setting of G6PD deficiency haemolysis. Emergency physicians should be aware of the possible co-occurrence of severe methaemoglobinaemia in a patient with G6PD deficiency haemolysis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Start II, red ink, and Boris Yeltsin

    International Nuclear Information System (INIS)

    Arbatov, A.

    1993-01-01

    Apart from the vulnerability implied by the START II treaty, it will bear the burden of the general political opposition to the Yeltsin administration. START II will be seen as part of an overall Yeltsin-Andrei Kozyrev foreign policy that is under fire for selling out Russian national interests in Yugoslavia, the Persian Gulf, and elsewhere. This article discusses public opinion concerning START II, the cost of its implementation, and the general purpose of the treaty

  6. Starting a business through a franchise

    OpenAIRE

    Dubravka Mahaček; Maja Martinko Lihtar

    2013-01-01

    A business can be launched by establishing a new entity, purchasing an existing entity or through a franc - hise. There are certain prerequisites for starting a business, the most important ones being a quality idea and start-up capital. Potential start-up difficulties are inadequate financing, existing competition as well as the process of building your own market position. By purchasing an existing business some risks may be avoided and the opportunity for gaining profit may ...

  7. From START to NEW START. The dilemma and future of nuclear disarmament; Von START zu NEW START. Das Dilemma und die Zukunft der Nuklearen Abruestung

    Energy Technology Data Exchange (ETDEWEB)

    Plettenberg, Lars

    2012-07-01

    The report describes the existing four agreements on nuclear disarmament: START I (1991). START II (1993), SORT (2002) and NEW START (2010). The chapter on the dependence between nuclear disarmament and strategic stability covers the issues mutual assured destruction (MAD), credibility, overkill capacity; the role of nuclear weapons in the national strategies of the USA and NATO, Russia, Great Britain, France, China and the other nuclear states. Ways out of MAD include disarmament, de-alerting and mutual assured protection (MAP).

  8. Changes in geriatric nutritional risk index and risk of major adverse cardiac and cerebrovascular events in incident peritoneal dialysis patients

    Directory of Open Access Journals (Sweden)

    Mi Jung Lee

    2017-12-01

    Full Text Available Background: Geriatric nutritional risk index (GNRI is a validated nutritional assessment method, and lower GNRI values are closely associated with adverse clinical outcomes in dialysis patients. This study investigated the impact of changes in GNRI during the first year of dialysis on cardiovascular outcomes in incident peritoneal dialysis (PD patients. Methods: We reviewed medical records in 133 incident PD patients to determine GNRI at the start of PD and after 12 months. Patients were categorized into improved (delta GNRI > 0 and worsening/stationary (delta GNRI ≤ 0 groups. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs. Results: During a mean follow-up of 51.1 months, the primary outcome was observed in 42 patients (31.6%. The baseline GNRI at PD initiation was not significantly associated with MACCEs (log-rank test, P = 0.40. However, the cumulative event-free rate was significantly lower in the worsening or stationary GNRI group than in the improved group (log-rank test, P = 0.004. Multivariate Cox analysis revealed that a worsening or stationary GNRI was independently associated with higher risk for MACCEs (hazard ratio, 2.47; 95% confidence interval, 1.15–5.29; P = 0.02. In subgroup analysis, patients with worsening or stationary GNRI were at significantly greater risk for MACCEs in both the lower (P = 0.04 and higher (P = 0.01 baseline GNRI groups. Conclusion: Baseline GNRI was not associated with MACCEs, but patients with deteriorating or stationary nutritional status were at significantly greater risk for MACCEs, suggesting that serial monitoring of nutritional status is important to stratify cardiovascular risk in incident PD patients.

  9. Investigating unexpected magnetism of mesoporous silica-supported Pd and PdO nanoparticles

    KAUST Repository

    Song, Hyon Min

    2015-01-13

    The synthesis and magnetic behavior of matrix-supported Pd and PdO nanoparticles (NPs) are described. Mesoporous silica with hexagonal columnal packing is selected as a template, and the impregnation method with thermal annealing is used to obtain supported Pd and PdO NPs. The heating rate and the annealing conditions determine the particle size and the phase of the NPs, with a fast heating rate of 30 °C/min producing the largest supported Pd NPs. Unusual magnetic behaviors are observed. (1) Contrary to the general belief that smaller Pd NPs or cluster size particles have higher magnetization, matrix-supported Pd NPs in this study maintain the highest magnetization with room temperature ferromagnetism when the size is the largest. (2) Twin boundaries along with stacking faults are more pronounced in these large Pd NPs and are believed to be the reason for this high magnetization. Similarly, supported PdO NPs were prepared under air conditions with different heating rates. Their phase is tetragonal (P42/mmc) with cell parameters of a = 3.050 Å and c = 5.344 Å, which are slightly larger than in the bulk phase (a = 3.03 Å, c = 5.33 Å). Faster heating rate of 30 °C/min also produces larger particles and larger magnetic hysteresis loop, although magnetization is smaller and few twin boundaries are observed compared to the supported metallic Pd NPs.

  10. Dual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells.

    Science.gov (United States)

    Sasidharan Nair, Varun; Toor, Salman M; Ali, Bassam R; Elkord, Eyad

    2018-05-02

    Breast cancer is the most commonly diagnosed cancer, and it is a leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) constitutes 15% of breast cancer and shows distinct metastasis profiles with poor prognosis. Strong PD-L1 expression has been observed in some tumors, supporting their escape from immune surveillance. Targeting PD-L1 could be a promising therapeutic approach in breast cancer patients. We investigated potential molecular mechanisms for constitutive expression of PD-L1 by inhibiting upstream STAT1 and STAT3 signals. PD-L1 expression in three breast cancer cell lines was measured using quantitative PCR and western blotting. Activation of STAT1 and STAT3 was blocked using pharmacological inhibitors and siRNA. The mechanism underlying the constitutive expression of PD-L1 was investigated using ChIP and co-immunoprecipitation assays. We found that individual inhibition of STAT1 and STAT3 activation partially downregulated PD-L1, while combined inhibition completely downregulated PD-L1 expression. Moreover, our results suggest that pSTAT1-pSTAT3 dimerize in cytosol and translocate to the nucleus, where they bind to PD-L1 promoter and induce PD-L1 expression. These findings provide a rationale for combined targeting of STAT1 and STAT3 for the development of immune-based cancer therapies for down regulation of PD-L1 expression.

  11. Characterization of G6PD genotypes and phenotypes on the northwestern Thailand-Myanmar border.

    Directory of Open Access Journals (Sweden)

    Germana Bancone

    Full Text Available Mutations in the glucose-6-phosphate dehydrogenase (G6PD gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST, G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A genotype. The remaining subjects had Chinese-4 (392G>T, Viangchan (871G>A, Açores (595A>G, Seattle (844G>C and Mediterranean (563C>T variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes.

  12. Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer

    DEFF Research Database (Denmark)

    Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick

    2014-01-01

    change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse......OBJECTIVE: To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics....... PATIENTS AND METHODS: The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3...

  13. Suicidal behavior among Turkish patients with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Ozdilek B

    2014-03-01

    Full Text Available Betul Ozdilek,1 Bulent Kadri Gultekin21Department of Neurology, 2Department of Psychiatry, Erenkoy Mental Health and Neurology Training and Research Hospital, Istanbul, TurkeyObjective: To investigate the predictors of suicidal ideation and attempts among Turkish Parkinson’s disease (PD patients.Materials and methods: The study comprised 120 patients with PD. Clinical findings were obtained by using the Unified Parkinson’s Disease Rating Scale. Disease severity was measured by the Hoehn and Yahr staging scale, and the Schwab and England Activities of Daily Living scale was used for patient disability. Psychiatric evaluation was performed by the same psychiatrist using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV Axis I Disorders. Severity of depression was measured with the Hamilton Depression Rating Scale. Suicidal ideation and attempts were considered positive if experienced during the patient’s lifetime. The Suicide Probability Scale was used to assess the risk of suicide. Data were analyzed by logistic regression models to identify variables associated with suicidal ideation and attempts.Results: Based on logistic regression analysis, education level, age of disease onset, disease duration, depression, and history of impulse-control disorder (ICD behaviors were significant predictors of suicidal ideation. The risk rate in the presence of depression and history of ICD behaviors was increased by 5.92 and 4.97, respectively. Additionally, lifetime prevalence of suicidal ideation was found in 11.6% (14 of 120 of PD patients, although no patient had ever attempted suicide.Conclusion: Turkish patients with PD who exhibit a high risk for suicidal ideation also experience disease starting at an earlier age, longer disease duration, presence of depression, and ICD behaviors, and should be monitored carefully.Keywords: Parkinson’s disease, suicidal behavior, risk factors

  14. PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer.

    Science.gov (United States)

    Tsao, M-S; Le Teuff, G; Shepherd, F A; Landais, C; Hainaut, P; Filipits, M; Pirker, R; Le Chevalier, T; Graziano, S; Kratze, R; Soria, J-C; Pignon, J-P; Seymour, L; Brambilla, E

    2017-04-01

    The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC. Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy. Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy. PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients. © The Author 2017. Published by

  15. Production of verbs related to body movement in amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD).

    Science.gov (United States)

    Cousins, Katheryn A Q; Ash, Sharon; Grossman, Murray

    2018-03-01

    Theories of grounded cognition propose that action verb knowledge relies in part on motor processing regions, including premotor cortex. Accordingly, impaired action verb knowledge in patients with amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD) is thought to be due to motor system degeneration. Upper motor neuron disease in ALS degrades the motor cortex and related pyramidal motor system, while disease in PD is centered in the basal ganglia and can spread to frontostriatal areas that are important to language functioning. These anatomical distinctions in disease may yield subtle differences in the action verb impairment between patient groups. Here we compare verbs where the body is the agent of the action to verbs where the body is the theme. To examine the role of motor functioning in body verb production, we split patient groups into patients with high motor impairment (HMI) and those with low motor impairment (LMI), using disease-specific measures of motor impairment. Regression analyses assessed how verb production in ALS and PD was related to motor system atrophy. We find a dissociation between agent- and theme-body verbs in ALS: ALS HMI were impaired for agent body verbs but not theme verbs, compared to ALS LMI. This dissociation was not present in PD patients, who instead show depressed production for all body verbs. Although patients with cognitive impairment were excluded from this study, cognitive performance significantly correlated with the production of theme verbs in ALS and cognitive/stative verbs in PD. Finally, regression analyses related the agent-theme dissociation in ALS to grey matter atrophy of premotor cortex. These findings support the view that motor dysfunction and disease in premotor cortex contributes to the agent body verb deficit in ALS, and begin to identify some distinct characteristics of impairment for verbs in ALS and PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Getting started with SBT for Scala

    CERN Document Server

    Saxena, Shiti

    2013-01-01

    A practical and fast-paced guide, Getting Started with SBT for Scala walks you through the setup of Scala projects in SBT with sample code for common as well as critical scenarios.Getting Started with SBT for Scala is for developers working on Scala projects who are interested in learning and utilizing Simple Build Tool to manage the build process.

  17. Families & the North Carolina Smart Start Initiative.

    Science.gov (United States)

    Lowman, Betsy; Bryant, Donna; Zolotor, Adam

    Smart Start is North Carolina's partnership between state government and local leaders, service providers, and families to better serve children under 6 years and their families. This study examined characteristics of families participating in Smart Start, their child care arrangements and family activities, and their need for and use of community…

  18. Start-up analysis for marketing strategy.

    Science.gov (United States)

    Griffith, M J; Baloff, N

    1984-01-01

    The complex start-up effect on utilization of health care services is too often overlooked or underestimated by marketing planners, leading to a range of negative consequences for both the users of services and the provider organization. Start-up analysis allows accurate estimation of these utilization effects for coordinated strategic planning among marketing finance, and operations.

  19. Head Start Impact Study. Technical Report

    Science.gov (United States)

    Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Shapiro, Gary; Broene, Pam; Jenkins, Frank; Fletcher, Philip; Quinn, Liz; Friedman, Janet; Ciarico, Janet; Rohacek, Monica; Adams, Gina; Spier, Elizabeth

    2010-01-01

    This Technical Report is designed to provide technical detail to support the analysis and findings presented in the "Head Start Impact Study Final Report" (U.S. Department of Health and Human Services, January 2010). Chapter 1 provides an overview of the Head Start Impact Study and its findings. Chapter 2 provides technical information on the…

  20. PD-1/PD-L signaling pathway in chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    TAO Lilin

    2016-12-01

    Full Text Available Hepatitis B is one of the major diseases that affect the health of Chinese people, and chronic hepatitis B virus (HBV infection can lead to disease progression. Programmed death-1 (PD-1 discovered in recent years is an important coordinated stimulus molecule which belongs to the B7/CD28 family. After its binding with programmed death ligand (PD-L, it can regulate the activation, differentiation, and proliferation of T lymphocytes. PD-1 and its ligand are differently expressed in different stages of chronic HBV infection. The interaction between PD-1 and its ligand in different immune cells induces immune tolerance in human body and finally leads to the chronicity of HBV infection. Blocking the PD-1/PD-L signaling pathway through different ways can improve T cell exhaustion, suggesting that this might be one of the directions of antiviral therapy in future.

  1. Effect of PD-WEBB training on balance impairment and falls in people with Parkinson’s disease%PD-WEBB训练对帕金森病平衡障碍和跌倒的影响

    Institute of Scientific and Technical Information of China (English)

    谷绍娟; 宋治; 范学军; 陈茹; 郑文; 严文广

    2013-01-01

    Objective:To determine the effect of Parkinson’s disease-weight bearing exercise for better balance (PD-WEBB) exercise on balance impairment and falls in people with Parkinson's disease (PD).Methods:A single-blind, randomized controlled clinical trial was conducted. The falls efficacy scale score, unified Parkinson disease rating scale (UPDRS) score and Mini-BESTest score were measured and compared between a PD-WEBB group and a control group. Results:hTe falls effcacy scale score, UPDRS-2 score, UPDRS-3 score and Mini-BESTest score were improved in the PD-WEBB group compared with the control group (P Conclusion:PD-WEBB training can significantly improve the balance impairment and quality of life to prevent falls. PD-WEBB training is suitable for PD patients in China, and is a reasonable, effective and sustainable training of family and community assessment model.%目的:评价PD-WEBB训练对帕金森病(Parkinson’s disease,PD)患者平衡障碍和跌倒的影响。方法:采用随机、单盲、对照设计分析PD-WEBB训练8周前后PD-WEBB组与对照组PD患者跌倒功效量表(falls effcacy scale,FES)评分、帕金森病综合评分量表(UPDRS)评分和Mini-Balance Evaluation Systems Test (Mini-BESTest)评分的变化。结果:8周后PD-WEBB组FES评分、UPDRS-2评分、UPDRS-3评分和Mini-BESTest评分较对照组有明显变化(P<0.05),而两组间UPDRS-1评分变化不明显。结论:PD-WEBB训练可以明显改善PD患者的平衡障碍,提高患者日常生活质量,预防跌倒。PD-WEBB训练适合中国PD患者,是一种合理有效的可持续的家庭训练模式。

  2. Unipolar depression suddenly switches to hypomania in a patient who has just started taking venlafaxine. A case study [Acute stemmingsomslag naar hypomanie bij een pati�nte met een unipolaire depressie direct na starten van venlafaxine

    NARCIS (Netherlands)

    Krol, D.G.H.; Nolen, W.A.

    2006-01-01

    A woman with a recurrent episode of a depression that hitherto had been unipolar developed a hypomania the day after her treatment with paroxetine 20 mg/day was switched to venlafaxine 75 mg/day. The hypomanic symptoms subsided gradually as the dosage was reduced and the patient thereafter remained

  3. Healthcare Data Analytics for Parkinson's Disease Patients: A Study of Hospital Cost and Utilization in the United States.

    Science.gov (United States)

    Mukherjee, Sunanda; Wu, Huanmei; Jones, Josette

    2016-01-01

    Parkinson's Disease (PD), a prevalent problem, especially for the aged populations, is a progressive but non-fatal nervous system disorder. PD patients have special motor as well as non-motor symptoms over time. There are several limitations in the study of PD such as unavailability of data, proper diagnosis and treatment methods. These limitations significantly reduce the quality of PD patient life quality, either directly or indirectly. PD also imposes great financial burdens to PD patients and their family. This project aims to analyze the most common reasons for PD patient hospitalization, review complications that occur during inpatient stays, and measure the costs associated with PD patient characteristics. Using the HCUP NIS data, comprehensive data analysis has been performed. The results are customized visualized using Tableau and other software systems. The preliminary findings sheds light into how to improve the life quality of PD patients.

  4. Theoretical analysis of hydrogen chemisorption on Pd(111), Re(0001) and PdML/Re(0001), ReML/Pd(111) pseudomorphic overlayers

    DEFF Research Database (Denmark)

    Pallassana, Venkataraman; Neurock, Matthew; Hansen, Lars Bruno

    1999-01-01

    not appear to provide an independent parameter for assessing surface reactivity. The weak chemisorption of hydrogen on the Pd-ML/Re(0001) surface relates to substantial lowering of the d-band center of Pd, when it is pseudomorphically deposited as a monolayer on a Re substrate. [S0163-1829(99)00331-2].......Gradient-corrected density-functional theory (DFT-GGA) periodic slab calculations have been used to analyze the binding of atomic hydrogen on monometallic Pd(111), Re(0001), and bimetallic Pd-mL/Re(0001) [pseudomorphic monolayer of Pd(111) on Re(0001)] and Re-ML/Pd(111) surfaces. The computed...

  5. Nanostructure analysis of friction welded Pd-Ni-P/Pd-Cu-Ni-P metallic glass interface

    International Nuclear Information System (INIS)

    Ohkubo, T.; Shoji, S.; Kawamura, Y.; Hono, K.

    2005-01-01

    Friction welded Pd 40 Ni 40 P 20 /Pd 40 Cu 30 Ni 10 P 20 metallic glass interface has been characterized by energy filtering transmission electron microscopy. The interface is fully amorphous with a gradual compositional change of Cu and Ni in the range of 30 nm. By annealing above T g , the interdiffusion of Cu and Ni progressed in the supercooled liquid region, and the crystallization occurred from the Pd 40 Ni 40 P 20 glass

  6. Cytotoxicity of Pd nanostructures supported on PEN: Influence of sterilization on Pd/PEN interface

    Energy Technology Data Exchange (ETDEWEB)

    Polívková, M., E-mail: polivkoa@vscht.cz [Department of Solid State Engineering, University of Chemistry and Technology Prague, 166 28 Prague (Czech Republic); Siegel, J. [Department of Solid State Engineering, University of Chemistry and Technology Prague, 166 28 Prague (Czech Republic); Rimpelová, S. [Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, 166 28 Prague (Czech Republic); Hubáček, T. [Institute of Hydrobiology, Biology Centre of the AS CR, 370 05 Ceske Budejovice (Czech Republic); Kolská, Z. [Materials Centre of Usti n. L., J.E. Purkyne University, 400 96 Usti nad Labem (Czech Republic); Švorčík, V. [Department of Solid State Engineering, University of Chemistry and Technology Prague, 166 28 Prague (Czech Republic)

    2017-01-01

    Non-conventional antimicrobial agents, such as palladium nanostructures, have been increasingly used in the medicinal technology. However, experiences uncovering their harmful and damaging effects to human health have begun to appear. In this study, we have focused on in vitro cytotoxicity assessment of Pd nanostructures supported on a biocompatible polymer. Pd nanolayers of variable thicknesses (ranging from 1.1 to 22.4 nm) were sputtered on polyethylene naphthalate (PEN). These nanolayers were transformed by low-temperature post-deposition annealing into discrete nanoislands. Samples were characterized by AFM, XPS, ICP-MS and electrokinetic analysis before and after annealing. Sterilization of samples prior to cytotoxicity testing was done by UV irradiation, autoclave and/or ethanol. Among the listed sterilization techniques, we have chosen the gentlest one which had minimal impact on sample morphology, Pd dissolution and overall Pd/PEN interface quality. Cytotoxic response of Pd nanostructures was determined by WST-1 cell viability assay in vitro using three model cell lines: mouse macrophages (RAW 264.7) and two types of mouse embryonic fibroblasts (L929 and NIH 3T3). Finally, cell morphology in response to Pd/PEN was evaluated by means of fluorescence microscopy. - Highlights: • Annealing of Pd nanolayers on PEN resulted to Pd aggregation and formation of discrete nanoislands. • UV treatment was found as the gentlest sterilization method in term of physicochemical properties of Pd/PEN interface. • Autoclaving and chemical sterilization by ethanol resulted into remarkable changes of Pd/PEN interface. • Cytotoxicity of Pd samples was insignificant. • Pd nanostructures are potentially applicable as health-unobjectionable antibacterial coatings of medical devices.

  7. Preparation of 103Pd seed-molecular plating of 103Pd onto silver rod

    International Nuclear Information System (INIS)

    Zhang Chunfu; Wang Yongxian; Tian Haibin; Yin Duanzhi

    2002-01-01

    A method for 103 Pd 'molecular plating' onto the surface of a silver rod is reported. The optimal composition of the plating bath is as follows: palladium chloride 0.1 mol/l, formaldehyde 2 mol/l, nitric acid 1 mol/l, and formic acid 0.4 mol/l. The 103 Pd molecular plating procedure will last 25 min at 30 deg. C. This article provides a valuable experience for the preparation of 103 Pd brachytherapy seed

  8. Preparation of 103Pd seeds. Part 2. 'Molecular Plating' of 103Pd onto copper rod

    International Nuclear Information System (INIS)

    Chunfu Zhang; Yongxian Wang; Haibin Tian; Duanzhi Yin

    2002-01-01

    A method for 103 Pd 'molecular plating' onto the surface of the copper rod is reported. The optimal composition of the plating bath was: palladium chloride 2 g/l, ammonium hydroxide (28%) 150 ml/l, sodium hypophosphite 12 g/l, and ammonium chloride 37 g/l. The whole procedure of 103 Pd 'molecular plating' will last 50 minutes at 40 deg C. Valuable experience for the preparation of 103 Pd seeds is provided. (author)

  9. Cerebral oxygen metabolism in patients with early Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Cumming, Paul; Østergaard, Karen

    2012-01-01

    ) and cerebral blood flow (CBF) PET scans from PD patients and healthy controls. MATERIALS AND METHODS: Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO(2) and CBF. Between-group differences were evaluated for absolute data and intensity...... in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD....

  10. PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Thompson, Elizabeth D; Taube, Janis M; Asch-Kendrick, Rebecca J; Ogurtsova, Aleksandra; Xu, Haiying; Sharma, Rajni; Meeker, Alan; Argani, Pedram; Emens, Leisha A; Cimino-Mathews, Ashley

    2017-11-01

    Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (50%). The average immune cell subtype per high-power field was quantitatively scored. The percentage PD-L1 labeling on tumor-infiltrating lymphocytes was scored as none, focal (lobular carcinomas contained PD-L1 + tumor-infiltrating lymphocytes with the majority showing 1+ immune infiltrates with focal-moderate PD-L1 labeling. PD-L1 was expressed by tumor cells in 17% of lobular carcinomas. In contrast to ductal carcinomas, there was no correlation between the immune infiltrate density, the PD-L1 expression by lobular carcinoma cells, tumor grade, or the expression of estrogen receptor or human epidermal growth factor receptor-2. However, both the tumor-infiltrating lymphocyte density and the average CD8 + T-cell counts correlated with immune cell PD-L1 status (P=0.004 and 0.03, respectively). Similar to breast ductal carcinomas, PD-L1 + lobular breast carcinomas had higher numbers of PD-L1 + tumor-infiltrating lymphocytes (63%) than PD-L1 - lobular carcinomas (23%; P=0.04). These data show that a subset of primary breast lobular carcinomas both express PD-L1 on tumor cells and contain PD-L1 + tumor-infiltrating lymphocytes, suggesting the possibility of both constitutive and adaptive PD-L1 expression. Together, these results support immunotherapy as a potential treatment for a subset of patients with primary invasive lobular breast carcinomas.

  11. Pd-nanoparticles cause increased toxicity to kiwifruit pollen compared to soluble Pd(II)

    International Nuclear Information System (INIS)

    Speranza, Anna; Leopold, Kerstin; Maier, Marina; Taddei, Anna Rita; Scoccianti, Valeria

    2010-01-01

    In the present study, endpoints including in vitro pollen performance (i.e., germination and tube growth) and lethality were used as assessments of nanotoxicity. Pollen was treated with 5-10 nm-sized Pd particles, similar to those released into the environment by catalytic car exhaust converters. Results showed Pd-nanoparticles altered kiwifruit pollen morphology and entered the grains more rapidly and to a greater extent than soluble Pd(II). At particulate Pd concentrations well below those of soluble Pd(II), pollen grains experienced rapid losses in endogenous calcium and pollen plasma membrane damage was induced. This resulted in severe inhibition and subsequent cessation of pollen tube emergence and elongation at particulate Pd concentrations as low as 0.4 mg L -1 . Particulate Pd emissions related to automobile traffic have been increasing and are accumulating in the environment. This could seriously jeopardize in vivo pollen function, with impacts at an ecosystem level. - Nanoparticulate Pd - which resembles emissions from automobile catalysts - affects pollen to a higher extent than soluble Pd.

  12. Pd-nanoparticles cause increased toxicity to kiwifruit pollen compared to soluble Pd(II)

    Energy Technology Data Exchange (ETDEWEB)

    Speranza, Anna, E-mail: anna.speranza@unibo.i [Dipartimento di Biologia, Universita di Bologna, via Irnerio 42, 40126 Bologna (Italy); Leopold, Kerstin, E-mail: kerstin.leopold@lrz.tu-muenchen.d [Arbeitsgruppe fuer Analytische Chemie, Technische Universitaet Muenchen, Garching (Germany); Maier, Marina, E-mail: marina.maier@ch.tum.d [Arbeitsgruppe fuer Analytische Chemie, Technische Universitaet Muenchen, Garching (Germany); Taddei, Anna Rita, E-mail: artaddei@unitus.i [CIME, Universita della Tuscia, Viterbo (Italy); Scoccianti, Valeria, E-mail: valeria.scoccianti@uniurb.i [Dipartimento di Scienze dell' Uomo, dell' Ambiente e della Natura, Universita di Urbino ' Carlo Bo' , Urbino (Italy)

    2010-03-15

    In the present study, endpoints including in vitro pollen performance (i.e., germination and tube growth) and lethality were used as assessments of nanotoxicity. Pollen was treated with 5-10 nm-sized Pd particles, similar to those released into the environment by catalytic car exhaust converters. Results showed Pd-nanoparticles altered kiwifruit pollen morphology and entered the grains more rapidly and to a greater extent than soluble Pd(II). At particulate Pd concentrations well below those of soluble Pd(II), pollen grains experienced rapid losses in endogenous calcium and pollen plasma membrane damage was induced. This resulted in severe inhibition and subsequent cessation of pollen tube emergence and elongation at particulate Pd concentrations as low as 0.4 mg L{sup -1}. Particulate Pd emissions related to automobile traffic have been increasing and are accumulating in the environment. This could seriously jeopardize in vivo pollen function, with impacts at an ecosystem level. - Nanoparticulate Pd - which resembles emissions from automobile catalysts - affects pollen to a higher extent than soluble Pd.

  13. Recovery of high-purity metallic Pd from Pd(II)-sorbed biosorbents by incineration.

    Science.gov (United States)

    Won, Sung Wook; Lim, Areum; Yun, Yeoung-Sang

    2013-06-01

    This work reports a direct way to recover metallic palladium with high purity from Pd(II)-sorbed polyethylenimine-modified Corynebacterium glutamicum biosorbent using a combined method of biosorption and incineration. This study is focused on the incineration part which affects the purity of recovered Pd. The incineration temperature and the amount of Pd loaded on the biosorbent were considered as major factors in the incineration process, and their effects were examined. The results showed that both factors significantly affected the enhancement of the recovery efficiency and purity of the recovered Pd. SEM-EDX and XRD analyses were used to confirm that Pd phase existed in the ash. As a result, the recovered Pd was changed from PdO to zero-valent Pd as the incineration temperature was increased from 600 to 900°C. Almost 100% pure metallic Pd was recovered with recovery efficiency above 99.0% under the conditions of 900°C and 136.9 mg/g. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. One-pot synthesis of Pd-Pt@Pd core-shell nanocrystals with enhanced electrocatalytic activity for formic acid oxidation

    KAUST Repository

    Yuan, Qiang

    2014-01-01

    Well-defined Pd-Pt@Pd core-shell nanocrystals with a Pd-Pt alloy core and a conformal Pd shell of ~2-3 nm were directly synthesized through a one-pot, aqueous solution approach without any preformed Pd or Pt seeds. These Pd-Pt@Pd core-shell nanocrystals show an enhanced electrocatalytic activity for formic acid oxidation compared with commercial Pd black. This journal is © 2014 The Royal Society of Chemistry.

  15. Start 2: Thinking one move ahead

    Energy Technology Data Exchange (ETDEWEB)

    Gaines, L.L.

    1991-11-01

    At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush`s historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R&D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.

  16. Start 2: Thinking one move ahead

    Energy Technology Data Exchange (ETDEWEB)

    Gaines, L.L.

    1991-11-01

    At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush's historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.

  17. CO oxidation on PdO surfaces

    DEFF Research Database (Denmark)

    Hirvi, Janne T.; Kinnunen, Toni-Jani J.; Suvanto, Mika

    2010-01-01

    Density functional calculations were performed in order to investigate CO oxidation on two of the most stable bulk PdO surfaces. The most stable PdO(100) surface, with oxygen excess, is inert against CO adsorption, whereas strong adsorption on the stoichiometric PdO(101) surface leads to favorable...... oxidation via the Langmuir–Hinshelwood mechanism. The reaction with a surface oxygen atom has an activation energy of 0.66 eV, which is comparable to the lowest activation energies observed on metallic surfaces. However, the reaction rate may be limited by the coverage of molecular oxygen. Actually...... adsorption, following the Eley–Rideal mechanism and taking advantage of the reaction tunnel provided by the adjacent palladium atom, has an activation energy of only 0.24 eV. The reaction mechanism and activation energy for the palladium activated CO oxidation on the most stable PdO(100)–O surface...

  18. Frequency and Predictors for Late Start of Antiretroviral Therapy in Primary Care Clinics, Kampala, Uganda

    NARCIS (Netherlands)

    Sendagire, Ibrahim; Cobelens, Frank; Kambugu, Andrew; Konde-Lule, Joseph; Schim van der Loeff, Maarten

    2012-01-01

    Background: Access to antiretroviral treatment (ART) has improved greatly in many parts of the world, including Uganda, yet, many patients delay to start ART even when registered within the HIV services. We assessed, in a routine ambulatory care setting, what proportion of patients start ART late

  19. Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Wyss, Natascha; Zwahlen, Marcel; Bohlius, Julia

    2016-01-01

    BACKGROUND:  Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European...

  20. Gut microbiota in patients with Parkinson's disease in southern China.

    Science.gov (United States)

    Lin, Aiqun; Zheng, Wenxia; He, Yan; Tang, Wenli; Wei, Xiaobo; He, Rongni; Huang, Wei; Su, Yuying; Huang, Yaowei; Zhou, Hongwei; Xie, Huifang

    2018-05-16

    Accumulating evidence has revealed alterations in the communication between the gut and brain in patients with Parkinson's disease (PD), and previous studies have confirmed that alterations in the gut microbiome play an important role in the pathogenesis of numerous diseases, including PD. The aim of this study was to determine whether the faecal microbiome of PD patients in southern China differs from that of control subjects and whether the gut microbiome composition alters among different PD motor phenotypes. We compared the gut microbiota composition of 75 patients with PD and 45 age-matched controls using 16S rRNA next-generation-sequencing. We observed significant increases in the abundance of four bacterial families and significant decreases in the abundance of seventeen bacterial families in patients with PD compared to those of the controls. In particular, the abundance of Lachnospiraceae was reduced by 42.9% in patients with PD, whereas Bifidobacteriaceae was enriched in patients with PD. We did not identify a significant difference in the overall microbial composition among different PD motor phenotypes, but we identified the association between specific taxas and different PD motor phenotypes. PD is accompanied by alterations in the abundance of specific gut microbes. The abundance of certain gut microbes was altered depending on clinical motor phenotypes. Based on our findings, the gut microbiome may be a potential PD biomarker. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. PD-L1 blockade with avelumab: A new paradigm for treating Merkel cell carcinoma.

    Science.gov (United States)

    Barkdull, Savannah; Brownell, Isaac

    2017-12-02

    Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. Until recently, no durable treatment options were available for patients with advanced disease. As an immunogenic cancer, MCC was hypothesized to be a candidate for PD-L1/PD-1 targeted therapy. On March 23, 2017 the US Food and Drug Administration granted accelerated approval for avelumab, an anti-PD-L1 monoclonal antibody, for the treatment of metastatic MCC on the basis of the JAVELIN Merkel 200 trial. Here we examine the results and implications of this pivotal study, published in Lancet Oncology by Kaufman et al., as well as current developments in the use of immune-checkpoint therapies for treating patients with MCC.

  2. On nuclear DD synthesis at the initial stage of nanosecond vacuum discharge with deuterium-loaded Pd anode

    Science.gov (United States)

    Kurilenkov, Yu K.; Gus'kov, S. Yu; Karpukhin, V. T.; Oginov, A. V.; Samoylov, I. S.

    2018-01-01

    Earlier, there was demonstrated generation of DD neutrons in an interelectrode medium of a low-energy (˜ 1 J) nanosecond vacuum discharge with a hollow cathode and a deuterium-loaded Pd anode. There was revealed essential role of formation of a virtual cathode and a potential well corresponding thereto in the processes of collisional DD synthesis in the interelectrode space. In this work, we have obtained as a result of an experiment and discussed the neutron yield at the very initial stage of the discharge, when the beam of auto-electrons just starts to irradiate the non-ideal surface of the deuterium-loaded Pd anode.

  3. The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial

    Directory of Open Access Journals (Sweden)

    Andrea A. Howard

    2016-06-01

    Full Text Available Background: Initiating antiretroviral therapy (ART early during tuberculosis (TB treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective: The Start TB Patients on ART and Retain on Treatment (START Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design: Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center. The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6–9 months. Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete

  4. ST-segment resolution with bivalirudin versus heparin and routine glycoprotein IIb/IIIa inhibitors started in the ambulance in ST-segment elevation myocardial infarction patients transported for primary percutaneous coronary intervention: The EUROMAX ST-segment resolution substudy.

    Science.gov (United States)

    Van't Hof, Arnoud; Giannini, Francesco; Ten Berg, Jurrien; Tolsma, Rudolf; Clemmensen, Peter; Bernstein, Debra; Coste, Pierre; Goldstein, Patrick; Zeymer, Uwe; Hamm, Christian; Deliargyris, Efthymios; Steg, Philippe G

    2017-08-01

    Myocardial reperfusion after primary percutaneous coronary intervention (PCI) can be assessed by the extent of post-procedural ST-segment resolution. The European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) trial compared pre-hospital bivalirudin and pre-hospital heparin or enoxaparin with or without GPIIb/IIIa inhibitors (GPIs) in primary PCI. This nested substudy was performed in centres routinely using pre-hospital GPI in order to compare the impact of randomized treatments on ST-resolution after primary PCI. Residual cumulative ST-segment deviation on the single one hour post-procedure electrocardiogram (ECG) was assessed by an independent core laboratory and was the primary endpoint. It was calculated that 762 evaluable patients were needed to show non-inferiority (85% power, alpha 2.5%) between randomized treatments. A total of 871 participated with electrocardiographic data available in 824 patients (95%). Residual ST-segment deviation one hour after PCI was 3.8±4.9 mm versus 3.9±5.2 mm for bivalirudin and heparin+GPI, respectively ( p=0.0019 for non-inferiority). Overall, there were no differences between randomized treatments in any measures of ST-segment resolution either before or after the index procedure. Pre-hospital treatment with bivalirudin is non-inferior to pre-hospital heparin + GPI with regard to residual ST-segment deviation or ST-segment resolution, reflecting comparable myocardial reperfusion with the two strategies.

  5. PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma.

    Science.gov (United States)

    Gaiser, Maria Rita; Bongiorno, Michelle; Brownell, Isaac

    2018-04-01

    Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that lacks durable responses to traditional chemotherapy. Areas covered: After MCC was shown to be an immunogenic tumor, small trials revealed high objective response rates to PD-1/PD-L1 checkpoint inhibitors. The JAVELIN Merkel 200 (NCT02155647) trial tested the use of avelumab, a human IgG1 monoclonal antibody against PD-L1, in metastatic MCC. Avelumab recently became the first approved drug for metastatic MCC. Expert commentary: By conducting broad phase I studies assessing the safety of avelumab and a small phase II study demonstrating efficacy in this rare orphan tumor type, avelumab gained accelerated approval for the treatment of metastatic MCC. Additional studies are needed to determine how the antibody-dependent cellular cytotoxicity (ADCC) competent Fc region of avelumab contributes to disease control. Remaining questions: Longer follow-up will determine the durability of checkpoint blockade in controlling metastatic MCC. Additional studies will assess the utility and safety of adjuvant checkpoint blockade in patients with excised MCC. How to increase response rates by combining PD-1/PD-L1 blockade with other treatment approaches needs to be explored. In addition, treatment options for MCC patients who fail or do not respond to avelumab need to be identified.

  6. A Healthy Start Can Begin Now

    Science.gov (United States)

    A healthy pregnancy begins before you ever become pregnant. Give yourself the best chance for a healthy pregnancy and healthy baby before you start down the road to motherhood. If you smoke, now’s a great time to quit.

  7. The physics of tokamak start-up

    International Nuclear Information System (INIS)

    Mueller, D.

    2013-01-01

    Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases, inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. International Thermonuclear Experimental Reactor, the National Spherical Torus Experiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection, and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current

  8. Start small and build toward business intelligence.

    Science.gov (United States)

    Kirby, Sean; Robertson, Brian

    2009-01-01

    To use business intelligence effectively, healthcare organizations should start small, align organizationally, and leverage success. Organizations should determine which measures they need and how to present them. Organizations should reinvest savings to continually improve.

  9. Lean Start-up in Established Companies

    DEFF Research Database (Denmark)

    Goduscheit, René Chester

    2018-01-01

    Lean start-up is an emergent perspective on how entrepreneurs can bring new products and services to the market. This approach challenges the dominant role of lengthy business plans, linear product development processes, and seeking complete overview of the potential of the new products....../services before market launch. Instead it suggests that start-ups could benefit from a ‘minimum-viable product’ approach where products and services are launched when they contain critical features. The emphasis in the lean start-up approach is on business models rather than the elaborate business plan...... at the companies (strategy meetings, development workshops etc.). The aim is to shed light on the implications for companies that seek to employ lean start-up. These implications will be aimed at aspects like innovation management, organizational structure, customer relations etc....

  10. Characterization of PD-1 upregulation on tumor-infiltrating lymphocytes in human and murine gliomas and preclinical therapeutic blockade.

    Science.gov (United States)

    Dejaegher, Joost; Verschuere, Tina; Vercalsteren, Ellen; Boon, Louis; Cremer, Jonathan; Sciot, Raf; Van Gool, Stefaan W; De Vleeschouwer, Steven

    2017-11-01

    Blockade of the immune checkpoint molecule programmed-cell-death-protein-1 (PD-1) yielded promising results in several cancers. To understand the therapeutic potential in human gliomas, quantitative data describing the expression of PD-1 are essential. Moreover, due the immune-specialized region of the brain in which gliomas arise, differences between tumor-infiltrating and circulating lymphocytes should be acknowledged. In this study we have used flow cytometry to quantify PD-1 expression on tumor-infiltrating T cells of 25 freshly resected glioma cell suspensions (10 newly and 5 relapsed glioblastoma, 10 lower grade gliomas) and simultaneously isolated circulating T cells. A strong upregulation of PD-1 expression in the tumor microenvironment compared to the blood circulation was seen in all glioma patients. Additionally, circulating T cells were isolated from 15 age-matched healthy volunteers, but no differences in PD-1 expression were found compared to glioma patients. In the murine GL261 malignant glioma model, there was a similar upregulation of PD-1 on brain-infiltrating lymphocytes. Using a monoclonal PD-1 blocking antibody, we found a marked prolonged survival with 55% of mice reaching long-term survival. Analysis of brain-infiltrating cells 21 days after GL261 tumor implantation showed a shift in infiltrating lymphocyte subgroups with increased CD8+ T cells and decreased regulatory T cells. Together, our results suggest an important role of PD-1 in glioma-induced immune escape, and provide translational evidence for the use of PD-1 blocking antibodies in human malignant gliomas. © 2017 UICC.

  11. Potential of Diffusion Tensor Imaging and Relaxometry for the Detection of Specific Pathological Alterations in Parkinson's Disease (PD.

    Directory of Open Access Journals (Sweden)

    Regina Esterhammer

    Full Text Available The purpose of the present study was to evaluate the potential of multimodal MR imaging including mean diffusivity (MD, fractional anisotropy (FA, relaxation rates R2 and R2* to detect disease specific alterations in Parkinson's Disease (PD. We enrolled 82 PD patients (PD-all with varying disease durations (≤5 years: PD≤5, n = 43; >5 years: PD>5, n = 39 and 38 matched healthy controls (HC, receiving diffusion tensor imaging as well as R2 and R2* relaxometry calculated from multi-echo T2*-weighted and dual-echo TSE imaging, respectively. ROIs were drawn to delineate caudate nucleus (CN, putamen (PU, globus pallidus (GP and substantia nigra (SN on the co-registered maps. The SN was divided in 3 descending levels (SL 1-3. The most significant parameters were used for a flexible discrimination analysis (FDA in a training collective consisting of 25 randomized subjects from each group in order to predict the classification of remaining subjects. PD-all showed significant increases in MD, R2 and R2* within SN and its subregions as well as in MD and R2* within different basal ganglia regions. Compared to the HC group, the PD≤5 and the PD>5 group showed significant MD increases within the SN and its lower two subregions, while the PD≤5 group exhibited significant increases in R2 and R2* within SN and its subregions, and tended to elevation within the basal ganglia. The PD>5 group had significantly increased MD in PU and GP, whereas the PD≤5 group presented normal MD within the basal ganglia. FDA achieved right classification in 84% of study participants. Micro-structural damage affects primarily the SN of PD patients and in later disease stages the basal ganglia. Iron contents of PU, GP and SN are increased at early disease stages of PD.

  12. Cerebral Activations Related to Ballistic, Stepwise Interrupted and Gradually Modulated Movements in Parkinson Patients

    Science.gov (United States)

    Toxopeus, Carolien M.; Maurits, Natasha M.; Valsan, Gopal; Conway, Bernard A.; Leenders, Klaus L.; de Jong, Bauke M.

    2012-01-01

    Patients with Parkinson’s disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced

  13. Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in Parkinson patients.

    Directory of Open Access Journals (Sweden)

    Carolien M Toxopeus

    Full Text Available Patients with Parkinson's disease (PD experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12 and healthy subjects (N = 18. In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN and premotor activations while inhibition was dominated by subthalamic nucleus (STN and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account

  14. The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study

    Directory of Open Access Journals (Sweden)

    Corbett Alastair

    2008-11-01

    Full Text Available Abstract Background We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2-related Parkinson's disease (PD in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S, is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. Methods A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. Results Thirty-one out of 509 families with multiple cases of PD (6.1% were found to have 58 LRRK2 mutation carriers (6.4%. Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. Conclusion Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility

  15. 76 FR 37174 - Capital Investment Program-New Starts and Small Starts Program Funds

    Science.gov (United States)

    2011-06-24

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Capital Investment Program--New Starts... apportionment of the FY 2011 Capital Investment (New Starts and Small Starts) program funds. The funds will be... FY 2011, $1,596,800,000 was appropriated for the Capital Investments Grant Account, which includes...

  16. START: the creation of a spherical tokamak

    International Nuclear Information System (INIS)

    Sykes, Alan

    1992-01-01

    The START (Small Tight Aspect Ratio Tokamak) plasma fusion experiment is now operational at AEA Fusion's Culham Laboratory. It is the world's first experiment to explore an extreme limit of the tokamak - the Spherical Tokamak - which theoretical studies predict may have substantial advantages in the search for economic fusion power. The Head of the START project, describes the concept, some of the initial experimental results and the possibility of developing a spherical tokamak power reactor. (author)

  17. Mitochondrial Calcium Dysregulation Contributes to Dendrite Degeneration Mediated by PD/LBD-Associated LRRK2 Mutants.

    Science.gov (United States)

    Verma, Manish; Callio, Jason; Otero, P Anthony; Sekler, Israel; Wills, Zachary P; Chu, Charleen T

    2017-11-15

    Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear. Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs before the well-characterized phenotype of dendritic shortening. As mitochondria play a major role in the rapid buffering of cytosolic calcium, we hypothesized that altered mitochondrial calcium handling contributes to dendritic retraction elicited by the LRRK2-G2019S and -R1441C mutations. In primary mouse cortical neurons, we observed increased depolarization-induced mitochondrial calcium uptake. We found that expression of mutant LRRK2 elicited transcriptional upregulation of the mitochondrial calcium uniporter (MCU) and the mitochondrial calcium uptake 1 protein (MICU1) with no change in levels of the mitochondrial calcium antiporter NCLX. Elevated MCU and MICU1 were also observed in LRRK2-mutated patient fibroblasts, along with increased mitochondrial calcium uptake, and in postmortem brains of sporadic PD/PDD patients of both sexes. Transcriptional upregulation of MCU and MICU1 was caused by activation of the ERK1/2 (MAPK3/1) pathway. Inhibiting ERK1/2 conferred protection against mutant LRRK2-induced neurite shortening. Pharmacological inhibitors or RNAi knockdown of MCU attenuated mitochondrial calcium uptake and dendritic/neuritic shortening elicited by mutant LRRK2, whereas expression of a constitutively active mutant of NCLX that enhances calcium export from mitochondria was neuroprotective. These data suggest that an increased susceptibility to mitochondrial calcium dysregulation contributes to dendritic injury in mutant LRRK2 pathogenesis. SIGNIFICANCE STATEMENT Cognitive dysfunction and dementia are

  18. The Significance of the PD-L1 Expression in Non-Small-Cell Lung Cancer: Trenchant Double Swords as Predictive and Prognostic Markers.

    Science.gov (United States)

    Takada, Kazuki; Toyokawa, Gouji; Shoji, Fumihiro; Okamoto, Tatsuro; Maehara, Yoshihiko

    2018-03-01

    Lung cancer is the leading cause of death due to cancer worldwide. Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes. Despite advances in such therapies, the prognosis of patients with NSCLC without driver oncogene mutations remains poor. Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC. The PD-L1 expression on the surface of tumor cells has emerged as a potential biomarker for predicting responses to immunotherapy and prognosis after surgery in NSCLC. However, the utility of PD-L1 expression as a predictive and prognostic biomarker remains controversial because of the existence of various PD-L1 antibodies, scoring systems, and positivity cutoffs. In this review, we summarize the data from representative clinical trials of PD-1/PD-L1 immune checkpoint inhibitors in NSCLC and previous reports on the association between PD-L1 expression and clinical outcomes in patients with NSCLC. Furthermore, we discuss the future perspectives of immunotherapy and immune checkpoint factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Coentrão Luis

    2012-08-01

    Full Text Available Abstract Background Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD over hemodialysis (HD, the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation. Methods A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC or a functional arteriovenous fistula (HD-AVF in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42. All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC. Results Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (pp = 0.017 and cardiovascular disease (p = 0.020. Overall, HD-TCC patients were more likely to have clinical visits (p = 0.069, emergency room visits (ppvs. 0.93 vs. 0.64, per patient-year; pvs. 0.07 vs. 0.14, per patient-year; p = 0.034 than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (pp = 0.024. Conclusion Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.

  20. QUALITY OF LIFE AND NUTRITIONAL STATUS ASSESSED BY MULTIFREQUENCY BIOIMPEDANCE SPECTROSCOPY IN HEMODIALYSIS VERSUS PERITONEAL DIALYSIS PATIENTS

    Directory of Open Access Journals (Sweden)

    Somchai Yongsiri

    2012-06-01

    In conclusion, quality of life and Nutritional status were not difference between PD and HD patients. PD patients had more over hydration and ECW to ICW ratio as assessed by bioimpedance spectroscopy.

  1. Whole-brain diffusion-tensor changes in parkinsonian patients with impulse control disorders.

    Science.gov (United States)

    Yoo, Hye Bin; Lee, Jee-Young; Lee, Jae Sung; Kang, Hyejin; Kim, Yu Kyeong; Song, In Chan; Lee, Dong Soo; Jeon, Beom Seok

    2015-01-01

    The aim of this study was to determine the changes in diffusion-tensor images associated with medication-related impulse control disorder (ICD) in Parkinson's disease (PD) patients undergoing chronic dopamine-replacement therapy. Nineteen PD patients, comprising 10 with ICD (PD-ICD) and 9 without ICD (PD-nonICD), and 18 age-matched healthy controls (HCs) with no cognitive or other psychiatric disorders were analyzed. All subjects underwent 3-T magnetic resonance diffusion-tensor imaging. For all PD patients, clinical data on PD duration, antiparkinsonian medication dosages, Unified Parkinson's Disease Rating Scale and Mini-Mental State Examination were collected. Whole-brain voxel-based measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed. In comparison with HCs, the PD-nonICD subjects had low FA at the bilateral orbitofrontal areas. While the PD-ICD subjects exhibited no such difference, their FA was significantly elevated at the anterior corpus callosum. Analysis of FA between the two PD groups revealed that FA in the anterior corpus callosum, right internal capsule posterior limbs, right posterior cingulum, and right thalamic radiations were significantly higher (corrected p<0.05) in the PD-ICD than in the PD-nonICD patients. MD did not differ between the PD-ICD and PD-nonICD groups in any brain regions. The PD-ICD patients appear to have relatively preserved white-matter integrity in the regions involved in reward-related behaviors compared to PD-nonICD patients. Further investigation is required to determine whether the difference in FA between PD-ICD and PD-nonICD patients reflects microstructural differences in the pathological progression of PD or is secondary to ICD.

  2. A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma.

    Science.gov (United States)

    Maekawa, Naoya; Konnai, Satoru; Takagi, Satoshi; Kagawa, Yumiko; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Deguchi, Tatsuya; Nakajima, Chie; Kato, Yukinari; Yamamoto, Keiichi; Uemura, Hidetoshi; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

    2017-08-21

    Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.

  3. CO tolerance of PdPt/C and PdPtRu/C anodes for PEMFC

    International Nuclear Information System (INIS)

    Garcia, Amanda C.; Paganin, Valdecir A.; Ticianelli, Edson A.

    2008-01-01

    The performance of H 2 /O 2 proton exchange membrane fuel cells (PEMFCs) fed with CO-contaminated hydrogen was investigated for anodes with PdPt/C and PdPtRu/C electrocatalysts. The physicochemical properties of the catalysts were characterized by energy dispersive X-ray (EDX) analyses, X-ray diffraction (XRD) and 'in situ' X-ray absorption near edge structure (XANES). Experiments were conducted in electrochemical half and single cells by cyclic voltammetry (CV) and I-V polarization measurements, while DEMS was employed to verify the formation of CO 2 at the PEMFC anode outlet. A quite high performance was achieved for the PEMFC fed with H 2 + 100 ppm CO with the PdPt/C and PdPtRu/C anodes containing 0.4 mg metal cm -2 , with the cell presenting potential losses below 200 mV at 1 A cm -2 , with respect to the system fed with pure H 2 . For the PdPt/C catalysts no CO 2 formation was seen at the PEMFC anode outlet, indicating that the CO tolerance is improved due to the existence of more free surface sites for H 2 electrooxidation, probably due to a lower Pd-CO interaction compared to pure Pd or Pt. For PdPtRu/C the CO tolerance may also have a contribution from the bifunctional mechanism, as shown by the presence of CO 2 in the PEMFC anode outlet

  4. Progress of PD-1/PD-L1 Inhibitors in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Zhansheng JIANG

    2017-02-01

    Full Text Available Pembrolizumab, an inhibitor target programmed death 1 (PD-1, was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC. It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1 inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS with single pembrolizumab in first line was nearly 1 year (10.3 months, the hazard ratio for death fell by 40%. Overall survival (OS was more or less 1 year with single drug pembrolizumab, nivolumab and atezolizumab for second line therapy. PD-L1 expression was a predictor of PD-1/PD-L1 inhibitors. The positive rate of PD-L1 (more than 1% in advanced NSCLC was about 60% with little difference between the tissue types. However, there was no gold standard test of PD-L1 expression.

  5. Measurement of benzenethiol adsorption to nanostructured Pt, Pd, and PtPd films using Raman spectroelectrochemistry.

    Science.gov (United States)

    Pomfret, Michael B; Pietron, Jeremy J; Owrutsky, Jeffrey C

    2010-05-04

    Raman spectroscopy and electrochemical methods were used to study the behavior of the model adsorbate benzenethiol (BT) on nanostructured Pt, Pd, and PtPd electrodes as a function of applied potential. Benzenethiol adsorbs out of ethanolic solutions as the corresponding thiolate, and voltammetric stripping data reveal that BT is oxidatively removed from all of the nanostructured metals upon repeated oxidative and reductive cycling. Oxidative stripping potentials for BT increase in the order Pt oxidizing potentials via cleavage of the Pt-S bond. In contrast, on nanoscale Pd and PtPd, BT is irreversibly lost due to cleavage of BT C-S bonds at oxidizing potentials, which leaves adsorbed sulfur oxides on Pd and PtPd films and effects the desulfurization of BT. While Pd and PtPd films are less sulfur-resistant than Pt films, palladium oxides, which form at higher potentials than Pt oxides, oxidatively desulfurize BT. In situ spectroelectrochemical Raman spectroscopy provides real-time, chemically specific information that complements the cyclic voltammetric data. The combination of these techniques affords a powerful and convenient method for guiding the development of sulfur-tolerant PEMFC catalysts.

  6. Preparation of supported Au–Pd and Cu–Pd by the combined strong ...

    Indian Academy of Sciences (India)

    BOONTIDA PONGTHAWORNSAKUN

    2017-10-25

    Oct 25, 2017 ... Bimetallic catalyst; Au–Pd/TiO2; Cu–Pd/TiO2; strong electrostatic adsorption; electroless deposition .... The liquid samples .... composition and gas mixture product at the outlet of reactor ... the TiO2 support (no change in the deposition curve of. TiO2). ..... TrimmDL1980In Design of Industrial Catalysts (Ams-.

  7. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

    2018-03-01

    Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

  8. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4

    Directory of Open Access Journals (Sweden)

    Shinji Yamada

    2018-03-01

    Full Text Available Programmed cell death-ligand 1 (PD-L1, which is a ligand of programmed cell death-1 (PD-1, is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1 expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb, L1Mab-4 (IgG2b, kappa, using cell-based immunization and screening (CBIS method and investigated hPD-L1 expression in oral cancers. L1Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 in flow cytometry and stained oral cancers in a membrane-staining pattern. L1Mab-4 stained 106/150 (70.7% of oral squamous cell carcinomas, indicating the very high sensitivity of L1Mab-4. These results indicate that L1Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers. Keywords: Programmed cell death-ligand 1, Monoclonal antibody, Oral cancer

  9. The immune checkpoint regulator PD-L1 is a specific target for naturally occurring CD4(+) T cells

    DEFF Research Database (Denmark)

    Munir, Shamaila; Andersen, Gitte Holmen; Svane, Inge Marie

    2013-01-01

    Programmed cell death 1 ligand 1 (PD-L1) is an important regulator of T-cell responses and may consequently limit anticancer immunity. We have recently identified PD-L1-specific, cytotoxic CD8(+) T cells. In the present study, we develop these findings and report that CD4(+) helper T cells...... spontaneously recognize PD-L1. We examined the locality of a previously identified HLA-A*0201-restricted PD-L1-epitope for the presence of possible CD4(+) T-cell epitopes. Thus, we identified naturally occurring PD-L1-specific CD4(+) T cells among the peripheral blood lymphocytes of cancer patients...... and - to lesser extents - healthy donors, by means of ELISPOT assays. PD-L1-specific CD4(+) T cells appeared to be TH17 cells exhibiting an effector T-cell cytokine profile. Hence, PD-L1-specific CD4(+) T cells released interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin-17 (IL-17) in response...

  10. Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica.

    Directory of Open Access Journals (Sweden)

    Sha Zhou

    2016-10-01

    Full Text Available More than 220 million people worldwide are chronically infected with schistosomes, causing severe disease or even death. The major pathological damage occurring in schistosomiasis is attributable to the granulomatous inflammatory response and liver fibrosis induced by schistosome eggs. The inflammatory response is tightly controlled and parallels immunosuppressive regulation, constantly maintaining immune homeostasis and limiting excessive immunopathologic damage in important host organs. It is well known that the activation of programmed death 1 (PD-1 signaling causes a significant suppression of T cell function. However, the roles of PD-1 signaling in modulating CD4+ T cell responses and immunopathology during schistosome infection, have yet to be defined.Here, we show that PD-1 is upregulated in CD4+ T cells in Schistosoma japonicum (S. japonicum-infected patients. We also show the upregulation of PD-1 expression in CD4+ T cells in the spleens, mesenteric lymph nodes, and livers of mice with S. japonicum infection. Finally, we found that the blockade of PD-1 signaling enhanced CD4+ T helper 2 (Th2 cell responses and led to more severe liver immunopathology in mice with S. japonicum infection, without a reduction of egg production or deposition in the host liver.Overall, our study suggests that PD-1 signaling is specifically induced to control Th2-associated inflammatory responses during schistosome infection and is beneficial to the development of PD-1-based control of liver immunopathology.

  11. Domain structures and magnetization reversal in Co/Pd and CoFeB/Pd multilayers

    Energy Technology Data Exchange (ETDEWEB)

    Sbiaa, R., E-mail: rachid@squ.edu.om [Department of Physics, Sultan Qaboos University, P.O. Box 36, PC 123 (Oman); Ranjbar, M. [Physics Department, University of Gothenburg, 412 96 Gothenburg (Sweden); Åkerman, J. [Physics Department, University of Gothenburg, 412 96 Gothenburg (Sweden); Materials Physics, School of ICT, Royal Institute of Technology (KTH), 164 40 Kista (Sweden)

    2015-05-07

    Domain structures and magnetization reversal of (Co/Pd) and (CoFeB/Pd) multilayers with 7 and 14 repeats were investigated. The Co-based multilayers show much larger coercivities, a better squareness, and a sharper magnetization switching than CoFeB-based multilayers. From magnetic force microscopy observations, both structures show strong reduction in domains size as the number of repeats increases but the magnetic domains for Co-based multilayers are more than one order of magnitude larger than for CoFeB-based multilayers. By imaging domains at different times, breaks in the (CoFeB/Pd) multilayer stripes were observed within only few hours, while no change could be seen for (Co/Pd) multilayers. Although CoFeB single layers are suitable for magnetoresistive devices due to their large spin polarization and low damping constants, their lamination with Pd suffers mainly from thermal instability.

  12. The Concordance between Patients' Renal Replacement Therapy Choice and Definitive Modality: Is It a Utopia?

    Science.gov (United States)

    Prieto-Velasco, Mario; Quiros, Pedro; Remon, Cesar

    2015-01-01

    It is desirable for patients to play active roles in the choice of renal replacement therapy (RRT). Patient decision aid tools (PDAs) have been developed to allow the patients to choose the option best suited to their individual needs. An observational, prospective registry was conducted in 26 Spanish hospitals between September 2010 and May 2012. The results of the patients' choice and the definitive RRT modality were registered through the progressive implementation of an Education Process (EP) with PDAs designed to help Chronic Kidney Disease (CKD) patients choose RRT. Patients included in this study: 1044. Of these, 569 patients used PDAs and had made a definitive choice by the end of registration. A total of 88.4% of patients chose dialysis [43% hemodialysis (HD) and 45% peritoneal dialysis (PD)] 3.2% preemptive living-donor transplant (TX), and 8.4% conservative treatment (CT). A total of 399 patients began RRT during this period. The distribution was 93.4% dialysis (53.6% HD; 40% PD), 1.3% preemptive TX and 5.3% CT. The patients who followed the EP changed their mind significantly less often [kappa value of 0.91 (95% CI, 0.86-0.95)] than those who did not follow it, despite starting unplanned treatment [kappa value of 0.85 (95% CI, 0.75-0.95]. A higher agreement between the final choice and a definitive treatment was achieved by the EP and planned patients [kappa value of 0.93 (95% CI, 0.89-0.98)]. Those who did not go through the EP had a much lower index of choosing PD and changed their decision more frequently when starting definitive treatment [kappa value of 0.73 (95% CI, 0.55-0.91)]. Free choice, assisted by PDAs, leads to a 50/50 distribution of PD and HD choice and an increase in TX choice. The use of PDAs, even with an unplanned start, achieved a high level of concordance between the chosen and definitive modality.

  13. Magnetic characteristics of CoPd and FePd antidot arrays on nanoperforated Al2O3 templates

    Science.gov (United States)

    Maximenko, A.; Fedotova, J.; Marszałek, M.; Zarzycki, A.; Zabila, Y.

    2016-02-01

    Hard magnetic antidot arrays show promising results in context of designing of percolated perpendicular media. In this work the technology of magnetic FePd and CoPd antidot arrays fabrication is presented and correlation between surface morphology, structure and magnetic properties is discussed. CoPd and FePd antidot arrays were fabricated by deposition of Co/Pd and Fe/Pd multilayers (MLs) on porous anodic aluminum oxide templates with bowl-shape cell structure with inclined intercellular regions. FePd ordered L10 structure was obtained by successive vacuum annealing at elevated temperatures (530 °C) and confirmed by XRD analysis. Systematic analysis of magnetization curves evidenced perpendicular magnetic anisotropy of CoPd antidot arrays, while FePd antidot arrays revealed isotropic magnetic anisotropy with increased out-of-plane magnetic contribution. MFM images of antidots showed more complicated contrast, with alternating magnetic dots oriented parallel and antiparallel to tip magnetization moment.

  14. Generation and oxidation of aerosol deposited PdAg nanoparticles

    Science.gov (United States)

    Blomberg, S.; Gustafson, J.; Martin, N. M.; Messing, M. E.; Deppert, K.; Liu, Z.; Chang, R.; Fernandes, V. R.; Borg, A.; Grönbeck, H.; Lundgren, E.

    2013-10-01

    PdAg nanoparticles with a diameter of 10 nm have been generated by an aerosol particle method, and supported on a silica substrate. By using a combination of X-ray Energy Dispersive Spectroscopy and X-ray Photoelectron Spectroscopy it is shown that the size distribution of the particles is narrow and that the two metals form an alloy with a mixture of 75% Pd and 25% Ag. Under oxidizing conditions, Pd is found to segregate to the surface and a thin PdO like oxide is formed similar to the surface oxide previously reported on extended PdAg and pure Pd surfaces.

  15. PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma.

    Science.gov (United States)

    Melaiu, Ombretta; Mina, Marco; Chierici, Marco; Boldrini, Renata; Jurman, Giuseppe; Romania, Paolo; D'Alicandro, Valerio; Benedetti, Maria C; Castellano, Aurora; Liu, Tao; Furlanello, Cesare; Locatelli, Franco; Fruci, Doriana

    2017-08-01

    Purpose: This study sought to evaluate the expression of programmed cell death-ligand-1 (PD-L1) and HLA class I on neuroblastoma cells and programmed cell death-1 (PD-1) and lymphocyte activation gene 3 (LAG3) on tumor-infiltrating lymphocytes to better define patient risk stratification and understand whether this tumor may benefit from therapies targeting immune checkpoint molecules. Experimental Design: In situ IHC staining for PD-L1, HLA class I, PD-1, and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T-cell density and correlated with clinical outcome. Surface expression of PD-L1 was evaluated by flow cytometry and IHC in neuroblastoma cell lines and tumors genetically and/or pharmacologically inhibited for MYC and MYCN. A dataset of 477 human primary neuroblastomas from GEO and ArrayExpress databases was explored for PD-L1, MYC, and MYCN correlation. Results: Multivariate Cox regression analysis demonstrated that the combination of PD-L1 and HLA class I tumor cell density is a prognostic biomarker for predicting overall survival in neuroblastoma patients ( P = 0.0448). MYC and MYCN control the expression of PD-L1 in neuroblastoma cells both in vitro and in vivo Consistently, abundance of PD-L1 transcript correlates with MYC expression in primary neuroblastoma. Conclusions: The combination of PD-L1 and HLA class I represents a novel prognostic biomarker for neuroblastoma. Pharmacologic inhibition of MYCN and MYC may be exploited to target PD-L1 and restore an efficient antitumor immunity in high-risk neuroblastoma. Clin Cancer Res; 23(15); 4462-72. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. The impact of dry-land sprint start training on the short track speed skating start.

    Science.gov (United States)

    Haug, William B; Drinkwater, Eric J; Cicero, Nicholas J; Barthell, J Anthony; Chapman, Dale W

    2017-05-05

    This investigation sought to determine the effects of dry-land sprint start training on short track speed skating (STSS) start performance. Nine highly trained short track athletes completed a control period of normal STSS training followed by a four-week training intervention. Before and after the control and intervention periods, athletes performed three electronically timed dry-land and on-ice 14.43 m maximal sprint start efforts. The intervention consisted of two sprint sessions per week consisting of nine electronically timed 14.43 m dry-land sprint starts in addition to normal STSS training. The control period resulted in no substantial change in on-ice start performance (Mean Δ: -0.01 s, 95% Confidence Limits (CL): -0.08 to 0.05 s; Effect Size (ES): -0.05; Trivial) however, a small change was observed in dry-land start performance (Mean Δ: -0.07 s, 95% CL: -0.13 to -0.02 s; ES: -0.49). Following brief specific dry-land sprint start training a small improvement was observed in both on-ice (Mean Δ: -0.07 s, 95% CL: -0.13 to -0.01 s; ES: -0.33) and dry-land (Mean Δ: -0.04 s, 95% CL: -0.09 to 0.00 s; ES: -0.29) start performance. This investigation suggests STSS start performance can be improved through a brief dry-land sprint start training program.

  17. Prognostic factors of motor impairment, disability, and quality of life in newly diagnosed PD

    NARCIS (Netherlands)

    Velseboer, D.C.; Broeders, M.; Post, B.; Van Geloven, N.; Speelman, J.D.; Schmand, B.A.; Haan, R.J. de; Bie, R.M. de; et al.,

    2013-01-01

    OBJECTIVE: In Parkinson disease (PD), the rate of clinical progression is highly variable. To date, there are conflicting findings concerning the prognostic factors influencing the rate of progression. Methodologic issues such as the use of selected patients from therapeutic trials, and short

  18. Satisfaction with care in peritoneal dialysis patients.

    Science.gov (United States)

    Kirchgessner, J; Perera-Chang, M; Klinkner, G; Soley, I; Marcelli, D; Arkossy, O; Stopper, A; Kimmel, P L

    2006-10-01

    Patient satisfaction is an important aspect of dialysis care, only recently evaluated in clinical studies. We developed a tool to assess peritoneal dialysis (PD) customer satisfaction, and sought to evaluate and validate the Customer Satisfaction Questionnaire (CSQ), quantifying PD patient satisfaction. The CSQ included questions regarding administrative issues, Delivery Service, PD Training, Handling Requests, and transportation. The study was performed using interviews in all Hungarian Fresenius Medical Care dialysis centers offering PD. CSQ results were compared with psychosocial measures to identify if patient satisfaction was associated with perception of social support and illness burden, or depression. We assessed CSQ internal consistency and validity. Factor analysis explored potential underlying dimensions of the CSQ. One hundred and thirty-three patients treated with PD for end-stage renal disease for more than 3 months were interviewed. The CSQ had high internal consistency. There was high patient satisfaction with customer service. PD patient satisfaction scores correlated with quality of life (QOL) and social support measures, but not with medical or demographic factors, or depressive affect. The CSQ is a reliable tool to assess PD customer satisfaction. PD patient satisfaction is associated with perception of QOL. Efforts to improve customer satisfaction may improve PD patients' quantity as well as QOL.

  19. Virtual Resting Pd/Pa From Coronary Angiography and Blood Flow Modelling: Diagnostic Performance Against Fractional Flow Reserve.

    Science.gov (United States)

    Papafaklis, Michail I; Muramatsu, Takashi; Ishibashi, Yuki; Bourantas, Christos V; Fotiadis, Dimitrios I; Brilakis, Emmanouil S; Garcia-Garcia, Héctor M; Escaned, Javier; Serruys, Patrick W; Michalis, Lampros K

    2018-03-01

    Fractional flow reserve (FFR) has been established as a useful diagnostic tool. The distal coronary pressure to aortic pressure (Pd/Pa) ratio at rest is a simpler physiologic index but also requires the use of the pressure wire, whereas recently proposed virtual functional indices derived from coronary imaging require complex blood flow modelling and/or are time-consuming. Our aim was to test the diagnostic performance of virtual resting Pd/Pa using routine angiographic images and a simple flow model. Three-dimensional quantitative coronary angiography (3D-QCA) was performed in 139 vessels (120 patients) with intermediate lesions assessed by FFR. The resting Pd/Pa for each lesion was assessed by computational fluid dynamics. The discriminatory power of virtual resting Pd/Pa against FFR (reference: ≤0.80) was high (area under the receiver operator characteristic curve [AUC]: 90.5% [95% CI: 85.4-95.6%]). Diagnostic accuracy, sensitivity and specificity for the optimal virtual resting Pd/Pa cut-off (≤0.94) were 84.9%, 90.4% and 81.6%, respectively. Virtual resting Pd/Pa demonstrated superior performance (pvirtual resting Pd/Pa and FFR (r=0.69, pVirtual resting Pd/Pa using routine angiographic data and a simple flow model provides fast functional assessment of coronary lesions without requiring the pressure-wire and hyperaemia induction. The high diagnostic performance of virtual resting Pd/Pa for predicting FFR shows promise for using this simple/fast virtual index in clinical practice. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  20. Guidelines for starting today's private practice

    Directory of Open Access Journals (Sweden)

    Schmitz ED

    2012-11-01

    Full Text Available No abstract available. Article truncated at 150 words. Starting a new practice may seem like a daunting task. The purpose of this article is to demystify the process of creating a new practice from the beginning. The cardinal rule is to keep costs low and not to outsource work that can easily be performed by any competent physician and staff. You do not need a manager, lawyer, business partner, coder or biller individually; you may be able to perform many of these services yourself. What you do need is a commitment to making your practice a success. Do not spend too much on your office space, furnishings or equipment. Start with the bare essentials. Immediately start applying to all insurance companies especially Medicare. Request an employer identification number. Set up a basic business banking account and submit the account number to the insurance companies you plan to work with. You can purchase an entire electronic healthcare record (EHR …

  1. Starting a business through a franchise

    Directory of Open Access Journals (Sweden)

    Dubravka Mahaček

    2013-12-01

    Full Text Available A business can be launched by establishing a new entity, purchasing an existing entity or through a franc - hise. There are certain prerequisites for starting a business, the most important ones being a quality idea and start-up capital. Potential start-up difficulties are inadequate financing, existing competition as well as the process of building your own market position. By purchasing an existing business some risks may be avoided and the opportunity for gaining profit may arise. Profitable operation is possible only if this business has up-to-date products and no outstanding liabilities. This paper discusses franchising business opportunities and the requisite investments and costs, which will bring success if they are accompanied by franchisee’s efforts. The paper aims to present the main characteristics of a franchise business, the necessary investment and the costs which arise in the process, as well as advantages, disadvantages and experiences with this kind of business

  2. Research nuclear reactor start-up simulator

    International Nuclear Information System (INIS)

    Sofo Haro, M.; Cantero, P.

    2009-01-01

    This work presents the design and FPGA implementation of a research nuclear reactor start-up simulator. Its aim is to generate a set of signals that allow replacing the neutron detector for stimulated signals, to feed the measurement electronic of the start-up channels, to check its operation, together with the start-up security logic. The simulator presented can be configured on three independent channels and adjust the shape of the output pulses. Furthermore, each channel can be configured in 'rate' mode, where you can specify the growth rate of the pulse frequency in %/s. Result and details of the implementation on FPGA of the different functional blocks are given. (author)

  3. Smart or Diverse Start-up Teams?

    DEFF Research Database (Denmark)

    Hoogendoorn, Sander; Parker, Simon C.; Van Praag, Mirjam

    2017-01-01

    This paper explores the relationship between cognitive abilities and team performance in a start-up setting. We argue that performance in this setting hinges on three tasks: opportunity recognition, problem solving, and implementation. We theorize that cognitive ability at the individual level has...... others can be assigned to tasks that impose a greater cognitive load (problem solving or opportunity recognition). We present the results of a field experiment in which 573 students in 49 teams started up and managed real companies. We ensured exogenous variation in—otherwise random—team composition...... by assigning students to teams based on their measured cognitive abilities. Each team performed a variety of tasks, often involving complex decision making. The key result of the experiment is that the performance of start-up teams first increases and then decreases with ability dispersion. Strikingly, average...

  4. PD-1 checkpoint inhibition: Toxicities and management.

    Science.gov (United States)

    Hahn, Andrew W; Gill, David M; Agarwal, Neeraj; Maughan, Benjamin L

    2017-12-01

    With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Then, we will discuss the specific management of the most common immune-mediated adverse events including colitis, hepatitis, pneumonitis, rash, endocrinopathies, nephritis, and neurologic toxicities. Immune-related adverse events are frequently treated with immunosuppressive medication such as steroids and mycofenolate mofetil. There are specific immune-related adverse events which are frequently seen by the treating oncologist from checkpoint inhibitors. It is essential to understand the recommended treatment options to minimize toxicity and mortality from this important class of anti-neoplastic therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Neurological Complications Associated With Anti-Programmed Death 1 (PD-1) Antibodies.

    Science.gov (United States)

    Kao, Justin C; Liao, Bing; Markovic, Svetomir N; Klein, Christopher J; Naddaf, Elie; Staff, Nathan P; Liewluck, Teerin; Hammack, Julie E; Sandroni, Paola; Finnes, Heidi; Mauermann, Michelle L

    2017-10-01

    Neurological complications are an increasingly recognized consequence of the use of anti-programmed death 1 (PD-1) antibodies in the treatment of solid-organ tumors, with an estimated frequency of 4.2%. To date, the clinical spectrum and optimum treatment approach are not established. To investigate the frequency, clinical spectrum, and optimum treatment approach to neurological complications associated with anti-PD-1 therapy. This single-center, retrospective cohort study was conducted from either September or December 2014 (the approval dates of the study drugs by the US Food and Drug Administration) to May 19, 2016. All patients receiving anti-PD-1 monoclonal antibodies were identified using the Mayo Cancer Pharmacy Database. Patients with development of neurological symptoms within 12 months of anti-PD-1 therapy were included. Patients with neurological complications directly attributable to metastatic disease or other concurrent cancer-related treatments were excluded. Clinical and pathological characteristics, time to development of neurological symptoms, and modified Rankin Scale (mRS) score. Among 347 patients treated with anti-PD1 monoclonal antibodies (pembrolizumab or nivolumab), 10 (2.9%) developed subacute onset of neurological complications. Seven patients were receiving pembrolizumab, and 3 patients were receiving nivolumab. The patients included 8 men and 2 women. Their median age was 71 years (age range, 31-78 years). Neurological complications occurred after a median of 5.5 (range, 1-20) cycles of anti-PD-1 inhibitors. Complications included myopathy (n = 2), varied neuropathies (n = 4), cerebellar ataxia (n = 1), autoimmune retinopathy (n = 1), bilateral internuclear ophthalmoplegia (n = 1), and headache (n = 1). Peripheral neuropathies included axonal and demyelinating polyradiculoneuropathies (n = 2), length-dependent neuropathies (n = 1), and asymmetric vasculitic neuropathy (n = 1). The time to maximum

  6. Anatomical correlates of cognitive functions in early Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Roberta Biundo

    Full Text Available Cognitive deficits may occur early in Parkinson's disease (PD but the extent of cortical involvement associated with cognitive dysfunction needs additional investigations. The aim of our study is to identify the anatomical pattern of cortical thickness alterations in patients with early stage PD and its relationship with cognitive disability.We recruited 29 PD patients and 21 healthy controls. All PD patients performed an extensive neuropsychological examination and 14 were diagnosed with mild cognitive impairment (PD-MCI. Surface-based cortical thickness analysis was applied to investigate the topographical distribution of cortical and subcortical alterations in early PD compared with controls and to assess the relationship between cognition and regional cortical changes in PD-MCI.Overall PD patients showed focal cortical (occipital-parietal areas, orbito-frontal and olfactory areas and subcortical thinning when compared with controls. PD-MCI showed a wide spectrum of cognitive deficits and related significant regional thickening in the right parietal-frontal as well as in the left temporal-occipital areas.Our results confirm the presence of changes in grey matter thickness at relatively early PD stage and support previous studies showing thinning and atrophy in the neocortex and subcortical regions. Relative cortical thickening in PD-MCI may instead express compensatory neuroplasticity. Brain reserve mechanisms might first modulate cognitive decline during the initial stages of PD.

  7. Early post-treatment pseudo-progression amongst glioblastoma multiforme patients treated with radiotherapy and temozolomide: a retrospective analysis

    International Nuclear Information System (INIS)

    Gunjur, Ashray; Lau, Eddie; Taouk, Yamna; Ryan, Gail

    2011-01-01

    To evaluate the incidence and impact of early post-chemoradiation (cRT) 'pseudoprogression' (PsPD) amongst glioblastoma multiforme (GBM) patients treated with the current standard of care – 60 Gy conformal radiotherapy with concurrent low-dose temozolomide, followed by six cycles of high-dose temozolomide (the 'Stupp protocol'). Clinical notes and radiology reports for GBM patients treated as per the Stupp protocol were reviewed. PsPD was defined as apparent radiological progression on the first post-cRT scan, with further imaging within 3 months being stable or improving, while true early progression (ePD) was confirmed by continued progression in the subsequent 3 months following the first post-cRT scan. Of the 68 patients evaluated, 14 (21%) and 27 (40%) experienced PsPD and ePD, respectively; 3/14 (21%) patients experiencing PsPD and 14/27(52%), ePD were symptomatic for progression on first post-cRT follow-up (P = 0.096 for difference). Median survival for patients with ePD, PsPD and neither were 10.4, 27.4 and 13.0 months, respectively (P = 0.003 for ePD vs. PsPD, P = 0.19 for neither vs. PsPD groups). These data confirm a significant incidence of PsPD in post-cRT GBM patients, associated with improved median survival compared with those with neither ePD nor PsPD (not statistically significant). It appears likely that PsPD actually represents tumour response, conflicting with the traditional notion that increase in lesion size on contrast-enhanced imaging represents disease progression. Early post-cRT imaging should thus be interpreted with caution. Accompanying clinical symptoms are more commonly associated with ePD, but do not reliably distinguish PsPD from ePD.

  8. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1 Virus Impairs the Human T Cell Response

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    2013-01-01

    Full Text Available PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1pdm09, and its effects on the T cell response have not been widely explored. We found that A(H1N1pdm09 virus induced PD-L1 expression on human dendritic cells (DCs and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1pdm09 virus.

  9. Two-Man Bobsled Push Start Analysis

    Directory of Open Access Journals (Sweden)

    Lopes Alexandre Dias

    2016-04-01

    Full Text Available The importance of push start times on bobsled performance was evidenced by some studies, but at this moment there is no article to the authors’ knowledge that describes the bobsled push start. Thus, the objectives of this study were to describe the two-man bobsled push start, analyze the differences between teams, and estimate the most important variable analyzed. We hypothesized that the pilot and brakeman athletes’ movement patterns during a bobsled pushing start can be described. The images used in this study were obtained during the men’s two-man XIV World Championship of Bobsled (2004. Fifteen best teams participating in the championship were recorded, and four start runs for each team were analyzed. The videos were captured by two digital video cameras. The pilot athletes were analyzed during the moment that they touched the lateral push bar of the sled, and the brakemen were analyzed during the first take-off and first landing. The teams were pooled in three groups of five teams using the final ranking of pushing time. We concluded that there was a distinct pattern movement for pilots and brakemen. The initial position of the majority of the pilots was localized slightly behind the bar. After touching the lateral bar, the pilots remained in a semi-squat position, pushing the sled forward in a pattern of marching movement. All brakemen used the board attached to the track as a support for both feet at the start. The brakeman gave the greatest contribution to break the inertia of the sled. There was no significant difference of movement between the three groups analyzed for the pilot and the brakeman.

  10. Using gastrocnemius sEMG and plasma α-synuclein for the prediction of freezing of gait in Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Xiao-Ying Wang

    Full Text Available Freezing of gait (FOG is a complicated gait disturbance in Parkinson's disease (PD and a relevant subclinical predictor algorithm is lacking. The main purpose of this study is to explore the potential value of surface electromyograph (sEMG and plasma α-synuclein levels as predictors of the FOG seen in PD. 21 PD patients and 15 normal controls were recruited. Motor function was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS and Freezing of gait questionnaire (FOG-Q. Simultaneously, gait analysis was also performed using VICON capture system in PD patients and sEMG data was recorded as well. Total plasma α-synuclein was quantitatively assessed by Luminex assay in all participants. Recruited PD patients were classified into two groups: PD patients with FOG (PD+FOG and without FOG (PD-FOG, based on clinical manifestation, the results of the FOG-Q and VICON capture system. PD+FOG patients displayed higher FOG-Q scores, decreased walking speed, smaller step length, smaller stride length and prolonged double support time compared to the PD-FOG in the gait trial. sEMG data indicated that gastrocnemius activity in PD+FOG patients was significantly reduced compared to PD-FOG patients. In addition, plasma α-synuclein levels were significantly decreased in the PD+FOG group compared to control group; however, no significant difference was found between the PD+FOG and PD-FOG groups. Our study revealed that gastrocnemius sEMG could be used to evaluate freezing gait in PD patients, while plasma α-synuclein might discriminate freezing of gait in PD patients from normal control, though no difference was found between the PD+FOG and PD-FOG groups.

  11. A case of severe encephalitis while on PD-1 immunotherapy for recurrent clear cell ovarian cancer

    Directory of Open Access Journals (Sweden)

    Morgan Burke

    2018-05-01

    Full Text Available Recurrent clear cell ovarian carcinoma is a difficult to treat condition and early trial data has suggested a possible role for immune checkpoint inhibitors. Nivolumab is an anti-PD-1 immunotherapy that has been used in this setting. While immune related toxicity of these agents has been well described, the occurrence of immune specific neurotoxicity is thought to be rare. We present a case of severe encephalitis while on PD-1 immunotherapy for a recurrent ovarian clear cell cancer and we believe this to be the first such reported case associated with the use of PD-1 inhibitor monotherapy. In this case, a 64-year-old woman with persistent clear cell ovarian cancer on Nivolumab presented with a severe fever of unknown origin and delirium; initial imaging and diagnostic work-up suggested a neurological etiology, but with no clear source. We concluded that this was a severe case of immune related encephalitis, thought to be brought about by the anti-PD-1 immunotherapy which responded well to systemic corticosteroids and plasmapheresis and the patient able to make a full recovery. We present a summary of the case and its management as well as a review of the literature on the previously reported neurotoxicity's of PD-1 inhibitors.

  12. PD173074, a selective FGFR inhibitor, reverses MRP7 (ABCC10-mediated MDR

    Directory of Open Access Journals (Sweden)

    Nagaraju Anreddy

    2014-06-01

    Full Text Available Multidrug resistance protein 7 (MRP7, ABCC10 is a recently identified member of the ATP-binding cassette (ABC transporter family, which adequately confers resistance to a diverse group of antineoplastic agents, including taxanes, vinca alkaloids and nucleoside analogs among others. Clinical studies indicate an increased MRP7 expression in non-small cell lung carcinomas (NSCLC compared to a normal healthy lung tissue. Recent studies revealed increased paclitaxel sensitivity in the Mrp7−/− mouse model compared to their wild-type counterparts. This demonstrates that MRP7 is a key contributor in developing drug resistance. Recently our group reported that PD173074, a specific fibroblast growth factor receptor (FGFR inhibitor, could significantly reverse P-glycoprotein-mediated MDR. However, whether PD173074 can interact with and inhibit other MRP members is unknown. In the present study, we investigated the ability of PD173074 to reverse MRP7-mediated MDR. We found that PD173074, at non-toxic concentration, could significantly increase the cellular sensitivity to MRP7 substrates. Mechanistic studies indicated that PD173074 (1 μmol/L significantly increased the intracellular accumulation and in-turn decreased the efflux of paclitaxel by inhibiting the transport activity without altering expression levels of the MRP7 protein, thereby representing a promising therapeutic agent in the clinical treatment of chemoresistant cancer patients.

  13. Getting started with Microsoft Lync server 2013

    CERN Document Server

    Volpe, Fabrizio

    2013-01-01

    This book has a practical approach with a lot of step-by-step guides and explanations as to where and why we're doing the various operations.Getting Started with Microsoft Lync Server 2013 is a starting point for system administrators, IT pros, unified communication technicians, and decision makers in companies or in the consultancy business. For people who have never managed Lync (or a U.C. product), the book will guide you through the basic concepts and mistakes. If you are already managing a Lync deployment you will find important explanations and ideas put together in a single text. If you

  14. Soft start technique for diesel generator sets

    Energy Technology Data Exchange (ETDEWEB)

    Fredlund, Lars [Swedish State Power Board, Ringhals Nuclear Power Plant, S-430 22, Vaeroebacka (Sweden)

    1986-02-15

    A diesel motor in a nuclear power plant should be of a well-proven design. It is designed for long periods of trouble-free duty, but not for the frequent and rapid test starts called for by the technical specifications. In order to decrease the dynamic forces and thermal stresses, a soft-start scheme has been implemented. By limiting the fuel injection the diesel generator will reach full speed in appr. 30 seconds. The fuel limiter is a pneumatic cylinder which mechanically limits the travel of the terminal shaft of the governor. (author)

  15. Soft start technique for diesel generator sets

    International Nuclear Information System (INIS)

    Fredlund, Lars

    1986-01-01

    A diesel motor in a nuclear power plant should be of a well-proven design. It is designed for long periods of trouble-free duty, but not for the frequent and rapid test starts called for by the technical specifications. In order to decrease the dynamic forces and thermal stresses, a soft-start scheme has been implemented. By limiting the fuel injection the diesel generator will reach full speed in appr. 30 seconds. The fuel limiter is a pneumatic cylinder which mechanically limits the travel of the terminal shaft of the governor. (author)

  16. The Lean and Global Start-up

    DEFF Research Database (Denmark)

    Tanev, Stoyan; Rasmussen, Erik Stavnsager

    For several decades researchers have studied start-up companies with a focus on international markets, suppliers and networks from their inception and on companies that are establishing new, agile business models. This has resulted in two streams of research: The Born Global and International New...... Ventures research and research with a focus on the Lean Start-up company. It is our intention in this paper to give a short presentation of the two research streams and show how they can be merged into one with a focus on newly established technology oriented firms that are lean and global from...

  17. Entrepreneur How to Start an Online Business

    CERN Document Server

    Tobin, Lucy

    2012-01-01

    The secrets of the UK’s biggest online entrepreneurs revealed   Thinking of starting a business? Already have a business online and looking to take it to the next level? The wonderful world wide web has made creating a start-up that much easier. Thousands of people are out there reaping the rewards the web can bring. If you want to join them, you’ve come to the right place.  Profiling today’s foremost web entrepreneurs, Lucy Tobin - who meets successful business founders every week writing an enterprise column for The Evening Standard – takes us throug

  18. PD-1 Blockade Expands Intratumoral Memory T Cells

    DEFF Research Database (Denmark)

    Ribas, Antoni; Shin, Daniel Sanghoon; Zaretsky, Jesse

    2016-01-01

    by multicolor flow cytometry using two computational approaches to resolve the leukocyte phenotypes at the single-cell level. There was a statistically significant increase in the frequency of T cells in patients who responded to therapy. The frequency of intratumoral B cells and monocytic myeloid......-derived suppressor cells significantly increased in patients' biopsies taken on treatment. The percentage of cells with a regulatory T-cell phenotype, monocytes, and natural killer cells did not change while on