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Sample records for 1-year progression-free survival

  1. Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer

    MedlinePlus

    ... Prevention Lung Cancer Screening Research Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer ( ... starting treatment without their disease getting worse (progression-free survival), as assessed by radiologic review. Results Progression- ...

  2. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials

    PubMed Central

    Trippa, Lorenzo; Wen, Patrick Y.; Parmigiani, Giovanni; Berry, Donald A.; Alexander, Brian M.

    2015-01-01

    Background The use of auxiliary endpoints may provide efficiencies for clinical trial design, but such endpoints may not have intrinsic clinical relevance or clear linkage to more meaningful endpoints. The purpose of this study was to generate a novel endpoint that considers both overall survival (OS) and earlier events such as progression-free survival (PFS) and determine whether such an endpoint could increase efficiency in the design of glioblastoma clinical trials. Methods Recognizing that the association between PFS and OS varies depending on therapy and tumor type, we developed a statistical model to predict OS based on PFS as the trial progresses. We then evaluated the efficiency of our model using simulations of adaptively randomized trials incorporating PFS and OS distributions from prior published trials in neuro-oncology. Results When treatment effects on PFS and OS are concordant, our proposed approach results in efficiency gains compared with randomization based on OS alone while sacrificing minimal efficiency compared with using PFS as the primary endpoint. When treatment effects are limited to PFS, our approach provides randomization probabilities that are close to those based on OS alone. Conclusion Use of OS as the primary endpoint, combined with statistical modeling of the relationship between OS and PFS during the course of the trial, results in more robust and efficient trial designs than using either endpoint alone. PMID:25568226

  3. Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

    PubMed Central

    Beauchemin, Catherine; Cooper, Dan; Lapierre, Marie-Ève; Yelle, Louise; Lachaine, Jean

    2014-01-01

    Background Progression-free survival (PFS) and time to progression (TTP) are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS) remains a matter of uncertainty in metastatic breast cancer (mBC). This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach. Methods We conducted a systematic literature review according to the PICO method: ‘Population’ consisted of women with mBC; ‘Interventions’ and ‘Comparators’ were standard treatments for mBC or best supportive care; ‘Outcomes’ of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP. Results A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01). Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01). The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172) + 1.753 (95% CI 1.307–2.198) × ΔPFS (R2=0.86). Conclusion Results of this study indicate a significant association between PFS/TTP and OS in mBC, which may justify the use of PFS/TTP in the approval for commercialization and reimbursement of new anti-cancer drugs in this cancer setting. PMID:24971020

  4. Overview: Progression-Free Survival as an Endpoint in Clinical Trials with Solid Tumors

    PubMed Central

    Korn, Ronald L.; Crowley, John J.

    2013-01-01

    Progression-free survival (PFS) is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors, because of both practical and clinical considerations. Although in its simplest form PFS is the time from randomization to a pre-defined endpoint, there are many factors that can influence the exact moment of when disease progression is recorded. In this overview, we review the circumstances that can devalue the use of PFS as a primary endpoint, and attempt to provide a pathway for a future desired state when PFS will become not just a secondary alternative to overall survival but rather an endpoint of choice. PMID:23669420

  5. Autologous stem cell transplantation in first complete remission may not extend progression-free survival in patients with peripheral T cell lymphomas.

    PubMed

    Yam, Clinton; Landsburg, Daniel J; Nead, Kevin T; Lin, Xinyi; Mato, Anthony R; Svoboda, Jakub; Loren, Alison W; Frey, Noelle V; Stadtmauer, Edward A; Porter, David L; Schuster, Stephen J; Nasta, Sunita D

    2016-07-01

    Patients with peripheral T cell lymphomas (PTCL) generally have a poor prognosis when treated with conventional chemotherapy. Consolidation with autologous stem cell transplantation (ASCT) has been reported to improve progression-free survival. However, these studies have not compared consolidative ASCT with active observation in patients with PTCL achieving first complete remission (CR1) following induction chemotherapy. We conducted a retrospective analysis of PTCL patients treated at the University of Pennsylvania between 1/1/2007 and 12/31/2014. Patients with cutaneous T cell lymphoma, concurrent B cell lymphomas, and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-positive ALCL) were excluded from the study. We compared progression-free survival for patients who underwent ASCT in CR1 following CHOP-like induction regimens and patients who underwent active observation during CR1. 48 patients met all inclusion and exclusion criteria and underwent either active observation (28 patients) or consolidative ASCT (20 patients) in CR1. The 1-year cumulative incidence of relapse in the observation and ASCT groups was 50% (95% confidence interval [CI]: 30-67%) and 46% (95% CI: 23-67%), respectively (P = 0.55). Median progression-free survival in the observation and ASCT groups was 15.8 and 12.8 months, respectively (log rank, P = 0.79). Estimated 3-year progression-free survival in the observation and ASCT groups was 37 and 41%, respectively. In conclusion, for PTCL patients achieving CR1 following CHOP-like induction chemotherapy, ASCT does not appear to improve progression-free survival compared to active observation. This finding should be confirmed in a larger, prospective study. Am. J. Hematol. 91:672-676, 2016. © 2016 Wiley Periodicals, Inc. PMID:27012928

  6. Joint modeling of progression-free survival and death in advanced cancer clinical trials.

    PubMed

    Dejardin, David; Lesaffre, Emmanuel; Verbeke, Geert

    2010-07-20

    Progression-related endpoints (such as time to progression or progression-free survival) and time to death are common endpoints in cancer clinical trials. It is of interest to study the link between progression-related endpoints and time to death (e.g. to evaluate the degree of surrogacy). However, current methods ignore some aspects of the definitions of progression-related endpoints. We review those definitions and investigate their impact on modeling the joint distribution. Further, we propose a multi-state model in which the association between the endpoints is modeled through a frailty term. We also argue that interval-censoring needs to be taken into account to more closely match the latent disease evolution. The joint distribution and an expression for Kendall's tau are derived. The model is applied to data from a clinical trial in advanced metastatic ovarian cancer. PMID:20572123

  7. The role of censoring on progression free survival: oncologist discretion advised.

    PubMed

    Prasad, Vinay; Bilal, Usama

    2015-11-01

    Censoring is increasingly appreciated as a potential bias affecting estimates of progression free survival (PFS) in randomised trials. In this commentary, we explore the central assumption of censoring. Censored patients are considered no more or less likely to undergo the event of interest than those who remain in the analysis. Instead however, if one makes alternate assumptions, that censored patients are different than those who remain on the trial, estimates of PFS change. Using the example of the recent BOLERO-2 trial of exemestane and everolimus, we show that by altering the assumptions for censoring, the major conclusions of clinical trials may change. As such, the number of censored patients at each time interval should be routinely reported in randomised trials to better understand the implications of censoring. PMID:26259493

  8. Progression free survival and functional outcome after surgical resection of intramedullary ependymomas.

    PubMed

    Abdullah, Kalil G; Lubelski, Daniel; Miller, Jacob; Steinmetz, Michael P; Shin, John H; Krishnaney, Ajit; Mroz, Thomas E; Benzel, Edward C

    2015-12-01

    We present a 15 year institutional analysis of the factors affecting progression free survival (PFS) and overall survival (OS) in patients undergoing attempted resection of adult intramedullary spinal cord ependymomas. Intramedullary spinal cord tumors are rare but important clinical entities, and ependymomas are the most commonly encountered intramedullary tumor. In total, 53 adult patients over the span of 15 years were analyzed for OS, PFS, and the effects of plane of dissection (POD) and gross total resection (GTR) on functional and long term outcomes. The mean age was 45 years and median follow-up was 54 months. The follow-up neurological outcome and modified McCormick scale were used to determine the functional outcome. Kaplan-Meier curves were used to calculate progression and survival. The overall ability to achieve GTR was significantly correlated to identification of an intraoperative POD (p<0.001). There was a trend towards increased PFS with the ability to achieve a GTR. There was no significant difference in the pre- and postoperative functional outcome scores. The ability to achieve a GTR is strongly correlated to the identification of a POD in ependymomas. There is a trend towards an increased probability of PFS in intramedullary spinal cord tumors when GTR is achieved. The resection of these tumors is likely to halt, but not reverse, neurological deterioration. PMID:26234635

  9. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    PubMed

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma. PMID:27017948

  10. Estimation of Progression-Free Survival for All Treated Patients in the Randomized Discontinuation Trial Design

    PubMed Central

    Karrison, Theodore G.; Ratain, Mark J.; Stadler, Walter M.; Rosner, Gary L.

    2013-01-01

    The randomized discontinuation trial (RDT) design is an enrichment-type design that has been used in a variety of diseases to evaluate the efficacy of new treatments. The RDT design seeks to select a more homogeneous group of patients, consisting of those who are more likely to show a treatment benefit if one exists. In oncology, the RDT design has been applied to evaluate the effects of cytostatic agents, that is, drugs that act primarily by slowing tumor growth rather than shrinking tumors. In the RDT design, all patients receive treatment during an initial, open-label run-in period of duration T. Patients with objective response (substantial tumor shrinkage) remain on therapy while those with early progressive disease are removed from the trial. Patients with stable disease (SD) are then randomized to either continue active treatment or switched to placebo. The main analysis compares outcomes, for example, progression-free survival (PFS), between the two randomized arms. As a secondary objective, investigators may seek to estimate PFS for all treated patients, measured from the time of entry into the study, by combining information from the run-in and post run-in periods. For t ≤ T, PFS is estimated by the observed proportion of patients who are progression-free among all patients enrolled. For t > T, the estimate can be expressed as Ŝ(t) = p̂OR × ŜOR(t − T) + p̂SD × ŜSD(t − T), where p̂OR is the estimated probability of response during the run-in period, p̂SD is the estimated probability of SD, and ŜOR(t − T) and ŜSD(t − T) are the Kaplan–Meier estimates of subsequent PFS in the responders and patients with SD randomized to continue treatment, respectively. In this article, we derive the variance of Ŝ(t), enabling the construction of confidence intervals for both S(t) and the median survival time. Simulation results indicate that the method provides accurate coverage rates. An interesting aspect of the design is that outcomes during the

  11. Progression-Free Survival: An Important Prognostic Marker for Long-Term Survival of Small Cell Lung Cancer

    PubMed Central

    Park, Myoung-Rin; Park, Yeon-Hee; Choi, Jae-Woo; Park, Dong-Il; Chung, Chae-Uk; Moon, Jae-Young; Park, Hee-Sun; Jung, Sung-Soo; Kim, Ju-Ock; Kim, Sun-Young

    2014-01-01

    Background Small cell lung cancer (SCLC) is an extremely aggressive tumor with a poor clinical course. Although many efforts have been made to improve patients' survival rates, patients who survive longer than 2 years after chemotherapy are still very rare. We examined the baseline characteristics of patients with long-term survival rates in order to identify the prognostic factors for overall survivals. Methods A total of 242 patients with cytologically or histologically diagnosed SCLC were enrolled into this study. The patients were categorized into long- and short-term survival groups by using a survival cut-off of 2 years after diagnosis. Cox's analyses were performed to identify the independent factors. Results The mean patient age was 65.66 years, and 85.5% were males; among the patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06; p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression-free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p<0.001) were independent prognostic markers for poor survival rates. Conclusion In addition to other well-known prognostic factors, this study discovered relationships between the long-term survival rates and serum CRP levels, TNM staging, and PFS. In situations with unfavorable conditions, the PFS would be particularly helpful for managing SCLC patients. PMID:24920948

  12. The imaging viewpoint: how imaging affects determination of progression-free survival.

    PubMed

    Sullivan, Daniel Carl; Schwartz, Lawrence H; Zhao, Binsheng

    2013-05-15

    Tumor measurements on computed tomgoraphic or MRI scans and/or the appearance of new lesions on any of a variety of imaging studies including positron emission tomographic scans are key determinants for assessing progression-free survival as an endpoint in many clinical trials of therapies for solid tumors. Test-retest tumor measurement reproducibility may vary considerably across serial scans on the same patient unless rigorous attention is paid to standardization of image acquisition parameters and unless measurements are made by trained, experienced observers using validated objective methods. Target lesion selection also must be done with care to choose lesions that are or will be reproducibly measurable. Likewise, new lesions will be missed or misinterpreted on follow-up imaging studies unless those imaging studies are obtained using techniques suitable for detecting early, small lesions. Reader variability is clearly a major component of the problem. The increasing availability of semiautomatic image processing algorithms will help ameliorate that issue. In addition, an array of internationally accepted guidelines, standards, and accreditation programs now exist to help address these problems. PMID:23669422

  13. Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients.

    PubMed

    Tada, Kohei; Kitano, Shigehisa; Shoji, Hirokazu; Nishimura, Takashi; Shimada, Yasuhiro; Nagashima, Kengo; Aoki, Kazunori; Hiraoka, Nobuyoshi; Honma, Yoshitaka; Iwasa, Satoru; Okita, Natsuko; Takashima, Atsuo; Kato, Ken; Yamada, Yasuhide; Katayama, Naoyuki; Boku, Narikazu; Heike, Yuji; Hamaguchi, Tetsuya

    2016-07-01

    It remains unclear whether the immunologic status of cells in peripheral blood can be used as a prognostic indicator of response to treatment for patients with unresectable metastatic colorectal cancer (MCRC). We therefore investigated the relationship between the pretreatment immunologic status of 40 patients with MCRC who planned to receive the first-line chemotherapy and their progression-free survival. Twenty-five immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSC) and effector memory T cells (TEM), were measured by multicolor-flow cytometry. We divided patients into high and low (above and below the median, respectively) groups based on the median value for each immune cell subset and compared progression-free survival of the two groups. Patients with high M-MDSC, low CD4(+) TEM, or low CD8(+) TEM quantities had significantly shorter progression-free survival (P = 0.004, 0.005, and 0.002, respectively). Patients were classified into two prognostic groups based on numbers of adverse factors; having two or three adverse factors (n = 21, 52.5%) was correlated with significantly shorter progression-free survival compared with none or one (n = 19, 47.5%; P < 0.001). The presence of two or three adverse factors was an independent poor prognostic factor for progression-free survival (HR, 9.2; 95% confidence interval, 2.5-34.2; P < 0.001). These results provide evidence that pretreatment peripheral immune status can inform the outcome of patients with MCRC treated with first-line chemotherapy. Cancer Immunol Res; 4(7); 592-9. ©2016 AACR. PMID:27197061

  14. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma

    PubMed Central

    Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A.; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A. Keith; Obreja, Mihaela; Moreau, Philippe

    2016-01-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. PMID:27439911

  15. Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma.

    PubMed

    Kucharz, Jakub; Giza, Agnieszka; Dumnicka, Paulina; Kuzniewski, Marek; Kusnierz-Cabala, Beata; Bryniarski, Pawel; Herman, Roma; Zygulska, Aneta Lidia; Krzemieniecki, Krzysztof

    2016-10-01

    Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in 'low' and 'intermediate' Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81-0.99) and 0.76 (0.65-0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib's inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential. PMID:27573381

  16. Carboplatin–paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer

    PubMed Central

    Lee, C K; Gurney, H; Brown, C; Sorio, R; Donadello, N; Tulunay, G; Meier, W; Bacon, M; Maenpaa, J; Petru, E; Reed, N; Gebski, V; Pujade-Lauraine, E; Lord, S; Simes, R J; Friedlander, M

    2011-01-01

    Background: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin–paclitaxel (CP) or carboplatin–liposomal doxorubicin (CPLD). Methods: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 109 per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS. Results: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin–liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008). Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin–liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15). Conclusion: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity. PMID:21750553

  17. Allotransplantation for patients age ≥40 years with non-Hodgkin lymphoma: encouraging progression-free survival.

    PubMed

    McClune, Brian L; Ahn, Kwang Woo; Wang, Hai-Lin; Antin, Joseph H; Artz, Andrew S; Cahn, Jean-Yves; Deol, Abhinav; Freytes, César O; Hamadani, Mehdi; Holmberg, Leona A; Jagasia, Madan H; Jakubowski, Ann A; Kharfan-Dabaja, Mohamed A; Lazarus, Hillard M; Miller, Alan M; Olsson, Richard; Pedersen, Tanya L; Pidala, Joseph; Pulsipher, Michael A; Rowe, Jacob M; Saber, Wael; van Besien, Koen W; Waller, Edmund K; Aljurf, Mahmoud D; Akpek, Görgun; Bacher, Ulrike; Chao, Nelson J; Chen, Yi-Bin; Cooper, Brenda W; Dehn, Jason; de Lima, Marcos J; Hsu, Jack W; Lewis, Ian D; Marks, David I; McGuirk, Joseph; Cairo, Mitchell S; Schouten, Harry C; Szer, Jeffrey; Ramanathan, Muthalagu; Savani, Bipin N; Seftel, Matthew; Socie, Gérard; Vij, Ravi; Warlick, Erica D; Weisdorf, Daniel J

    2014-07-01

    Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood and Marrow Transplant Research data on 1248 patients age ≥40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL. Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age ≥65; P = .0008). Fewer patients aged ≥65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% [95% confidence interval (CI), 19% to 26%] for age 40 to 54, 27% [95% CI, 23% to 31%] for age 55 to 64, and 34% [95% CI, 24% to 44%] for age ≥65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% [95% CI, 50% to 58%] for age 40 to 54; 40% [95% CI, 36% to 44%] for age 55 to 64, and 39% [95% CI, 28% to 50%] for age ≥65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age ≥55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age ≥55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL. PMID:24641829

  18. Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy.

    PubMed

    Pfütze, Katrin; Benner, Axel; Hoffmeister, Michael; Jansen, Lina; Yang, Rongxi; Bläker, Hendrik; Herpel, Esther; Ulrich, Alexis; Ulrich, Cornelia M; Chang-Claude, Jenny; Brenner, Hermann; Burwinkel, Barbara

    2015-12-01

    DNA methylation variations in gene promoter regions are well documented tumor-specific alterations in human malignancies including colon cancer, which may influence tumor behavior and clinical outcome. As a subset of colon cancer patients does not benefit from adjuvant chemotherapy, predictive biomarkers are desirable. Here, we describe that DNA methylation levels at CpG loci of hyaluronoglucosaminidase 2 (HYLA2) could be used to identify stage II and III colon cancer patients who are most likely to benefit from 5-flourouracil (5-FU) chemotherapy with respect to overall survival and progression-free survival. PMID:26453961

  19. Relationship between progression-free survival and overall survival in chronic lymphocytic leukemia: a literature-based analysis

    PubMed Central

    Beauchemin, C.; Johnston, J.B.; Lapierre, M.È.; Aissa, F.; Lachaine, J.

    2015-01-01

    Background The endpoints of progression-free survival (pfs) and time-to-progression (ttp) are frequently used to evaluate the clinical benefit of anticancer drugs. However, the surrogacy of those endpoints for overall survival (os) is not validated in all cancer settings. In the present study, we used a trial-based approach to assess the relationship between median pfs or ttp and median os in chronic lymphocytic leukemia (cll). Methods The pico (population, interventions, comparators, outcomes) method was used to conduct a systematic review of the literature. The population consisted of patients with cll; the interventions and comparators were standard therapies for cll; and the outcomes were median pfs, ttp, and os. Two independent reviewers screened titles, abstracts, and full papers for eligibility and then extracted data from selected studies. Correlation coefficients were calculated to assess the relationship between median pfs or ttp and median os. Subgroup correlation analyses were also conducted according to the characteristics of the selected studies (such as line of treatment and type of treatment under investigation). Results Of the 1263 potentially relevant articles identified during the literature search, twenty-three were included. On average, median pfs or ttp was 16.0 months (standard deviation: 12.4 months) and median os was 43.5 months (standard deviation: 31.2 months). Results of the correlation analysis indicated that median pfs or ttp is highly correlated with median os (Spearman correlation coefficient: 0.813; p ≤ 0.001). A significant correlation between median pfs or ttp and median os was observed in second- and subsequent-line therapies, but not in the first-line setting. Conclusions Our study demonstrates a strong correlation between median pfs or ttp and median os in previously treated cll, which reinforce the hypothesis that pfs and ttp could be adequate surrogate endpoints for os in this cancer setting. PMID:26089725

  20. Progression-Free Survival Remains Poor Over Sequential Lines of Systemic Therapy in Patients with BRAF-mutated Colorectal Cancer

    PubMed Central

    Morris, Van K.; Overman, Michael J.; Jiang, Zhi-Qin; Garrett, Chris; Agarwal, Shweta; Eng, Cathy; Kee, Bryan; Fogelman, David; Dasari, Arvind; Wolff, Robert; Maru, Dipen; Kopetz, Scott

    2014-01-01

    Background BRAF mutations occur in 5–10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described. Methods We searched the MD Anderson Cancer Center databases for patients with colorectal cancer patients and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, progression-free survival (PFS), overall survival (OS), and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method. Results Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first three lines of chemotherapy, median progression-free survivals were 6.3 months (n=69 patients, 95% confidence interval (CI) of 4.9–7.7 months), 2.5 months (n=58, 95% CI of 1.8–3.0 months), and 2.6 months (n=31, 95% CI of 1.0–4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively, p-value = 0.99). Conclusions Progression-free survival is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present (with testing preferentially performed in patients suitable for clinical trials in refractory disease), these data provide historic controls suitable for future study design and support the idea that novel therapeutic options are essential in this population. PMID:25069797

  1. Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

    PubMed Central

    2012-01-01

    Background Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC) patients with an activating mutation in the epidermal growth factor receptor (EGFR). Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+). From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis); pemetrexed/cisplatin (Pem/Cis); paclitaxel/carboplatin (Pac/Carb)) in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. Methods Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS). Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS) to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. Results The Quality Adjusted progression free survival (PFS) (mean, (95% credibility interval)) was 5.2 months (4.5; 5.8) for Gem/Cis, 5.3 months (4.6; 6.1) for Pem/Cis; 4.9 months (4.4; 5.5) for Pac/Carb and 8.3 (7.0; 9.9) for

  2. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas.

    PubMed

    Lamborn, Kathleen R; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; DeAngelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Fink, Karen L; Junck, Larry; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Hibberts, Janelle; Peterson, Pamela M; Prados, Michael D

    2008-04-01

    The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials. PMID:18356283

  3. Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas

    PubMed Central

    Lamborn, Kathleen R.; Alfred Yung, W. K.; Chang, Susan M.; Wen, Patrick Y.; Cloughesy, Timothy F.; DeAngelis, Lisa M.; Robins, H. Ian; Lieberman, Frank S.; Fine, Howard A.; Fink, Karen L.; Junck, Larry; Abrey, Lauren; Gilbert, Mark R.; Mehta, Minesh; Kuhn, John G.; Aldape, Kenneth D.; Hibberts, Janelle; Peterson, Pamela M.; Prados, Michael D.

    2008-01-01

    The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials. PMID:18356283

  4. [Bevacizumab as first-line therapy in metastatic renal cell carcinoma : Progression-free survival for 3 years].

    PubMed

    Pichler, R; Horninger, W; Aigner, F; Heidegger, I

    2016-03-01

    We report the case of a 72-year-old woman who was diagnosed in 2006 with renal cell cancer (RCC) and had undergone consecutive tumor nephrectomy (clear-cell RCC, Fuhrmann grade II, stage pT3a, R0). Over the years, the patient underwent several surgical and radiological interventions due to various metastatic lesions. This case report describes the 3-year progression-free survival in a patient who underwent first-line therapy with the monoclonal antibody bevacizumab. Except for hypertension, the patient does not suffer currently from any other side effects of bevacizumab therapy. PMID:26471795

  5. Effects of Concurrent Topotecan and Radiation on 6-Month Progression-Free Survival in the Primary Treatment of Glioblastoma Multiforme

    SciTech Connect

    Grabenbauer, Gerhard G. Gerber, Klaus-Dieter; Ganslandt, Oliver; Richter, Andrea M.S.; Klautke, Gunther; Birkmann, Josef; Meyer, Martin

    2009-09-01

    Purpose: To report a prospective, randomized, Phase II trial of radiotherapy with and without topotecan for the treatment of glioblastoma. Patients and Methods: Inclusion criteria were histology of glioblastoma, age <60 years, and Eastern Cooperative Oncology Group status 0-2. Patients were stratified according to recursive partitioning analysis class, center, and enzyme-inducing antiepileptic medication. Magnetic resonance imaging scans, neurologic examinations, and quality of life assessments were done every 3 months. The primary endpoint was the progression-free survival rate at 6 months (6-m-PFS). This trial was designed as an exploratory, randomized, Phase II trial with an accrual of 140 patients to detect a difference of 15-20% in 6-m-PFS. An interim analysis was scheduled after 60 patients. Median follow-up was 14 months (range, 1-50 months). Results: The 6-m-PFS was 56% and 40% for patients with and without topotecan, respectively. This benefit disappeared within 2 months. Mean (range) progression-free survival time was 8 (5-10.9) months and 6.7 (4-9.5) months for patients with and without topotecan, respectively. The corresponding 2-year-overall survival rates were 28% vs. 22% (nonsignificant difference), and mean (range) survival time was 20.7 (13.9-27.5) months vs. 18.9 (13.5-24.4) months (nonsignificant difference). Conclusions: A slight but measurable increase of 16% was detected in 6-m-PFS for patients receiving topotecan with radiation as compared with patients having radiotherapy alone. These data might support further investigations into topotecan for the treatment of glioblastoma.

  6. Long-Term Progression-Free Survival in a Patient with Locally Advanced, Unresectable Pancreatic Adenocarcinoma

    PubMed Central

    Kahn, Leonel A; Matin, Mahan; Bold, Richard J; Tanaka, Michael I; Monjazeb, Arta M

    2015-01-01

    Pancreatic adenocarcinoma is amongst the most lethal malignancies with dismal five-year survival rates. Surgical excision is the mainstay of therapy and unresectable disease is considered incurable. Herein, we describe a patient with unresectable, advanced stage pancreatic adenocarcinoma with a remarkable clinical course following definitive chemoradiotherapy. PMID:26824007

  7. Low expression of ARHI is associated with shorter progression-free survival in pancreatic endocrine tumors.

    PubMed

    Dalai, Irene; Missiaglia, Edoardo; Barbi, Stefano; Butturini, Giovanni; Doglioni, Claudio; Falconi, Massimo; Scarpa, Aldo

    2007-03-01

    Little is known about the molecular anomalies involved in the development and progression of malignancy of pancreatic endocrine tumors (PETs). A recently identified member of the Ras family, Ras homologue member I (ARHI), has been shown to be involved in breast, ovary, and thyroid carcinogenesis. Unlike other members, it acts as a tumor suppressor gene that inhibits cell growth. Here we analyzed the mRNA expression of ARHI in 52 primary PETs and 16 normal pancreata using quantitative reverse transcription-polymerase chain reaction. ARHI expression showed a statistically significant difference between either normal pancreas or well-differentiated endocrine tumors (WDET) and poorly differentiated endocrine carcinomas (PDECs) (P < .001 and P < .001, respectively). Moreover, ARHI expression among WDEC samples was more heterogeneous than in WDET, with several tumors showing level of expression analogous to that observed in PDECs. A significant correlation between lower ARHI expression and shorter survival (P = .020) was identified, and a low ARHI expression was associated to a shorter time to progression (P < .001), even considering the proliferation index Ki67 in the multivariate analysis. ARHI is involved in PET progression. Its mRNA expression seemed to be a prognostic factor for disease outcome and, in association with the proliferative index Ki67, a predictor for a rapid tumor relapse. PMID:17401457

  8. Detection of Critical Genes Associated with Overall Survival (OS) and Progression-Free Survival (PFS) in Reconstructed Canine B-Cell Lymphoma Gene Regulatory Network (GRN).

    PubMed

    Zamani-Ahmadmahmudi, Mohamad; Najafi, Ali; Nassiri, Seyed Mahdi

    2016-01-01

    Canine B-cell lymphoma GRN was reconstructed from gene expression data in the STRING and MiMI databases. Critical genes of networks were identified and correlations of critical genes with overall survival (OS) and progression-free survival (PFS) were evaluated. Significant changes were detected in the expressions of GLUL, CD44, CD79A, ARF3, FOS, BLOC1S1, FYN, GZMB, GALNT3, IFI44, CD3G, GNG2, ESRP1, and CCND1 in the STRING network and of PECAM1, GLUL, CD44, GDI1, E2F4, TLE1, CD79A, UCP2, CCND1, FYN, RHOQ, BIN1, and A2M in the MiMI network. Final survival analysis highlighted CCND1 and FOS as genes with significant correlations with OS and PFS. PMID:26818715

  9. Allotransplantation for patients age 40 years and greater with non-Hodgkin Lymphoma (NHL): encouraging progression-free survival

    PubMed Central

    McClune, Brian L.; Ahn, Kwang Woo; Wang, Hai-Lin; Antin, Joseph H.; Artz, Andrew S.; Cahn, Jean-Yves; Deol, Abhinav; Freytes, César O.; Hamadani, Mehdi; Holmberg, Leona A.; Jagasia, Madan H.; Jakubowski, Ann A.; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Miller, Alan M.; Olsson, Richard; Pedersen, Tanya L.; Pidala, Joseph; Pulsipher, Michael A.; Rowe, Jacob M.; Saber, Wael; van Besien, Koen W.; Waller, Edmund K.; Aljurf, Mahmoud D.; Akpek, Görgun; Bacher, Ulrike; Chao, Nelson J.; Chen, Yi-Bin; Cooper, Brenda W.; Dehn, Jason; de Lima, Marcos J.; Hsu, Jack W.; Lewis, Ian D.; Marks, David I.; McGuirk, Joseph; Cairo, Mitchell S.; Schouten, Harry C.; Szer, Jeffrey; Ramanathan, Muthalagu; Savani, Bipin N.; Seftel, Matthew; Socie, Gérard; Vij, Ravi; Warlick, Erica D.; Weisdorf, Daniel J.

    2014-01-01

    Non-Hodgkin lymphomas (NHL) disproportionately affect older patients who uncommonly receive allogeneic hematopoietic cell transplantation (HCT). We analyzed CIBMTR data on 1248 patients ≥40 years receiving reduced-intensity conditioning (RIC) or non-myeloablative (NMA) HCT for aggressive (n=668) and indolent (n=580) NHL. Aggressive lymphoma was more frequent in the oldest cohort [(age 40–54) 49% vs. (55–64) 57% vs. (≥65) 67% p=0.0008]; fewer patients ≥65 had prior autografting [26% vs. 24% vs. 9%; p=0.002)]. Rates of relapse, acute and chronic GVHD and non-relapse mortality (NRM) at one year were similar [22%, 95% confidence interval (CI) 19–26%; 27%, 95% CI 23–31%; 34%, 95% CI 24–44%]. Progression-free (PFS) and overall (OS) survival at 3 years was slightly lower in older cohorts [OS:54%, 95% CI 50–58%; 40%, 95% CI 36–44%; 39%, 95% CI 28–50%; p<0.0001]. Multivariate analysis revealed no significant effect of age on acute or chronic GVHD or relapse. Age ≥55 years, Karnofsky performance status <80, and HLA-mismatch adversely impacted NRM, PFS, and OS. Disease status at HCT, but not histologic subtype, worsened NRM, relapse, PFS and OS. Even for patients ≥55 years, OS still approached 40% at 3 years suggesting HCT effects long-term remissions and remains underutilized in qualified older patients with NHL. PMID:24641829

  10. Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer

    PubMed Central

    French, Juliet D.; Johnatty, Sharon E.; Lu, Yi; Beesley, Jonathan; Gao, Bo; Kalimutho, Murugan; Henderson, Michelle J.; Russell, Amanda J.; Kar, Siddhartha; Chen, Xiaoqing; Hillman, Kristine M.; Kaufmann, Susanne; Sivakumaran, Haran; O'Reilly, Martin; Wang, Chen; Korbie, Darren J.; Lambrechts, Diether; Despierre, Evelyn; Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Vergote, Ignace; Karlan, Beth; Lester, Jenny; Orsulic, Sandra; Walsh, Christine; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Matsuo, Keitaro; Hosono, Satoyo; Pisterer, Jacobus; Hillemanns, Peter; Nakanishi, Toru; Yatabe, Yasushi; Goodman, Marc T.; Lurie, Galina; Matsuno, Rayna K.; Thompson, Pamela J.; Pejovic, Tanja; Bean, Yukie; Heitz, Florian; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan; Hogdall, Claus; Lundvall, Lene; Engelholm, Svend Aage; Brown, Bob; Flanagan, James M.; Metcalf, Michelle D.; Siddiqui, Nadeem; Sellers, Thomas; Fridley, Brooke; Cunningham, Julie; Schildkraut, Joellen M.; Iversen, Ed; Weber, Rachel Palmieri; Brennan, Donal; Berchuck, Andrew; Pharoah, Paul; Harnett, Paul; Norris, Murray D.; Haber, Michelle; Goode, Ellen L.; Lee, Jason S.; Khanna, Kum Kum; Meyer, Kerstin B.; Chenevix-Trench, Georgia; deFazio, Anna; Edwards, Stacey L.; MacGregor, Stuart

    2016-01-01

    Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7×10−5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression. PMID:26840454

  11. Anemia before and during concurrent chemoradiotherapy in patients with cervical carcinoma: Effect on progression-free survival.

    PubMed

    Obermair, A; Cheuk, R; Horwood, K; Neudorfer, M; Janda, M; Giannis, G; Nicklin, J L; Perrin, L C; Crandon, A J

    2003-01-01

    To determine the impact of anemia before and during chemoradiation in patients with cervical cancer, we collected data on hemoglobin (Hb) levels before and during treatment from 60 unselected patients with cervical carcinoma. All patients had FIGO stage IB to IVA disease and were treated with concurrent chemoradiation for the aim of cure. Patients with an Hb value below or equal to the lower 25th quartile were considered anemic. Progression-free survival (PFS) was evaluated by univariate and multivariate analyses. After a median follow-up of 26.3 months, 20 patients developed disease progression. The lowest Hb during chemoradiation (nadir Hb), the stage of disease, and parametrial involvement were correlated significantly with PFS. On multivariate analysis, the nadir Hb (relative risk [RR] 0.29) and tumor stage (RR 3.4) remained the only prognostically relevant factors predicting PFS. At 60 months the PFS was 39.1% for anemic patients and 48.0% for nonanemic patients (P < 0.0002). In patients undergoing chemoradiation for cervical carcinoma, a low nadir Hb is highly predictive of shortened PFS, whereas the Hb before treatment is prognostically not significant. PMID:14675347

  12. Prognostic nomogram to predict progression-free survival in patients with platinum-sensitive recurrent ovarian cancer

    PubMed Central

    Lee, C K; Simes, R J; Brown, C; Lord, S; Wagner, U; Plante, M; Vergote, I; Pisano, C; Parma, G; Burges, A; Bourgeois, H; Högberg, T; Bentley, J; Angleitner-Boubenizek, L; Ferrero, A; Richter, B; Hirte, H; Gebski, V; Pfisterer, J; Pujade-Lauraine, E; Friedlander, M

    2011-01-01

    Background: Patients with platinum-sensitive recurrent ovarian cancer are a heterogeneous group, and it is not possible to accurately predict the progression-free survival (PFS) in these patients. We developed and validated a nomogram to help improve prediction of PFS in patients treated with platinum-based chemotherapy. Methods: The nomogram was developed in a training cohort (n=955) from the CALYPSO trial and validated in the AGO-OVAR 2.5 Study (n=340). The proportional-hazards model (nomogram) was based on pre-treatment characteristics. Results: The nomogram had a concordance index (C-index) of 0.645. Significant predictors were tumour size platinum-chemotherapy-free interval, CA-125, number of organ metastatic sites and white blood count. When the nomogram was applied without CA-125 (CA-125 was not available in validation cohort), the C-indices were 0.624 (training) and 0.594 (validation). When classification was based only on the platinum-chemotherapy-free interval, the indices were 0.571 (training) and 0.560 (validation). The calibration plot in the validation cohort based on four predictors (without CA-125) suggested good agreement between actual and nomogram-predicted 12-month PFS probabilities. Conclusion: This nomogram, using five pre-treatment characteristics, improves prediction of PFS in patients with platinum-sensitive ovarian cancer having platinum-based chemotherapy. It will be useful for the design and stratification of patients in clinical trials and also for counselling patients. PMID:21915127

  13. Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer.

    PubMed

    French, Juliet D; Johnatty, Sharon E; Lu, Yi; Beesley, Jonathan; Gao, Bo; Kalimutho, Murugan; Henderson, Michelle J; Russell, Amanda J; Kar, Siddhartha; Chen, Xiaoqing; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; O'Reilly, Martin; Wang, Chen; Korbie, Darren J; Lambrechts, Diether; Despierre, Evelyn; Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Vergote, Ignace; Karlan, Beth; Lester, Jenny; Orsulic, Sandra; Walsh, Christine; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Matsuo, Keitaro; Hosono, Satoyo; Pisterer, Jacobus; Hillemanns, Peter; Nakanishi, Toru; Yatabe, Yasushi; Goodman, Marc T; Lurie, Galina; Matsuno, Rayna K; Thompson, Pamela J; Pejovic, Tanja; Bean, Yukie; Heitz, Florian; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Estrid; Kjaer, Susanne K; Jensen, Allan; Hogdall, Claus; Lundvall, Lene; Engelholm, Svend Aage; Brown, Bob; Flanagan, James M; Metcalf, Michelle D; Siddiqui, Nadeem; Sellers, Thomas; Fridley, Brooke; Cunningham, Julie; Schildkraut, Joellen M; Iversen, Ed; Weber, Rachel Palmieri; Brennan, Donal; Berchuck, Andrew; Pharoah, Paul; Harnett, Paul; Norris, Murray D; Haber, Michelle; Goode, Ellen L; Lee, Jason S; Khanna, Kum Kum; Meyer, Kerstin B; Chenevix-Trench, Georgia; deFazio, Anna; Edwards, Stacey L; MacGregor, Stuart; On Behalf Of The Ovarian Cancer Association Consortium

    2016-02-01

    Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7x10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression. PMID:26840454

  14. Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation.

    PubMed

    Bachanova, Veronika; Weisdorf, Daniel J; Wang, Tao; Marsh, Steven G E; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R; Ladner, Martha; Guethlein, Lisbeth A; Parham, Peter; Miller, Jeffrey S; Cooley, Sarah A

    2016-09-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. PMID:27220262

  15. MGMT promoter methylation is associated with temozolomide response and prolonged progression-free survival in disseminated cutaneous melanoma.

    PubMed

    Tuominen, Rainer; Jewell, Rosalyn; van den Oord, Joost J; Wolter, Pascal; Stierner, Ulrika; Lindholm, Christer; Hertzman Johansson, Carolina; Lindén, Diana; Johansson, Hemming; Frostvik Stolt, Marianne; Walker, Christy; Snowden, Helen; Newton-Bishop, Julia; Hansson, Johan; Egyházi Brage, Suzanne

    2015-06-15

    To investigate the predictive and prognostic value of O(6) -methylguanine DNA methyltransferase (MGMT) inactivation by analyses of promoter methylation in pretreatment tumor biopsies from patients with cutaneous melanoma treated with dacarbazine (DTIC) or temozolomide (TMZ) were performed. The patient cohorts consisted of Belgian and Swedish disseminated melanoma patients. Patients were subdivided into those receiving single-agent treatment with DTIC/TMZ (cohort S, n = 74) and those treated with combination chemotherapy including DTIC/TMZ (cohort C, n = 79). Median follow-up was 248 and 336 days for cohort S and cohort C, respectively. MGMT promoter methylation was assessed by three methods. The methylation-related transcriptional silencing of MGMT mRNA expression was assessed by real-time RT-PCR. Response to chemotherapy and progression-free survival (PFS) and overall survival were correlated to MGMT promoter methylation status. MGMT promoter methylation was detected in tumor biopsies from 21.5 % of the patients. MGMT mRNA was found to be significantly lower in tumors positive for MGMT promoter methylation compared to tumors without methylation in both treatment cohorts (p < 0.005). DTIC/TMZ therapy response rate was found to be significantly associated with MGMT promoter methylation in cohort S (p = 0.0005), but did not reach significance in cohort C (p = 0.16). Significantly longer PFS was observed among patients with MGMT promoter-methylated tumors (p = 0.002). Multivariate Cox regression analysis identified presence of MGMT promoter methylation as an independent variable associated with longer PFS. Together, this implies that MGMT promoter methylation is associated with response to single-agent DTIC/TMZ and longer PFS in disseminated cutaneous melanoma. PMID:25400033

  16. Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts

    PubMed Central

    Ghesquières, Hervé; Maurer, Matthew J.; Casasnovas, Olivier; Ansell, Stephen M.; Larrabee, Beth R.; Lech-Maranda, Eva; Novak, Anne J.; Borrel, Anne-Laure; Slager, Susan L.; Brice, Pauline; Allmer, Cristine; Brion, Annie; Ziesmer, Steven C.; Morschhauser, Franck; Habermann, Thomas M.; Gaillard, Isabelle; Link, Brian K.; Stamatoullas, Aspasia; Fermé, Christophe; Dogan, Ahmet; Macon, William R.; Audouin, Josée; Cerhan, James R.; Salles, Gilles

    2014-01-01

    Background Cytokines are important immune mediators of classical Hodgkin lymphoma (CHL) pathogenesis, and circulating levels at diagnosis may help predict prognosis. Germline single nucleotide polymorphisms (SNPs) in immune genes have been correlated with cytokine production and function. Methods We investigated whether selected germline SNPs in IL10 (rs1800890, rs1800896, rs1800871, rs1800872), TNFA (rs1800629), IL6 (rs1800795), ILRN (rs419598), INFG (rs2430561) and CCL17 (rs223828) were associated with circulating levels of related cytokines at diagnosis and progression-free survival (PFS) in CHL. Patients were from France (GELA, N = 464; median age = 32 years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N = 239; median age = 38 years); 22% of 346 CHL cases with EBV tumor status were positive. Results There was no association with any of the SNPs with cytokine levels. Overall, there was no association of any of the SNPs with PFS. In exploratory analyses by EBV status, TNFA rs1800629 (HRAA/AG = 2.41; 95%CI, 1.17–4.94) was associated with PFS in EBV-negative GELA patients, with similar trends in the SPORE patients (HRAA/AG = 1.63; 95%CI, 0.61–4.40). In a meta-analysis of the two studies, TNFA (HRAA/AG = 2.11; 95%CI, 1.18–3.77; P = 0.01) was statistically significant, and further adjustment for the international prognostic system did not alter this result. Conclusions This study showed that germline variation in TNFA was associated with CHL prognosis for EBV-negative patients, which will require confirmation. These results support broader studies on the differential impact of genetic variation in immune genes on EBV-positive vs. EBV-negative CHL pathogenesis. PMID:24008079

  17. Diffusion MR Characteristics Following Concurrent Radiochemotherapy Predicts Progression-Free and Overall Survival in Newly Diagnosed Glioblastoma

    PubMed Central

    Chang, Warren; Pope, Whitney B.; Harris, Robert J.; Hardy, Anthony J.; Leu, Kevin; Mody, Reema R.; Nghiemphu, Phioanh L.; Lai, Albert; Cloughesy, Timothy F.; Ellingson, Benjamin M.

    2015-01-01

    The standard of care for newly diagnosed glioblastoma (GBM) is surgery, then radiotherapy (RT) with concurrent temozolomide (TMZ), followed by adjuvant TMZ. We hypothesized patients with low diffusivity measured using apparent diffusion coefficient (ADC) histogram analysis evaluated after RT+TMZ, prior to adjuvant TMZ, would have a significantly shorter progression-free (PFS) and overall survival (OS). To test this hypothesis we evaluated 120 patients with newly diagnosed GBM receiving RT+TMZ followed by adjuvant TMZ. MRI was performed after completion of RT+TMZ, prior to initiation of adjuvant TMZ. A double Gaussian mixed model was used to describe the ADC histograms within the enhancing tumor, where ADCL and ADCH were defined as the mean ADC value of the lower and higher Gaussian distribution, respectively. An ADCL value of 1.0 um2/ms and ADCH value of 1.6 um2/ms were used to stratify patients into high and low risk categories. Results suggest patients with low ADCL had significantly shorter PFS (Cox Hazard Ratio = 0.12, P = 0.0006). OS was significantly shorter with low ADCL tumors, showing a median OS of 407 vs. 644 days (Cox Hazard Ratio = 0.31, P = 0.047). ADCH was not predictive of PFS or OS when accounting for age and ADCL. In summary, newly diagnosed glioblastoma patients with low ADCL after completion of RT+TMZ are likely to progress and die earlier than patients with higher ADCL. Results suggest ADC histogram analysis may be useful for patient risk stratification following completion of RT+TMZ. PMID:26740971

  18. Connexin 43 expression predicts poor progression-free survival in patients with non-muscle invasive urothelial bladder cancer

    PubMed Central

    Poyet, Cédric; Buser, Lorenz; Roudnicky, Filip; Detmar, Michael; Hermanns, Thomas; Mannhard, Doris; Höhn, Andrej; Rüschoff, Jan; Zhong, Qing; Sulser, Tullio; Moch, Holger; Wild, Peter J

    2015-01-01

    Objectives To evaluate the protein expression of connexin 43 (Cx43) in primary urothelial bladder cancer and test its association with the histopathological characteristics and clinical outcome. Methods A tissue microarray containing 348 tissue samples from 174 patients with primary urothelial carcinomas of the bladder was immunohistochemically stained for Cx43. The intensity of staining was semiquantitatively evaluated (score 0, 1+, 2+), and the association with clinicopathological features was assessed. Univariable and multivariable analyses were performed to identify predictors for progression-free survival (PFS). Results Membranous Cx43 immunoreactivity was detected in 118 (67.8%) of 174 analysable urothelial carcinomas, of which 31 (17.8%) showed even a strong (score 2+) and mainly homogeneous staining. Strong expression levels of Cx43 (score 2+) were associated with higher tumour grade, multiplicity and increased proliferation (all p<0.05). In the subgroup of patients with stage pTa and pT1 bladder tumours (n=158), strong Cx43 expression (p<0.001), solid growth pattern (p<0.001) and increased Ki-67 proliferation fraction (p<0.05) were significantly associated with shorter PFS in an univariable Cox regression analysis. In multivariable Cox regression models, Cx43 immunoreactivity and histological growth pattern remained highly significant and adverse risk factors for PFS. Conclusions The expression levels of Cx43 are frequent in non-muscle invasive bladder cancer (NMIBC), with high expression levels being associated with poor prognosis. Routine assessment of Cx43 expression may improve the identification of high-risk NMIBC. PMID:26251520

  19. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

    PubMed Central

    Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

    2014-01-01

    Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

  20. Six-month progression-free survival as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma patients receiving temozolomide.

    PubMed

    Polley, Mei-Yin C; Lamborn, Kathleen R; Chang, Susan M; Butowski, Nicholas; Clarke, Jennifer L; Prados, Michael

    2010-03-01

    We assessed six-month progression-free survival (PFS) as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ). A total of 183 patients with newly diagnosed GBM enrolled in 3 phase II protocols at the University of California-San Francisco were included. Patients were treated with interventions based on the Stupp regimen, each with the added component of a second oral agent given concurrently with radiotherapy and TMZ, followed by its coadministration with adjuvant TMZ. We examined whether progression status at 2, 4, and 6 months predicted subsequent survival using the landmark analysis. The hazard ratios of death as a function of progression status were estimated based on the Cox proportional hazards model after adjustment for putative prognostic factors. Progression status at 2, 4, and 6 months were all consistently found to be strong predictors of subsequent survival in all studies. The study-specific hazard ratios associated with progression status at 6 months ranged from 2.03 to 3.39. The hazard ratios associated with the earlier time points (2- and 4-month progression) all exceeded 2 in magnitude, ranging from 2.29 to 4.73. P-values were statistically significant for all time points. In this report, we demonstrated a strong association between the endpoints of PFS at 2, 4, and 6 months and survival. Patients who showed the signs of early progression were at significantly higher risk of earlier death. Our analysis suggests that 6-month PFS may be an appropriate primary endpoint in the context of phase II upfront GBM trials in the TMZ era. PMID:20167815

  1. Six-month progression-free survival as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma patients receiving temozolomide

    PubMed Central

    Polley, Mei-Yin C.; Lamborn, Kathleen R.; Chang, Susan M.; Butowski, Nicholas; Clarke, Jennifer L.; Prados, Michael

    2010-01-01

    We assessed six-month progression-free survival (PFS) as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ). A total of 183 patients with newly diagnosed GBM enrolled in 3 phase II protocols at the University of California–San Francisco were included. Patients were treated with interventions based on the Stupp regimen, each with the added component of a second oral agent given concurrently with radiotherapy and TMZ, followed by its coadministration with adjuvant TMZ. We examined whether progression status at 2, 4, and 6 months predicted subsequent survival using the landmark analysis. The hazard ratios of death as a function of progression status were estimated based on the Cox proportional hazards model after adjustment for putative prognostic factors. Progression status at 2, 4, and 6 months were all consistently found to be strong predictors of subsequent survival in all studies. The study-specific hazard ratios associated with progression status at 6 months ranged from 2.03 to 3.39. The hazard ratios associated with the earlier time points (2- and 4-month progression) all exceeded 2 in magnitude, ranging from 2.29 to 4.73. P-values were statistically significant for all time points. In this report, we demonstrated a strong association between the endpoints of PFS at 2, 4, and 6 months and survival. Patients who showed the signs of early progression were at significantly higher risk of earlier death. Our analysis suggests that 6-month PFS may be an appropriate primary endpoint in the context of phase II upfront GBM trials in the TMZ era. PMID:20167815

  2. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    PubMed Central

    Clarke†, Jennifer L.; Ennis†, Michele M.; Yung, W. K. Alfred; Chang, Susan M.; Wen, Patrick Y.; Cloughesy, Timothy F.; DeAngelis, Lisa M.; Robins, H. Ian; Lieberman, Frank S.; Fine, Howard A.; Abrey, Lauren; Gilbert, Mark R.; Mehta, Minesh; Kuhn, John G.; Aldape, Kenneth D.; Lamborn, Kathleen R.; Prados, Michael D.

    2011-01-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998–2005, 105 of whom had surgery (excluding biopsies) during the study or ≤30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005–2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment. PMID:21813511

  3. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    PubMed

    Clarke, Jennifer L; Ennis, Michele M; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; Deangelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Lamborn, Kathleen R; Prados, Michael D

    2011-10-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998-2005, 105 of whom had surgery (excluding biopsies) during the study or ≤ 30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005-2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment. PMID:21813511

  4. Progression-Free Survival as a Surrogate for Overall Survival in Advanced/Recurrent Gastric Cancer Trials: A Meta-Analysis

    PubMed Central

    Oba, Koji; Bang, Yung-Jue; Bleiberg, Harry; Boku, Narikazu; Bouché, Olivier; Catalano, Paul; Fuse, Nozomu; Michiels, Stefan; Moehler, Markus; Morita, Satoshi; Ohashi, Yasuo; Ohtsu, Atsushi; Roth, Arnaud; Rougier, Philippe; Sakamoto, Junichi; Sargent, Daniel; Sasako, Mitsuru; Shitara, Kohei; Thuss-Patience, Peter; Van Cutsem, Eric; Burzykowski, Tomasz; Buyse, Marc

    2013-01-01

    The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval [CI] = 0.852 to 0.854). The R 2 between treatment effects on PFS and on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were only moderately correlated, and we could not confirm the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cancer. PMID:24108811

  5. Cetuximab treatment for metastatic colorectal cancer with KRAS p.G13D mutations improves progression-free survival

    PubMed Central

    OSUMI, HIROKI; SHINOZAKI, EIJI; OSAKO, MASAHIKO; KAWAZOE, YOSHIMASA; OBA, MASARU; MISAKA, TAKAHARU; GOTO, TAKASHI; KAMO, HITOMI; SUENAGA, MITSUKUNI; KUMEKAWA, YOSUKE; OGURA, MARIKO; OZAKA, MASATO; MATSUSAKA, SATOSHI; CHIN, KEISHO; HATAKE, KIYOHIKO; MIZUNUMA, NOBUYUKI

    2015-01-01

    A number of previous studies have reported that 30–50% of patients with colorectal cancer (CRC) harbor Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, which is a major predictive biomarker of resistance to epidermal growth factor (EGFR)-targeted therapy. Treatment with an anti-EGFR inhibitor is recommended for patients with KRAS wild-type metastatic colorectal cancer (mCRC). A recent retrospective study of cetuximab reported that patients with KRAS p.G13D mutations had better outcomes compared with those with other mutations. The aim of this retrospective study was to assess the prevalence of KRAS p.G13D mutations and evaluate the effectiveness of cetuximab in mCRC patients with KRAS p.G13D or other KRAS mutations. We reviewed the clinical records of 98 mCRC patients with KRAS mutations who were treated between August, 2004 and January, 2011 in four hospitals located in Tokyo and Kyushu Island. We also investigated KRAS mutation subtypes and patient characteristics. In the patients who received cetuximab, univariate and multivariate analyses were performed to assess the effect of KRAS p.G13D mutations on progression-free survival (PFS) and overall survival (OS). Of the 98 patients, 23 (23.5%) had KRAS p.G13D-mutated tumors, whereas 75 (76.5%) had tumors harboring other mutations. Of the 31 patients who received cetuximab, 9 (29.0%) had KRAS p.G13D mutations and 22 (71.0%) had other mutations. There were no significant differences in age, gender, primary site, pathological type, history of chemotherapy, or the combined use of irinotecan between either of the patient subgroups. The univariate analysis revealed no significant difference in PFS or OS between the patients with KRAS p.G13D mutations and those with other mutations (median PFS, 4.5 vs. 2.8 months, respectively; P=0.65; and median OS, 15.3 vs. 8.9 months, respectively; P=0.51). However, the multivariate analysis revealed a trend toward better PFS among patients harboring p.G13D mutations (PFS

  6. Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma

    PubMed Central

    Agarwal, Neeraj; Bellmunt, Joaquim; Maughan, Benjamin L.; Boucher, Kenneth M.; Choueiri, Toni K.; Qu, Angela Q.; Vogelzang, Nicholas J.; Fougeray, Ronan; Niegisch, Guenter; Albers, Peter; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S.; Tantravahi, Srinivas K.; Galsky, Matthew D.; Petrylak, Daniel P.; Vaishampayan, Ulka N.; Mehta, Amitkumar N.; Beer, Tomasz M.; Sternberg, Cora. N.; Rosenberg, Jonathan E.; Sonpavde, Guru

    2014-01-01

    This study examined the association of progression-free survival at 6 months with overall survival in the context of second-line therapy of advanced urothelial carcinoma in pooled patient-level data from 10 phase II trials and then externally validated in a large phase III trial. Progression-free survival at 6 months was significantly correlated with overall survival and is an innovative primary endpoint to evaluate new agents in this setting. Objective Second-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents. Methods Ten second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction. Results In the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R2 = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R2 = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared PMID:24220220

  7. Interpreting overall survival results when progression-free survival benefits exist in today’s oncology landscape: a metastatic renal cell carcinoma case study

    PubMed Central

    Tang, Yiyun; Bycott, Paul; Åkerborg, Örjan; Jönsson, Linus; Negrier, Sylvie; Chen, Connie

    2014-01-01

    Background The debate surrounding the acceptance of progression-free survival (PFS) as an intermediate endpoint to overall survival (OS) has grown in recent years, due to the challenges in demonstrating an OS benefit within clinical trials today. PFS is generally a good predictor of OS for cases where survival post-progression (SPP) is short, and less so when SPP is long. SPP depends on multiple factors, including residual effect from experimental treatment and effect from crossover or other subsequent therapies, posing unique challenges into the translation of PFS benefit into OS. Methods The objective of this analysis was to conduct simulations investigating how increasing SPP impacts PFS translation to OS, utilizing data from the AXIS (axitinib versus sorafenib in advanced metastatic renal cell carcinoma) trial. The underlying assumption was a treatment benefit in PFS (the PFS distribution parameters were chosen to be equal to median PFS in the AXIS trial) but no treatment effect on SPP, implying that PFS improvement is directly reflected in OS improvement. Results The probability of a statistically significant difference between arms for OS decreased from 54.7% to 6.1% when median SPP was increased from one to 20 months. The probability of the hazard ratio of OS being ≥0.9 was similarly increased from 24.3% to 72.6%, even though the hazard ratio for PFS was 0.69. Conclusion The present study shows that when simulated SPP is added to trial PFS data, the existing PFS benefit is diluted. Knowing that the AXIS treatment arms are well balanced with respect to post-trial treatments, we conclude that the PFS to OS benefit translation is primarily obscured by random variability largely unrelated to the true outcomes. The implications for drug development are not insignificant, as there would be a need to include more patients in studies or utilize a longer follow-up time to overcome the SPP variability issue. PMID:25278784

  8. Evaluation of progression-free survival as a surrogate endpoint for survival in chemotherapy and targeted agent metastatic colorectal cancer trials.

    PubMed

    Sidhu, Roger; Rong, Alan; Dahlberg, Steve

    2013-03-01

    Pooled analyses of chemotherapy trials in metastatic colorectal cancer (mCRC) have suggested that progression-free survival (PFS) is a surrogate endpoint for overall survival (OS). However, this has not been evaluated under current standard-of-care regimens of chemotherapy in combination with targeted therapies. We conducted an analysis of published mCRC trials of chemotherapy and targeted therapies from 2000 to evaluate the surrogacy of PFS and response rate (RR) for OS. Study-level data was pooled from 24 randomized mCRC trials that evaluated fluoropyrimidine-based regimens and included trials conducted with targeted agents (panitumumab, cetuximab, bevacizumab, and aflibercept). A total of 69 treatment arms with a sample size of 20,438 patients was included. Linear regression analysis was carried out to estimate the correlation of PFS and RR with OS. The correlation coefficient between PFS HRs and OS HRs was 0.86 for all trials, 0.89 for 12 phase III trials of targeted agents in combination with chemotherapy, 0.95 for 8 first-line phase III trials of targeted agents, and 0.83 for 9 trials of anti-EGFR-targeted agents. In all cases, correlation coefficients between RR and OS HRs were lower than those between PFS HRs and OS HRs (range, 0.42-0.81). In this study-level analysis of randomized mCRC trials of chemotherapy and targeted agents, improvements in PFS are strongly correlated with improvements in OS. This suggests that PFS remains a valid surrogate endpoint for OS with current treatment regimens in the mCRC setting. PMID:23303214

  9. Progression-free survival as a surrogate endpoint for overall survival in patients with third-line or later-line chemotherapy for advanced gastric cancer

    PubMed Central

    Liu, Liya; Yu, Hao; Huang, Lihong; Shao, Fang; Bai, Jianling; Lou, Donghua; Chen, Feng

    2015-01-01

    Background The correlation between overall survival (OS) and progression-free survival (PFS) has been evaluated in patients with metastatic or advanced gastric cancer who have received first-line and/or second-line chemotherapy. However, no corresponding analysis has been done for patients who have undergone third-line or later-line chemotherapy. Methods A total of 303 patients from the Phase II/III studies of apatinib were pooled (the Phase II study as a training data set, the Phase III study as a testing data set). Landmark analyses of PFS at 2 months from randomization were performed to minimize lead time bias. The Cox proportional hazard model was used to test for the significance effect of PFS rate at 2 months in predicting OS. Additionally, the PFS/OS correlations were evaluated by the normal induced copula (National Institute for Health and Care Excellence) estimation model. Results The median OS was 3.37 months (95% confidence interval 2.63–3.80) in patients who experienced progression at 2 months and 5.67 months in patients who did not (95% confidence interval 4.83–6.67; P<0.0001). Compared with patients who did not progress at 2 months, the adjusted hazard ratio for death was 3.39 (95% confidence interval 1.79–6.41; P<0.0001) for patients who experienced progression at 2 months. Moreover, the correlation of PFS/OS was 0.84 (95% confidence interval 0.74–0.90). Similar results were found in the testing data set. Conclusion These results indicate that PFS correlates strongly with OS, suggesting PFS may be a useful early endpoint for patients with advanced gastric cancer who have undergone third-line or later-line chemotherapy. These observations require prospective validation. PMID:25960663

  10. Increased C-kit intensity is a poor prognostic factor for progression-free and overall survival in patients with newly diagnosed AML.

    PubMed

    Advani, Anjali S; Rodriguez, Cristina; Jin, Tao; Jawde, Rony Abou; Saber, Wael; Baz, Rachid; Kalaycio, Matt; Sobecks, Ronald; Sekeres, Mikkael; Tripp, Barbara; Hsi, Eric

    2008-06-01

    C-kit, a tyrosine kinase receptor, is expressed on most myeloid blasts and is thought to be important in the pathogenesis of AML. Activation of the c-kit receptor leads to phosphorylation and activation of downstream signaling proteins, which are important for cell survival and proliferation. Here, we discuss the prognostic impact of c-kit intensity, measured using the mean fluorescent index (MFI) in patients with newly diagnosed AML. On multivariate analysis, c-kit MFI>20.3 correlated with a decreased progression-free survival and overall survival, independent of known prognostic factors (age, white blood count at diagnosis and cytogenetics). Whether inhibiting c-kit in patients with AML will alter prognosis is the basis of ongoing clinical trials. PMID:17928050

  11. Systematic CpG Islands Methylation Profiling of Genes in the Wnt Pathway in Epithelial Ovarian Cancer Identifies Biomarkers of Progression-Free Survival

    PubMed Central

    Dai, Wei; Teodoridis, Jens M.; Zeller, Constanze; Graham, Janet; Hersey, Jenny; Flanagan, James M.; Stronach, Euan; Millan, David W.; Siddiqui, Nadeem; Paul, Jim; Brown, Robert

    2011-01-01

    Purpose Wnt pathways control key biological processes that potentially impact on tumour progression and patient survival. We aimed to evaluate DNA methylation at promoter CpG islands (CGIs) of Wnt pathway genes in ovarian tumours at presentation and identify biomarkers of patient progression-free survival (PFS). Experimental Design Epithelial ovarian tumours (screening study n=120, validation study n=61) prospectively collected through a cohort study, were analysed by differential methylation hybridisation (DMH) at 302 loci spanning 189 promoter CGIs at 137 genes in Wnt pathways. The association of methylation and progression free survival was examined by Cox proportional hazards model. Results DNA methylation is associated with PFS at 20/302 loci (p<0.05, n=111), with 5 loci significant at FDR<10%. 11/20 loci retain significance in an independent validation cohort (n=48,p≤0.05,FDR≤10%), and 7 of these loci, at FZD4, DVL1, NFATC3, ROCK1, LRP5, AXIN1 and NKD1 genes, are independent from clinical parameters (adjusted p<0.05). Increased methylation at these loci associates with increased hazard of disease progression. A multivariate Cox model incorporates only NKD1 and DVL1, identifying two groups differing in PFS (HR=2.09; 95%CI (1.39, 3.15); permutation test p<0.005). Methylation at DVL1 and NFATC3 show significant association with response. Consistent with their epigenetic regulation, reduced expression of FZD4, DVL1 and ROCK1 is an indicator of early disease relapse in an independent ovarian tumour cohort (n=311, adjusted p<0.05). Conclusions The data highlights the importance of epigenetic regulation of multiple promoter CGIs of Wnt pathway genes in ovarian cancer and identifies methylation at NKD1 and DVL1 as independent predictors of PFS. PMID:21459799

  12. Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2 immunotherapy and isotretinoin: a prospective Phase II study

    PubMed Central

    Kushner, Brian H; Ostrovnaya, Irina; Cheung, Irene Y; Kuk, Deborah; Kramer, Kim; Modak, Shakeel; Yataghene, Karima; Cheung, Nai-Kong V

    2015-01-01

    Relapse of high-risk neuroblastoma (HR-NB) is deemed invariably fatal yet increasing numbers of HR-NB patients achieve a second complete/very good partial remission (CR/VGPR), hence the urgency to find a successful consolidative therapy. Identifying efficacy in patients without assessable disease, however, is problematic. We report the first study providing outcome data for this group of patients with poor prognosis. To prevent another relapse, HR-NB patients in second or later CR/VGPR received the anti-GD2 murine antibody 3F8 plus granulocyte-macrophage colony-stimulating factor plus isotretinoin in a Phase II trial. Upon meeting the target aim for progression-free survival (PFS) in the initial cohort of 33 patients, the trial was amended to allow patients who developed human anti-mouse antibody (HAMA) to receive rituximab to ablate HAMA with or without low-dose maintenance chemotherapy until immunotherapy could resume. For the total of 101 study patients, 5-year PFS and overall survival (OS) rates were 33% ± 5% and 48% ± 5%, respectively. Among the 33 long-term progression-free survivors, 19 had MYCN amplification, 19 had previously received anti-GD2 immunotherapy plus isotretinoin (as first-line therapy), and 15 never received maintenance chemotherapy. In a multivariate analysis of prognostic factors, only absence of minimal residual disease in bone marrow after 2 cycles of immunotherapy and before initiation of isotretinoin or anti-HAMA therapy was significantly favorable for both PFS and OS. Therefore, long-term PFS is possible for HR-NB patients who achieve at least a second CR/VGPR and receive consolidation that includes anti-GD2 immunotherapy plus isotretinoin, even if the patients received these biological treatments before relapse. Results from this prospective study will aid in the development of future Phase II studies for this growing ultra high-risk patient population. PMID:26140243

  13. {sup 18}Fluorodeoxyglucose PET Is Prognostic of Progression-Free and Overall Survival in Locally Advanced Pancreas Cancer Treated With Stereotactic Radiotherapy

    SciTech Connect

    Schellenberg, Devin; Quon, Andy; Minn, A. Yuriko; Graves, Edward E.; Kunz, Pamela; Ford, James M.; Fisher, George A.; Goodman, Karyn A.; Koong, Albert C.; Chang, Daniel T.

    2010-08-01

    Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.

  14. Treatment of Metastatic Breast Cancer in a Real-World Scenario: Is Progression-Free Survival With First Line Predictive of Benefit From Second and Later Lines?

    PubMed Central

    Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Minisini, Alessandro Marco; Rihawi, Karim; Fasola, Gianpiero

    2015-01-01

    Introduction. Despite the availability of several therapeutic options for metastatic breast cancer (MBC), no robust predictive factors are available to help clinical decision making. Nevertheless, a decreasing benefit from first line to subsequent lines of treatment is commonly observed. The aim of this study was to assess the impact of benefit from first-line therapy on outcome with subsequent lines. Methods. We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) between 2004 and 2012. We evaluated progression-free survival (PFS) at first (PFS1), second, third, and fourth therapeutic lines, according to treatment (ET and/or CT) and tumor subtypes. Results. In the whole cohort, median overall survival was 34 months, and median PFS1 was 9 months. A 6-month benefit was shown by 289 patients (63.5%) at first line, 128 (40.5%) at second line, 76 (33.8%) at third line, and 34 (23.3%) at fourth line. Not having a 6-month benefit at PFS1 was associated with less chance of benefit at second line (odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.29–0.77, p = .0026) and at any line beyond first (OR: 0.39; 95% CI: 0.24–0.62, p < .0001). In the total series, after stratification for tumor subtypes, a strong predictive effect was observed among HER2-positive tumors (OR: 0.2; 95% CI: 0.05–0.73, p = .0152). Conclusion. Our results suggest that the absence of at least a 6-month benefit in terms of PFS with first-line therapy predicts a reduced probability of benefit from subsequent therapeutic lines, especially in HER2-positive disease. Implications for Practice: This study supports evidence showing that the absence of a 6-month benefit in terms of progression-free survival with first-line therapy predicts a lack of benefit from subsequent therapeutic lines in metastatic breast cancer. The random distribution of benefit experienced by a subset of the cohort further spurs an interest in identifying predictive

  15. Clinical Significance of the Relationship between Progression-Free Survival or Postprogression Survival and Overall Survival in Patients with Extensive Disease-Small-Cell Lung Cancer Treated with Carboplatin plus Etoposide

    PubMed Central

    Imai, Hisao; Mori, Keita; Watase, Nodoka; Fujimoto, Sakae; Kaira, Kyoichi; Yamada, Masanobu; Minato, Koichi

    2016-01-01

    Background. The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small-cell lung cancer (SCLC). Therefore, by using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) or postprogression survival (PPS) and OS after first-line chemotherapies in patients with extensive disease-SCLC (ED-SCLC) treated with carboplatin plus etoposide. Methods. Between July 1998 and December 2014, we analyzed 63 cases of patients with ED-SCLC who were treated with carboplatin and etoposide as first-line chemotherapy. The relationships of PFS and PPS with OS were analyzed at the individual level. Results. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.90, p < 0.05, and R2 = 0.71) and PFS was moderately correlated with OS (r = 0.72, p < 0.05, and R2 = 0.62). Type of relapse (refractory/sensitive) and the number of regimens administered after disease progression after the first-line chemotherapy were both significantly associated with PPS (p < 0.05). Conclusions. PPS has a stronger relationship with OS than does PFS in ED-SCLC patients who have received first-line chemotherapy. These results suggest that treatments administered after first-line chemotherapy affect the OS of ED-SCLC patients treated with carboplatin plus etoposide. PMID:27445549

  16. Progression-free and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone acetate can be predicted with serial C11-acetate PET/CT

    PubMed Central

    Farnebo, Jacob; Wadelius, Agnes; Sandström, Per; Nilsson, Sten; Jacobsson, Hans; Blomqvist, Lennart; Ullén, Anders

    2016-01-01

    Abstract In this retrospective study, we evaluated the benefit of repeated carbon 11 (C11)-acetate positron emission tomography/computed tomography (PET/CT) to assess response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). A total of 30 patients with mCRPC were monitored with C11-acetate PET/CT and PSA levels during their treatment with AA. Retrospective evaluation of their response was made after 102 days (median; range 70–155) of treatment. Statistical analyses were employed to detect predictors of progression-free survival (PFS) and overall survival (OS), and potential correlation between serum levels of PSA, standardized uptake values (SUVpeak), and bone lesion index measured from PET were investigated. At follow-up 10 patients exhibited partial response (PR), 10 progressive disease (PD), and 10 stable disease (SD), as assessed by PET/CT. In survival analysis, both PR and PD were significantly associated with PFS and OS. CT response was also associated with OS, but only 19/30 patients demonstrated a lesion meeting target lesion criteria according to RECIST 1.1. No PET/CT baseline characteristic was significantly associated with PFS or OS. A PSA response (reduction in the level by >50%) could also predict PFS and OS. In the subgroup lacking a PSA response, those with PD had significantly shorter OS than those with PR or SD. PFS and OS in patients with mCRPC treated with AA can be predicted from repeated C11-acetate PET/CT. This may be of particular clinical value in patients who do not exhibit a PSA response to treatment. PMID:27495034

  17. Progression-free and overall survival in patients with recurrent Glioblastoma multiforme treated with last-line bevacizumab versus bevacizumab/lomustine.

    PubMed

    Heiland, D H; Masalha, W; Franco, P; Machein, M R; Weyerbrock, A

    2016-02-01

    Bevacizumab (BEV) is widely used for treatment of patients with recurrent glioblastoma multiforme (GBM). 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU, lomustine) monotherapy is an approved chemotherapeutical option for recurrent GBM. Recent evidence demonstrated a survival benefit of combined treatment with BEV and CCNU in patients with a first recurrence of GBM. We examined the outcome of recurrent GBM patients with BEV monotherapy versus BEV/CCNU therapy when used as last-line therapy. 35 patients with recurrent GBM treated between 2010 and 2014 were included in this retrospective study. Progression-free and overall survival was determined with reference to the beginning of BEV or BEV/CCNU therapy and initial diagnosis. 17 patients received BEV monotherapy, 18 patients received combined BEV and CCNU therapy. The impact of parameters such as IDH mutation, MGMT promoter methylation, tumor localization, histology and the number of surgeries were included in a multivariate ANOVA analysis. Furthermore, Karnofsky performance score (KPS), neurological function and toxicity were assessed. BEV/CCNU treatment led to an extension of PFS (6.11 months; 95% CL 3.41-12.98 months; log-rank p = 0.00241) and OS (6.59 months; 95% CL 5.51-16.3 months; log-rank p = 0.0238) of 2 months compared to BEV monotherapy. This survival advantage was independent of histology, IDH mutation status or the number of previous surgeries. Neurological function, KPS and toxicity were not significantly different between both treatment groups. Last-line therapy with BEV/CCNU results in a longer PFS and OS compared to BEV monotherapy and is well-tolerated. These findings confirm the role of these agents in the treatment of recurrent GBM and are in line with other studies. PMID:26614518

  18. Factors that predict progression-free survival in Chinese lung adenocarcinoma patients treated with epidermal growth factor receptor tyrosine kinase inhibitors

    PubMed Central

    Cui, Shaohua; Xiong, Liwen; Lou, Yuqing; Shi, Huangping; Gu, Aiqin; Zhao, Yizhuo; Chu, Tianqing; Wang, Huimin; Zhang, Wei; Dong, Lili

    2016-01-01

    Background Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown efficacy in patients with advanced lung cancers, survival predictors with these drugs have not been extensively investigated. This study was performed to explore factors that may predict progression-free survival (PFS) in Chinese lung adenocarcinoma patients treated with EGFR-TKIs. Methods We retrospectively collected clinicopathologic data on 208 patients who received either gefitinib, erlotinib or icotinib, including the patients’ EGFR mutation status and levels of six serum tumor markers [carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCC), cytokeratin-19 fragments (CYFRA21-1) and lactate dehydrogenase (LDH)]. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with PFS. Results At the study cutoff date, 189 (90.9%) of the patients met the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria for progressive disease (PD), while 19 (9.1%) had stable disease (SD). The median PFS of the 208 patients was 12.4 months (95% CI, 11.0–13.8 months). In the multivariate analysis using a Cox proportional hazard model, a non-smoking history [hazard ratio (HR) =2.460; 95% CI, 1.484–4.079; P<0.001], first-line treatment (HR =1.500; 95% CI, 1.062–2.119; P=0.021), and a high pretreatment serum level of CEA (HR =1.424; 95% CI 1.026–1.977; P=0.035) were found to be significant predictors of a longer PFS. Conclusions In Chinese lung adenocarcinoma patients treated with EGFR-TKIs, a non-smoking history, first-line EGFR-TKIs treatment and a high serum level of CEA were independent predictors of a longer PFS along with an EGFR-activating mutation. PMID:26904214

  19. GSTP1 Ile105Val polymorphism correlates with progression-free survival in MCRC patients treated with or without irinotecan: a study of the Dutch Colorectal Cancer Group

    PubMed Central

    Kweekel, D M; Koopman, M; Antonini, N F; Van der Straaten, T; Nortier, J W R; Gelderblom, H; Punt, C J A; Guchelaar, H-J

    2008-01-01

    A Valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity. As nuclear GSTP1 activity decreases irinotecan cytotoxicity, Val-allele carriers may benefit more from irinotecan chemotherapy. Our aim was to investigate the association of GSTP1 genotype with treatment outcome of irinotecan. Progression-free survival (PFS) and toxicity were determined in 267 metastatic colorectal cancer (MCRC) patients who were treated with first-line capecitabine (CAP) plus irinotecan (CAPIRI), or CAP single agent in a prospective randomised phase III trial (CAIRO). GSTP1 genotype was determined by Pyrosequencing. Patients receiving CAP showed a PFS of 6.6 (Ile/Ile), 6.0 (Ile/Val) and 6.5 months (Val/Val); compared to 7.0 (Ile/Ile), 8.8 (Ile/Val) and 9.2 months (Val/Val) with CAPIRI. Median PFS was 2.7 months longer in Val-allele carriers treated with CAPIRI compared to CAP (P=0.005). Patients with the Ile/Ile genotype showed similar PFS with CAPIRI and CAP (7.0 compared to 6.6 months, P=0.972). Toxicity did not differ significantly among genotypes. GSTP1 codon 105 polymorphism may be predictive for the response to irinotecan-based chemotherapy in patients with MCRC, with the Val-allele being associated with a better outcome. Ile/Ile genotype patients do not appear to benefit from the addition of irinotecan to CAP. PMID:18797455

  20. Lower expression of activating transcription factors 3 and 4 correlates with shorter progression-free survival in multiple myeloma patients receiving bortezomib plus dexamethasone therapy

    PubMed Central

    Narita, T; Ri, M; Masaki, A; Mori, F; Ito, A; Kusumoto, S; Ishida, T; Komatsu, H; Iida, S

    2015-01-01

    Bortezomib (BTZ), a proteasome inhibitor, is widely used in the treatment of multiple myeloma (MM), but a fraction of patients respond poorly to this agent. To identify factors predicting the duration of progression-free survival (PFS) of MM patients on BTZ treatment, the expression of proteasome and endoplasmic reticulum (ER) stress-related genes was quantified in primary samples from patients receiving a combination of BTZ and dexamethasone (BD). Fifty-six MM patients were stratified into a group with PFS<6 months (n=33) and a second group with PFS⩾6 months (n=23). Of the 15 genes analyzed, the expression of activating transcription factor 3 (ATF3) and ATF4 was significantly lower in patients with shorter PFS (P=0.0157 and P=0.0085, respectively). Chromatin immunoprecipitation analysis showed that these ATFs bind each other and transactivate genes encoding the pro-apoptotic transcription factors, CHOP and Noxa, which promote ER stress-associated apoptosis. When either ATF3 or ATF4 expression was silenced, MM cells partially lost sensitivity to BTZ treatment. This was accompanied by lower levels of Noxa, CHOP and DR5. Thus low basal expression of ATF3 and ATF4 may attenuate BTZ-induced apoptosis. Hence, ATF3 and ATF4 could potentially be used as biomarkers to predict efficacy of BD therapy in patients with MM. PMID:26636288

  1. Prediction of biomarkers of therapeutic effects of patients with lung adenocarcinoma treated with gefitinib based on progression-free-survival by metabolomic fingerprinting.

    PubMed

    Zhuang, Jingcong; Tang, Xiaohu; Du, Zhenxia; Yang, Ming; Zhou, Ying

    2016-11-01

    Lung carcinoma is one of the most frequently diagnosed malignancy and threats human life and health. In clinical practice, gefitinib, one of the most well-known epidermal growth factor receptor tyrosine kinase inhibitors, was frequently used in the treatment of non-small cell lung carcinoma. However, this drug is not useful for all non-small cell patients. In this study, the biomarkers were found out to predict the therapeutic effects of gefitinib for lung carcinoma patients. Serum samples were collected from patients with advanced lung adenocarcinoma. The ultra-high performance liquid chromatography (UHPLC)-quadrupole-time of flight mass spectrometry (Q-TOF MS) was conducted to obtain the metabolic data for each patient. Partial least squares-discriminate analysis (PLS-DA) was performed to indicate the differences between metabolites of patients, and Cox proportional hazards regression analysis was used to eliminate the interference of the patient's gender, age, smoking history and disease stage. Thus, differential biomarkers were found. The combination of these biomarkers was statistically significant predictors based on progression-free survival. If these biomarkers can be further confirmed by the clinic, it could suggest the proper therapeutic schedule, and help to reduce patients' economic burden and medication side effects. PMID:27591660

  2. Expression signature distinguishing two tumour transcriptome classes associated with progression-free survival among rare histological types of epithelial ovarian cancer

    PubMed Central

    Wang, Chen; Winterhoff, Boris J; Kalli, Kimberly R; Block, Matthew S; Armasu, Sebastian M; Larson, Melissa C; Chen, Hsiao-Wang; Keeney, Gary L; Hartmann, Lynn C; Shridhar, Viji; Konecny, Gottfried E; Goode, Ellen L; Fridley, Brooke L

    2016-01-01

    Background: The mechanisms of recurrence have been under-studied in rare histologies of invasive epithelial ovarian cancer (EOC) (endometrioid, clear cell, mucinous, and low-grade serous). We hypothesised the existence of an expression signature predictive of outcome in the rarer histologies. Methods: In split discovery and validation analysis of 131 Mayo Clinic EOC cases, we used clustering to determine clinically relevant transcriptome classes using microarray gene expression measurements. The signature was validated in 967 EOC tumours (91 rare histological subtypes) with recurrence information. Results: We found two validated transcriptome classes associated with progression-free survival (PFS) in the Mayo Clinic EOC cases (P=8.24 × 10−3). This signature was further validated in the public expression data sets involving the rare EOC histologies, where these two classes were also predictive of PFS (P=1.43 × 10−3). In contrast, the signatures were not predictive of PFS in the high-grade serous EOC cases. Moreover, genes upregulated in Class-1 (with better outcome) were showed enrichment in steroid hormone biosynthesis (false discovery rate, FDR=0.005%) and WNT signalling pathway (FDR=1.46%); genes upregulated in Class-2 were enriched in cell cycle (FDR=0.86%) and toll-like receptor pathways (FDR=2.37%). Conclusions: These findings provide important biological insights into the rarer EOC histologies that may aid in the development of targeted treatment options for the rarer histologies. PMID:27253175

  3. Radiographic Progression-Free Survival As a Response Biomarker in Metastatic Castration-Resistant Prostate Cancer: COU-AA-302 Results

    PubMed Central

    Morris, Michael J.; Molina, Arturo; Small, Eric J.; de Bono, Johann S.; Logothetis, Christopher J.; Fizazi, Karim; de Souza, Paul; Kantoff, Philip W.; Higano, Celestia S.; Li, Jinhui; Kheoh, Thian; Larson, Steven M.; Matheny, Shannon L.; Naini, Vahid; Burzykowski, Tomasz; Griffin, Thomas W.; Scher, Howard I.; Ryan, Charles J.

    2015-01-01

    Purpose Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC. Patients and Methods rPFS was defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation. Results A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P < .001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P < .001 and HR, 0.53; 95% CI, 0.45 to 0.62; P < .001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72. Conclusion rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials. PMID:25624432

  4. Bortezomib-based induction improves progression-free survival of myeloma patients harboring 17p deletion and/or t(4;14) and overcomes their adverse prognosis.

    PubMed

    El-Ghammaz, Amro M S; Abdelwahed, Essam

    2016-08-01

    Providing a risk-adapted treatment strategy has been a key goal in the ongoing research efforts aimed at providing treatment tailored to the individual genetic make-up. Eighty myeloma patients have been tested for presence of 17p deletion and/or t(4;14) by fluorescent in situ hybridization (FISH). Based on FISH results, they have been categorized into patients lacking them (standard risk) and those harboring them (high risk). Patients in each category were randomly assigned 1:1 to induction treatment by either vincristine, adriamycin and dexamethasone (VAD), or bortezomib and dexamethasone (VD) followed by autologous stem cell transplantation and thalidomide maintenance and were followed up for 32 months. 32.5 % of patients were high risk. Following induction, there were significantly higher rates of at least very good partial response achievement in VD arms in standard- and high-risk patients. Regarding complete response achievement, there were insignificant differences between VAD and VD arms in standard and high-risk patients. After a median follow-up of 17.5 months, there was insignificant difference in overall survival (OS) between VAD and VD arms in standard and high-risk patients. There was superior progression-free survival (PFS) in VD arms in standard- and high-risk patients. Among patients who received VD, those belonging to standard and high-risk groups had similar PFS. In conclusion, bortezomib-based induction is superior to non-bortezomib-based one in patients harboring 17p deletion and/or t(4;14) in terms of improving PFS but not OS. Also, it reduces progression risk in patients harboring these high risk cytogenetics. PMID:27184486

  5. Microwave ablation plus chemotherapy improved progression-free survival of advanced non-small cell lung cancer compared to chemotherapy alone.

    PubMed

    Wei, Zhigang; Ye, Xin; Yang, Xia; Huang, Guanghui; Li, Wenhong; Wang, Jiao; Han, Xiaoying

    2015-02-01

    The aim of the study was to determine survival benefit of the microwave ablation (MWA)/chemotherapy combination compared with chemotherapy alone. Patients with untreated, stage IIIB or IV NSCLC and at least one additional measurable site other than the ablative site were enrolled. They were divided into MWA/chemotherapy group and chemotherapy group. The primary endpoint was progression-free survival (PFS); secondary endpoints included response, time to local progression (TTLP), overall survival (OS), and adverse events (AEs). Forty-six and twenty-eight patients were enrolled in the MWA/chemotherapy group and chemotherapy group, respectively. Complete ablation was observed in 84.8 % patients in the MWA/chemotherapy group. Median TTLP was 27.0 months. Objective response rate and disease control rate in MWA/chemotherapy group were 21.7 and 76.1 %, and in the chemotherapy group were 32.1 % (p = 0.320) and 75.0 % (p = 0.916), respectively. MWA/chemotherapy combination prolonged PFS [MWA/chemotherapy group 10.9 (95 % CI 5.1-16.7) ms vs. chemotherapy group 4.8 (95 % CI 3.9-5.8) ms, p = 0.001] and tended to improve OS [MWA/chemotherapy group 23.9 (95 % CI 15.2-32.6) ms vs. chemotherapy group 17.3 (95 % CI 15.2-19.3) ms, p = 0.140]. Multivariate analyses showed that MWA was an independent prognostic factor of PFS and primary tumor size was an independent prognostic factor of OS. AEs of MWA were observed in 67.4 % patients. Chemotherapy-associated AEs were observed in 39.1 and 53.6 % of patients in the MWA/chemotherapy and chemotherapy group, respectively. MWA/chemotherapy combination improved PFS of advanced NSCLC compared to chemotherapy alone, and the combination did not increase the adverse events of chemotherapy. PMID:25572816

  6. Piwil 2 Expression Is Correlated with Disease-Specific and Progression-Free Survival of Chemotherapy-Treated Bladder Cancer Patients

    PubMed Central

    Taubert, Helge; Wach, Sven; Jung, Rudolf; Pugia, Michael; Keck, Bastian; Bertz, Simone; Nolte, Elke; Stoehr, Robert; Lehmann, Jan; Ohlmann, Carsten-H; Stöckle, Michael; Wullich, Bernd; Hartmann, Arndt

    2015-01-01

    Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The expression of Piwil 2 is associated with stem cells. A role in tumorigenesis and/or tumor progression is proposed for different cancers but not yet for bladder cancer (BCa). We investigated Piwil 2 expression by immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and adjuvant chemotherapy. The association between Piwil 2 expression and disease-specific (DSS) or progression-free survival (PFS) was calculated using Kaplan-Meier analyses and univariate/multivariate Cox regression hazard models. In a multivariate Cox regression analysis, Piwil 2 expression, either in the cytoplasm or the nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic staining pattern was associated with poor DSS and tumor progression (relative risk [RR] = 2.7, P = 0.004, and RR = 2.4, P = 0.027). Likewise, absent nuclear Piwil 2 immunoreactivity was associated with poor DSS and tumor progression (RR = 2.3, P = 0.023, and RR = 2.2, P = 0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related death (P = 0.005) compared with patients with strong expression. Considering only patients with high-grade G3 tumors, a 7.8-fold risk of tumor-associated death and a 3.6-fold risk of tumor progression were detected independently of the histologic tumor subtype or the chemotherapy regimen. In summary, a combination of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly associated with an increased risk of DSS and tumor progression. This indicates that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients. PMID:25998509

  7. The Prognostic Value of the Tumor Shrinkage Rate for Progression-Free Survival in Patients with Non-Small Cell Lung Cancer Receiving Gefitinib

    PubMed Central

    Park, Dong Il; Kim, Sun Young; Kim, Ju Ock; Jung, Sung Soo; Park, Hee Sun; Moon, Jae Young; Chung, Chae Uk; Kim, Song Soo; Seo, Jae Hee

    2015-01-01

    Background The efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy can be measured based on the rate of treatment response, based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria or progression-free survival (PFS). However, there are some patients harboring sensitive EGFR mutations who responded poorly to EGFR-TKI therapy. In addition, there is variability in the PFS after EGFR-TKI treatment. Methods We performed a retrospective analysis of the medical records of 85 patients with non-small cell lung cancer, who had achieved a stable disease or better response at the first evaluation of treatment response, after receiving a 2-month course of gefitinib. We calculated the tumor shrinkage rate (TSR) by measuring the longest and perpendicular diameter of the main mass on computed tomography before, and 2 months after, gefitinib therapy. Results There was a significant positive correlation between the TSR and PFS (R=0.373, p=0.010). In addition, a simple linear regression analysis showed that the TSR might be an indicator for the PFS (B±standard error, 244.54±66.79; p=0.001). On univariate analysis, the sex, histologic type, smoking history and the number of prior chemotherapy regimens, were significant prognostic factors. On multivariate regression analysis, both the TSR (β=0.257, p=0.029) and adenocarcinoma (β=0.323, p=0.005) were independent prognostic factors for PFS. Conclusion Our results showed that the TSR might be an early prognostic indicator for PFS in patients receiving EGFR-TKI therapy. PMID:26508917

  8. Establishing the Quantitative Relationship Between Lanreotide Autogel®, Chromogranin A, and Progression-Free Survival in Patients with Nonfunctioning Gastroenteropancreatic Neuroendocrine Tumors.

    PubMed

    Buil-Bruna, Núria; Dehez, Marion; Manon, Amandine; Nguyen, Thi Xuan Quyen; Trocóniz, Iñaki F

    2016-05-01

    The objective of this work was to establish the quantitative relationship between Lanreotide Autogel® (LAN) on serum chromogranin A (CgA) and progression-free survival (PFS) in patients with nonfunctioning gastroenteropancreatic neuroendocrine tumors (GEP-NETs) through an integrated pharmacokinetic/pharmacodynamic (PK/PD) model. In CLARINET, a phase III, randomized, double-blind, placebo-controlled study, 204 patients received deep subcutaneous injections of LAN 120 mg (n = 101) or placebo (n = 103) every 4 weeks for 96 weeks. Data for 810 LAN and 1298 CgA serum samples (n = 632 placebo and n = 666 LAN) were used to develop a parametric time-to-event model to relate CgA levels and PFS (76 patients experienced disease progression: n = 49 placebo and n = 27 LAN). LAN serum profiles were described by a one-compartment disposition model. Absorption was characterized by two parallel pathways following first- and zero-order kinetics. As PFS data were considered informative dropouts, CgA and PFS responses were modeled jointly. The LAN-induced decrease in CgA levels was described by an inhibitory E MAX model. Patient age and target lesions at baseline were associated with an increment in baseline CgA. Weibull model distribution showed that decreases in CgA from baseline reduced the hazard of disease progression significantly (P < 0.001). Covariates of tumor location in the pancreas and tumor hepatic tumor load were associated with worse prognosis (P < 0.001). We established a semimechanistic PK/PD model to better understand the effect of LAN on a surrogate endpoint (serum CgA) and ultimately the clinical endpoint (PFS) in treatment-naive patients with nonfunctioning GEP-NETs. PMID:26908127

  9. Quantitative Targeted Proteomics of Pancreatic Cancer: Deoxycytidine Kinase Protein Level Correlates to Progression-Free Survival of Patients Receiving Gemcitabine Treatment.

    PubMed

    Ohmine, Ken; Kawaguchi, Kei; Ohtsuki, Sumio; Motoi, Fuyuhiko; Ohtsuka, Hideo; Kamiie, Junichi; Abe, Takaaki; Unno, Michiaki; Terasaki, Tetsuya

    2015-09-01

    The purpose of the present study is to identify the determinant(s) of gemcitabine (dFdC)-sensitivity in pancreatic cancer tissues of patients treated with dFdC alone and in pancreatic cancer cell lines exposed to dFdC in vitro. Protein expression levels of 12 enzymes and 13 transporters potentially involved in transport and metabolism of dFdC in pancreatic cancer cell lines and tissues were quantified by means of our LC-MS/MS-based quantitative targeted proteomics technology. Protein expression levels of deoxycytidine kinase (dCK), uridine monophosphate-cytidine monophosphate (UMP-CMP) kinase, cytosolic nucleotidase III (cN-III), and equilibrative nucleoside transporter 1 (ENT1) were significantly correlated with IC50 or 1/IC50 in five cell lines with different sensitivities to dFdC (p < 0.05). Expression levels of the selected proteins in pancreatic cancer tissues of 10 patients with different progression-free survival (PFS) (49-955 days) were quantified, and their relationship with PFS was examined. Only the protein expression level of dCK was significantly correlated with PFS (p < 0.05). Multiple regression analysis was also performed, and combinations of ENT1, UMP-CMP kinase, CTPS1, and dCK were highly correlated with PFS. Our results indicate that the protein expression level of dCK in pancreatic cancer tissue is a good predictor of PFS, and thus dCK may be the best biomarker of dFdC sensitivity in pancreatic cancer patients treated with dFdC, although other proteins would also contribute to dFdC-sensitivity at the cellular level in vivo and in vitro. PMID:26280109

  10. Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

    PubMed Central

    2012-01-01

    Background Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025). Conclusions Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC. PMID:23043286

  11. Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer

    PubMed Central

    Furlong, Fiona; Fitzpatrick, Patricia; O'Toole, Sharon; Phelan, Sine; McGrogan, Barbara; Maguire, Aoife; O'Grady, Anthony; Gallagher, Michael; Prencipe, Maria; McGoldrick, Aloysius; McGettigan, Paul; Brennan, Donal; Sheils, Orla; Martin, Cara; W Kay, Elaine; O'Leary, John; McCann, Amanda

    2012-01-01

    Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3′ UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3′-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3′ UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

  12. Increased 1-year survival and discharge to independent living in overweight hip fracture patients.

    PubMed

    Flodin, Lena; Laurin, Agnes; Lökk, Johan; Cederholm, Tommy; Hedström, Margareta

    2016-04-01

    Background and purpose - Hip fracture patients usually have low body mass index (BMI), and suffer further postoperative catabolism. How BMI relates to outcome in relatively healthy hip fracture patients is not well investigated. We investigated the association between BMI, survival, and independent living 1 year postoperatively. Patients and methods - This prospective multicenter study involved 843 patients with a hip fracture (mean age 82 (SD 7) years, 73% women), without severe cognitive impairment and living independently before admission. We investigated the relationship between BMI and both 1-year mortality and ability to return to independent living. Results - Patients with BMI > 26 had a lower mortality rate than those with BMI < 22 and those with BMI 22-26 (6%, 16%, and 18% respectively; p = 0.006). The odds ratio (OR) for 1-year survival in the group with BMI > 26 was 2.6 (95% CI: 1.2-5.5) after adjustment for age, sex, and physical status. Patients with BMI > 26 were also more likely to return to independent living after the hip fracture (OR = 2.6, 95% CI: 1.4-5.0). Patients with BMI < 22 had similar mortality and a similar likelihood of independent living to those with BMI 22-26. Interpretation - In this selected group of patients with hip fracture, the overweight and obese patients (BMI > 26) had a higher survival rate at 1 year, and returned to independent living to a higher degree than those of normal (healthy) weight. The obesity paradox and the recommendations for optimal BMI need further consideration in patients with hip fracture. PMID:26986549

  13. Increased 1-year survival and discharge to independent living in overweight hip fracture patients

    PubMed Central

    Flodin, Lena; Laurin, Agnes; Lökk, Johan; Cederholm, Tommy; Hedström, Margareta

    2016-01-01

    Background and purpose — Hip fracture patients usually have low body mass index (BMI), and suffer further postoperative catabolism. How BMI relates to outcome in relatively healthy hip fracture patients is not well investigated. We investigated the association between BMI, survival, and independent living 1 year postoperatively. Patients and methods — This prospective multicenter study involved 843 patients with a hip fracture (mean age 82 (SD 7) years, 73% women), without severe cognitive impairment and living independently before admission. We investigated the relationship between BMI and both 1-year mortality and ability to return to independent living. Results — Patients with BMI > 26 had a lower mortality rate than those with BMI < 22 and those with BMI 22–26 (6%, 16%, and 18% respectively; p = 0.006). The odds ratio (OR) for 1-year survival in the group with BMI > 26 was 2.6 (95% CI: 1.2–5.5) after adjustment for age, sex, and physical status. Patients with BMI > 26 were also more likely to return to independent living after the hip fracture (OR = 2.6, 95% CI: 1.4–5.0). Patients with BMI < 22 had similar mortality and a similar likelihood of independent living to those with BMI 22–26. Interpretation — In this selected group of patients with hip fracture, the overweight and obese patients (BMI > 26) had a higher survival rate at 1 year, and returned to independent living to a higher degree than those of normal (healthy) weight. The obesity paradox and the recommendations for optimal BMI need further consideration in patients with hip fracture. PMID:26986549

  14. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Komaki, Ritsuko; Allen, Pamela K.; Wei, Xiong; Blumenschein, George R.; Tang, Ximing; Lee, J. Jack; Welsh, James W.; Wistuba, Ignacio I.; Liu, Diane D.; Hong, Waun Ki

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant

  15. Correlations of survival with progression-free survival, response rate, and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy

    PubMed Central

    Moriwaki, Toshikazu; Yamamoto, Yoshiyuki; Gosho, Masahiko; Kobayashi, Mariko; Sugaya, Akinori; Yamada, Takeshi; Endo, Shinji; Hyodo, Ichinosuke

    2016-01-01

    Background: The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS). Methods: We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated. Results: Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r2=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r2-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents. Conclusions: The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development. PMID:27031848

  16. Tumor Response and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Extensive-Stage Small Cell Lung Cancer (ES-SCLC): Findings Based on North Central Cancer Treatment Group (NCCTG) Trials

    PubMed Central

    Foster, Nathan R.; Qi, Yingwei; Shi, Qian; Krook, James E.; Kugler, John W.; Jett, James R.; Molina, Julian R.; Schild, Steven E.; Adjei, Alex A.; Mandrekar, Sumithra J.

    2010-01-01

    Purpose We investigated the putative surrogate endpoints (PSEs) of best response (BR), complete response (CR), confirmed response (CoR), and progression-free survival (PFS) for associations with Overall Survival (OS), and as possible surrogate endpoints for OS. Methods Individual patient (pt) data from 870 untreated ES-SCLC pts participating in 6 single-arm (274 pts) and 3 randomized trials (596 pts) were pooled. Patient-level associations between PSEs and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of PSEs assessed by the association of treatment effects on OS and individual PSEs. Trial-level surrogacy measures included: R2 from weighted least squares regression model (WLS R2), Spearman's correlation coefficient, and R2 from bivariate survival model (Copula R2). Results Median OS and PFS were 9.6 (95% CI: 9.1-10.0) and 5.5 (95% CI: 5.2-5.9) months, respectively; BR, CR, and CoR rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (HR=0.42 (95% CI: 0.35-0.51); concordance index=0.63; p<0.01), with 6-month PFS being the strongest (HR=0.41 (95% CI: 0.35-0.49); concordance index=0.66; p<0.01). At the trial-level, PFS showed the highest level of surrogacy for OS (WLS R2=0.79; Copula R2=0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (WLS R2≤0.48). Conclusion PFS was strongly associated with OS at both the patient and trial-level. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase III trials. PMID:20960500

  17. Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses

    PubMed Central

    Blumenthal, Gideon M.; Karuri, Stella W.; Zhang, Hui; Zhang, Lijun; Khozin, Sean; Kazandjian, Dickran; Tang, Shenghui; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2015-01-01

    Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect. PMID:25667291

  18. Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

    PubMed Central

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J.A.; Douillard, Jean-Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

    2015-01-01

    Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. PMID:25385741

  19. Weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer: overall survival and updated progression-free survival results from a phase II study.

    PubMed

    Smyth, L M; Iyengar, N M; Chen, M F; Popper, S M; Patil, S; Wasserheit-Lieblich, C; Argolo, D F; Singh, J C; Chandarlapaty, S; Sugarman, S M; Comen, E A; Drullinsky, P R; Traina, T A; Troso-Sandoval, T; Baselga, J; Norton, L; Hudis, C A; Dang, C T

    2016-07-01

    We previously reported progression-free survival (PFS) results on a phase II trial of weekly paclitaxel, trastuzumab, and pertuzumab in patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer (MBC) treated in the first- and second-line setting. Here, we report results for overall survival (OS) and updated PFS after an additional year of follow-up. Patients with HER2-positive MBC with 0-1 prior treatment were eligible. Treatment consisted of paclitaxel (80 mg/m(2)) weekly, and trastuzumab (loading dose 8 mg/kg → 6 mg/kg) and pertuzumab (loading dose 840 mg → 420 mg) every 3 weeks, all given intravenously. Primary endpoint was 6-month PFS. Secondary endpoints included median PFS, 6-month and median OS. Evaluable patients received at least one full dose of treatment. From January 2011 to December 2013, 69 patients were enrolled: 51 (74 %) and 18 (26 %) treated in first- and second-line metastatic settings, respectively. As of July 1, 2015, the median follow-up was 33 months (range 3-49 months; 67 patients were evaluable for efficacy). The median OS was 44 months (95 % CI 37.5-NR) overall and 44 months (95 % CI 38.3-NR) and 37.5 months (95 % CI 30.3-NR) for patients with 0 and 1 prior metastatic treatment, respectively; 6-month OS was 98 % (95 % CI 90-1). The 6-month PFS was 86 % (95 % CI 75-93) overall and 89 % (95 % CI 76-95) and 78 % (95 % CI 51-91) for patients with 0 and 1 prior therapy, respectively; and median PFS was 21.4 months (95 % CI 14.1-NR) overall and 25.7 months (95 % CI 14.1-NR) and 16.9 months (95 % CI 8.5-NR) for patients with 0-1 prior treatment, respectively. Treatment was well tolerated. Updated analysis demonstrates that weekly paclitaxel, when added to trastuzumab and pertuzumab, is associated with a favorable OS and PFS and offers an alternative to docetaxel-based therapy. http://www.ClinicalTrials.gov NCT0127604. PMID:27306421

  20. Using quality-adjusted progression-free survival as an outcome measure to assess the benefits of cancer drugs in randomized-controlled trials: case of the BOLERO-2 trial.

    PubMed

    Diaby, Vakaramoko; Adunlin, Georges; Ali, Askal Ayalew; Tawk, Rima

    2014-08-01

    The aim of this study is to estimate the quality-adjusted progression-free survival (QAPFS) as an effectiveness measure for the treatment arms of the BOLERO-2 trial. For each treatment arm of the trial, QAPFS was estimated by multiplying the overall health utility weights associated with progression-free survival (PFS) (accounting for utility decrements associated with the adverse events of treatments) by the corresponding mean PFS time. Health utility data were obtained from the literature, while mean PFS times were estimated through a survival analysis of the reconstructed individual patient data of the BOLERO-2 trial. PFS (robust mean, (95 % robust confidence interval)) was 44.73 weeks (41.03; 48.43) for Everolimus + Exemestane and 22.98 weeks (19.88; 26.08) for Placebo + Exemestane. The QAPFS (robust mean, (95 % robust confidence interval)) for the treatment arms of the trial was 30.09 (27.60; 32.58) for Everolimus + Exemestane and 16.27 (14.07; 18.46) for Placebo + Exemestane, respectively. Using QAPFS as an outcome measure provides a complete picture of the benefit induced by the treatment arms of the BOLERO-2 trial. The benefit of Everolimus + Exemestane over Placebo + Exemestane observed in the trial is maintained in this analysis. The approach and estimates obtained as part of our analysis can serve as a basis for cost effectiveness analyses of the treatment arms of the BOLERO-2 trial. PMID:25017612

  1. Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide.

    PubMed

    Redjal, Navid; Reinshagen, Clemens; Le, Andrew; Walcott, Brian P; McDonnell, Erin; Dietrich, Jorg; Nahed, Brian V

    2016-05-01

    Valproic acid (VPA) is an anti-epileptic drug with properties of a histone deacetylase inhibitor (HDACi). HDACi play a key role in epigenetic regulation of gene expression and have been increasingly used as anticancer agents. Recent studies suggest that VPA is associated with improved survival in high-grade gliomas. However, effects on lower grade gliomas have not been examined. This study investigates whether use of VPA correlates with tumor grade, histological progression, progression-free and overall survival (OS) in grade II, III, and IV glioma patients. Data from 359 glioma patients (WHO II-IV) treated with temozolomide plus an antiepileptic drug (VPA or another antiepileptic drug) between January 1997 and June 2013 at the Massachusetts General Hospital was analyzed retrospectively. After confounder adjustment, VPA was associated with a 28 % decrease in hazard of death (p = 0.031) and a 28 % decrease in the hazard of progression or death (p = 0.015) in glioblastoma. Additionally, VPA dose correlated with reduced hazard of death by 7 % (p = 0.002) and reduced hazard of progression or death by 5 % (p < 0.001) with each 100 g increase in total dose. Conversely, in grade II and III gliomas VPA was associated with a 118 % increased risk of tumor progression or death (p = 0.014), and every additional 100 g of VPA raised the hazard of progression or death by 4 %, although not statistically significant (p = 0.064). Moreover, grade II and III glioma patients taking VPA had 2.17 times the risk of histological progression (p = 0.020), although this effect was no longer significant after confounder adjustment. In conclusion, VPA was associated with improved survival in glioblastoma in a dose-dependent manner. However, in grade II and III gliomas, VPA was linked to histological progression and decrease in progression-free survival. Prospective evaluation of VPA treatment for glioma patients is warranted to confirm these findings. PMID:26830093

  2. Rituximab plus a CHOP-like regimen, central nervous system prophylaxis, and contralateral testicular irradiation for localized primary testicular diffuse large B-cell lymphoma lead to prolonged progression-free survival.

    PubMed

    Ichikawa, Kunimoto; Noguchi, Masaaki; Koike, Michiaki; Aritaka, Nanae; Sekiguchi, Yasunobu; Sunami, Yoshitaka; Tsutsui, Miyuki; Hosone, Masaru; Hirano, Takao; Gotoh, Akihiko; Komatsu, Norio

    2014-10-01

    We retrospectively evaluated the clinical features, management, and survival of 12 patients (age 51-84 years) with localized primary testicular diffuse large B-cell lymphoma (PTL). All 12 PTL patients underwent orchiectomy. Seven of the 12 patients were treated with strategy A, which consisted of at least six cycles of rituximab (R) plus a CHOP-like regimen, central nervous system (CNS) prophylaxis involving intrathecal chemotherapy (IT) and/or high-dose intravenous methotrexate, and contralateral scrotal irradiation (cRT). The other five patients were treated with strategy B, which included three regimens: orchiectomy alone, orchiectomy plus cRT and IT, and orchiectomy plus 3-4 cycles of R-CHOP plus cRT with or without IT. The median follow-up period was 48 months (range 19-123 months). The 4-year progression-free survival (PFS) rate for the seven patients treated with strategy A was 85.7 %, whereas that for the five patients treated with strategy B was 20 %. The patients treated with strategy A exhibited a significantly higher 4-year PFS rate than those treated with strategy B (P = 0.017). These results confirmed that the administration of a sufficient number of cycles of an R-containing chemotherapy regimen plus cRT plus CNS prophylaxis should be considered as a treatment for localized PTL. PMID:25085255

  3. GATA3 mRNA expression, but not mutation, associates with longer progression-free survival in ER-positive breast cancer patients treated with first-line tamoxifen for recurrent disease.

    PubMed

    Liu, Jingjing; Prager-van der Smissen, Wendy J C; Look, Maxime P; Sieuwerts, Anieta M; Smid, Marcel; Meijer-van Gelder, Marion E; Foekens, John A; Hollestelle, Antoinette; Martens, John W M

    2016-06-28

    In breast cancer, GATA3 mutations have been associated with a favorable prognosis and the response to neoadjuvant aromatase inhibitor treatment. Therefore, we investigated whether GATA3 mutations predict the outcome of tamoxifen treatment in the advanced setting. In a retrospective study consisting of 235 hormone-naive patients with ER-positive breast cancer who received tamoxifen as first-line treatment for recurrent disease, GATA3 mutations (in 14.0% of patients) did not significantly associate with either the overall response rate (ORR) or with the length of progression-free survival (PFS) after the start of tamoxifen therapy. Interestingly, among 148 patients for whom both mutation and mRNA expression data were available, GATA3 mutations associated with an increased expression of GATA3. However, only 23.7% of GATA3 high tumors had a mutation. Evaluation of the clinical significance of GATA3 mRNA revealed that it was associated with prolonged PFS, but not with the ORR, also in multivariate analysis. Thus, GATA3 mRNA expression, but not GATA3 mutation, is an independent predictor of prolonged PFS in ER-positive breast cancer patients who received first-line tamoxifen for recurrent disease. Besides GATA3 mutation, other mechanisms must exist that underlie increased GATA3 levels. PMID:27018307

  4. Magnitude of the Benefit of Progression-Free Survival as a Potential Surrogate Marker in Phase 3 Trials Assessing Targeted Agents in Molecularly Selected Patients with Advanced Non-Small Cell Lung Cancer: Systematic Review

    PubMed Central

    Hotta, Katsuyuki; Kato, Yuka; Leighl, Natasha; Takigawa, Nagio; Gaafar, Rabab Mohamed; Kayatani, Hiroe; Hirata, Taizo; Ohashi, Kadoaki; Kubo, Toshio; Tabata, Masahiro; Tanimoto, Mitsune; Kiura, Katsuyuki

    2015-01-01

    Background In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC), overall survival (OS) as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed. Methods and Findings We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs) or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an “all-comer” design). Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs) (0.99 vs. 1.04), the former exhibited greater progression-free survival-hazard ratios (PFS-HR) (mean, 0.40 vs. 1.01; P<0.01). A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%). The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01). An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%. Conclusion The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of ∼0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial. PMID:25775395

  5. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

    PubMed

    Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

    2016-01-01

    In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC. PMID:26596971

  6. Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Fang, Wenfeng; Yan, Yue; Hu, Zhihuang; Hong, Shaodong; Wu, Xuan; Qin, Tao; Liang, Wenhua; Zhang, Li

    2014-01-01

    Backgrounds It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered. Methods Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively. Results A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies. Conclusions For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs. PMID:25222496

  7. Interim fluorine-18 fluorodeoxyglucose PET-computed tomography and cell of origin by immunohistochemistry predicts progression-free and overall survival in diffuse large B-cell lymphoma patients in the rituximab era

    PubMed Central

    Hallack Neto, Abrahão; Siqueira, Sheila; Lage, Luis Alberto de Padua Covas; de Paula, Henrique M.; Coutinho, Arthur M.; Pereira, Juliana

    2016-01-01

    Objective The aim of this study was to analyze the prognostic value of the interim PET (iPET)-computed tomography (CT) (iPET-CT) after two cycles of immunochemotherapy with the R-CHOP protocol in patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) treated with a curative intent in combination with the neoplastic cell origin defined by Hans’s immunohistochemstry algorithm followed in a reference center for cancer treatment in Brazil. Materials and methods We prospectively evaluated 147 DLBCL patients treated with R-CHOP-21 to assess the value of the International Prognostic Index, iPET-CT, and cell of origin by immunohistochemistry as prognostic markers in the rituximab era. Fluorine-18 fluorodeoxyglucose PET-CT was performed after two cycles (iPET-CT) and at the end of treatment in 111 patients. Lymphoma cases were categorized into germinal center (GC) and nongerminal center subtypes by immunohistochemistry according to Hans’s algorithm. Results The median age of GC-DLBCL patients (52.7 years) was lower than that of nongerminal center-DLBCL patients (59.4 years) (P=0.021); in addition, it was lower in patients with negative iPET-CT findings (52.7 years) versus positive findings (59.4 years) (P=0.031). The overall survival at 48 months was 100% for iPET-CT-negative GC-DLBCL patients and 61.2% for iPET-CT-positive GC-DLBCL patients (P=0.002). Progression-free survival at 30 months was 100% for iPET-CT-negative GC-DLBCL patients and 60.3% for iPET-CT-positive GC-DLBCL patients (P=0.001). Conclusion We conclude that iPET-CT associated with cell origin identified a very good prognostic group in DLBCL patients treated with R-CHOP. Video Abstract: http://links.lww.com/NMC/A59 PMID:27281359

  8. SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

    SciTech Connect

    Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W; Latifi, K; Hoffe, S; Moros, E; Saeed, Nadia; Tan, S; Shridhar, R

    2015-06-15

    Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

  9. Multi-Trial Evaluation of Progression-Free Survival (PFS) as a Surrogate Endpoint for Overall Survival (OS) in First-Line Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

    PubMed Central

    Foster, Nathan R.; Renfro, Lindsay A.; Schild, Steven E.; Redman, Mary W.; Wang, Xiaofei F.; Dahlberg, Suzanne E.; Ding, Keyue; Bradbury, Penelope A.; Ramalingam, Suresh S.; Gandara, David R.; Shibata, Taro; Saijo, Nagahiro; Vokes, Everett E.; Adjei, Alex A.; Mandrekar, Sumithra J.

    2015-01-01

    Introduction We previously reported that PFS may be a candidate surrogate endpoint for OS in first-line ES-SCLC using data from 3 randomized trials (Foster, Cancer 2011). In this validation study (N0424-Alliance), we assessed the patient- and trial-level surrogacy of PFS using data from 7 new first-line phase II/III ES-SCLC trials and across all 10 trials as well (7 new, 3 previous). Methods Individual patient data were utilized across the 7 new trials (2259 patients) and all 10 trials (2855 patients). Patient-level surrogacy (Kendall’s τ) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed via association of the log hazard ratios on OS and PFS across trials, including weighted (by trial size) least squares regression of Cox model effects (WLS R2) and correlation of the copula effects (Copula R2). The minimum effect on the surrogate (MES) needed to detect a non-zero treatment effect on OS was also calculated. Results The median OS and PFS across all 10 trials were 9.8 and 5.9 months, respectively. PFS showed strong surrogacy within the 7 new trials (Copula R2 = 0.90 (SE=0.27); WLS R2 = 0.83 (95% CI: 0.43, 0.95); MES=0.67; Kendall’s τ = 0.58) and across all 10 trials (Copula R2 =0.81 (SE=0.25); WLS R2=0.77 (95% CI: 0.47–0.91); MES=0.70; Kendall’s τ =0.57). Conclusions PFS demonstrated strong surrogacy for OS in first-line ES-SCLC based on this external validation study of individual patient data. PFS is a good alternative endpoint to OS and should be considered when resource constraints (time or patient) might make it useful or desirable in place of OS. Additional analyses are needed to assess its appropriateness for targeted agents in this disease setting. PMID:26134227

  10. Hospitalization for Pneumonia is Associated With Decreased 1-Year Survival in Patients With Type 2 Diabetes: Results From a Prospective Cohort Study.

    PubMed

    Falcone, Marco; Tiseo, Giusy; Russo, Alessandro; Giordo, Laura; Manzini, Elisa; Bertazzoni, Giuliano; Palange, Paolo; Taliani, Gloria; Cangemi, Roberto; Farcomeni, Alessio; Vullo, Vincenzo; Violi, Francesco; Venditti, Mario

    2016-02-01

    Diabetes mellitus is a frequent comorbid conditions among patients with pneumonia living in the community.The aim of our study is to evaluate the impact of hospitalization for pneumonia on early (30 day) and late mortality (1 year) in patients with type 2 diabetes mellitus.Prospective comparative cohort study of 203 patients with type 2 diabetes hospitalized for pneumonia versus 206 patients with diabetes hospitalized for other noninfectious causes from January 2012 to December 2013 at Policlinico Umberto I (Rome). Enrolled patients were followed up to discharge and up to 1 year after initial hospital admission or death.Overall, 203 patients with type 2 diabetes admitted to hospital for pneumonia were compared to 206 patients with type 2 diabetes admitted for other causes (39.3% decompensated diabetes, 21.4% cerebrovascular diseases, 9.2% renal failure, 8.3% acute myocardial infarction, and 21.8% other causes). Compared to control patients, those admitted for pneumonia showed a higher 30-day (10.8% vs 1%, P < 0.001) and 1-year mortality rate (30.3% vs 16.8%, P < 0.001). Compared to survivors, nonsurvivor patients with pneumonia had a higher incidence of moderate to severe chronic kidney disease, hemodialysis, and malnutrition were more likely to present with a mental status deterioration, and had a higher number of cardiovascular events during the follow-up period. Cox regression analysis found age, Charlson comorbidity index, pH < 7.35 at admission, hemodialysis, and hospitalization for pneumonia as variables independently associated with mortality.Hospitalization for pneumonia is associated with decreased 1-year survival in patients with type 2 diabetes, and appears to be a major determinant of long-term outcome in these patients. PMID:26844461

  11. Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non-Small-Cell Lung Cancer

    SciTech Connect

    Werner-Wasik, Maria Swann, R. Suzanne; Bradley, Jeffrey; Graham, Mary; Emami, Bahman; Purdy, James; Sause, William

    2008-02-01

    Purpose: Patients with non-small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels. We investigated the effect of the gross tumor volume (GTV) on the outcome. Methods and Materials: The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller ({<=}45 cm{sup 3}) vs. larger (>45 cm{sup 3}) tumors. Results: The distribution of the GTV was as follows: {<=}45 cm{sup 3} in 79 (49%) and >45 cm{sup 3} in 82 (51%) of 161 patients. The median GTV was 47.3 cm{sup 3}. N0 status and female gender were associated with better tumor responses. Patients with smaller ({<=}45 cm{sup 3}) tumors achieved a longer MST and better PFS than did patients with larger (>45 cm{sup 3}) tumors (29.7 vs. 13.3 months, p < 0.0001; and 15.8 vs. 8.3 months, p < 0.0001, respectively). Increasing the radiation dose had no effect on the MST or PFS. On multivariate analysis, only a smaller GTV was a significant prognostic factor for improved MST and PFS (hazard ratio [HR], 2.12, p = 0.0002; and HR, 2.0, p = 0.0002, respectively). The GTV as a continuous variable was also significantly associated with the MST and PFS (HR, 1.59, p < 0.0001; and HR, 1.39, p < 0.0001, respectively). Conclusions: Radiation dose escalation up to 90.3 Gy did not result in improved MST or PFS. The tumor responses were greater in node-negative patients and women. An increasing GTV was strongly associated with decreased MST and PFS. Future radiotherapy trials patients might need to use stratification by tumor volume.

  12. The LMCE5 unselected cohort of 25 children consecutively diagnosed with untreated stage 4 neuroblastoma over 1 year at diagnosis

    PubMed Central

    Frappaz, D; Perol, D; Michon, J; Berger, C; Coze, C; Bernard, J L; Zucker, J M; Philip, T

    2002-01-01

    The Lyon-Marseille-Curie-Est (LMCE) of France cooperative group has previously reported successive series of unselected stage four children older than 1 year at diagnosis with metastatic neuroblastoma (LMCE 1 and 3). The goal of LMCE 5 study was to increase progression free survival rate as compared to LMCE 1 and 3. Based on improvements reported with post induction chemotherapy, the LMCE 5 used post induction for all children, but omitted total body irradiation and immunomagnetic purging in megatherapy regimen for all children. Twenty-five sequentially diagnosed children received an induction regimen which compared with previous induction included an increased dose of etoposide and cyclophosphamide, delivered similar dose of cisplatinum, and deleted doxorubicin and vincristin. After surgery treatment was stratified based on response and eligible children received etoposide carboplatin (LMCE 5A : n=10)±doxorubicin (LMCE 5B–C n=13) followed by megatherapy (melphalan without total body irradiation and unpurged peripheral blood stem cell rescue). The increase in drug doses during induction did not improve remission rate. The progression free survival at 6 years is 8%. It is significantly worse than LMCE 3, and equivalent to LMCE 1 study though toxic death rate has decreased with increasing experience. Failure to improve the response rate during induction and reducing the megatherapy regimen may be the main factors in this disappointing result. Modified strategies for induction, non toxic alternative to total body irradiation, and post megatherapy regimen should be developed. British Journal of Cancer (2002) 87, 1197–1203. doi:10.1038/sj.bjc.6600627 www.bjcancer.com © 2002 Cancer Research UK PMID:12439705

  13. Emotional Development: 1 Year Olds

    MedlinePlus

    ... Español Text Size Email Print Share Emotional Development: 1 Year Olds Page Content Article Body Throughout her ... for shelter. She may seem to change from one moment to the next, or she may seem ...

  14. Social Development: 1 Year Olds

    MedlinePlus

    ... Stages Prenatal Baby Toddler Fitness Nutrition Toilet Training Preschool Gradeschool Teen Young Adult Healthy Children > Ages & Stages > Toddler > Social Development: 1 Year Olds Ages & Stages Listen Español ...

  15. Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction

    PubMed Central

    Rawstron, Andy C.; Gregory, Walter M.; de Tute, Ruth M.; Davies, Faith E.; Bell, Sue E.; Drayson, Mark T.; Cook, Gordon; Jackson, Graham H.; Morgan, Gareth J.; Child, J. Anthony

    2015-01-01

    The detection of minimal residual disease (MRD) in myeloma using a 0.01% threshold (10−4) after treatment is an independent predictor of progression-free survival (PFS), but not always of overall survival (OS). However, MRD level is a continuous variable, and the predictive value of the depth of tumor depletion was evaluated in 397 patients treated intensively in the Medical Research Council Myeloma IX study. There was a significant improvement in OS for each log depletion in MRD level (median OS was 1 year for ≥10%, 4 years for 1% to <10%, 5.9 years for 0.1% to <1%, 6.8 years for 0.01% to <0.1%, and more than 7.5 years for <0.01% MRD). MRD level as a continuous variable determined by flow cytometry independently predicts both PFS and OS, with approximately 1 year median OS benefit per log depletion. The trial was registered at www.isrctn.com as #68454111. PMID:25645353

  16. Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy

    SciTech Connect

    Merrick, Gregory S. . E-mail: gmerrick@wheelinghospital.com; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A. M.S.; Adamovich, Edward

    2006-07-01

    Purpose: To determine if androgen-deprivation therapy (ADT) has an impact on cause-specific, biochemical progression-free, or overall survival after prostate brachytherapy. Methods and Materials: From April 1995 through June 2002, 938 consecutive patients underwent brachytherapy for clinical Stage T1b to T3a (2002 AJCC) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. A total of 382 patients (40.7%) received ADT with a duration of 6 months or less in 277 and more than 6 months in 105. The median follow-up was 5.4 years. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific, biochemical progression-free, and overall survival rates for the entire cohort were 96.4%, 95.9%, and 78.1%, respectively. Except for biochemical progression-free survival in high-risk patients, ADT did not statistically impact any of the three survival categories. A Cox linear-regression analysis demonstrated that Gleason score was the best predictor of cause-specific survival, whereas percent-positive biopsies, prostate volume, and risk group predicted for biochemical progression-free survival. Patient age and tobacco use were the strongest predictors of overall survival. One hundred two patients have died, with 80 of the deaths a result of cardiovascular disease (54) and second malignancies (26). To date, only 12 patients have died of metastatic prostate cancer. Conclusions: After brachytherapy, androgen-deprivation therapy did not have an impact on cause-specific or overall survival for any risk group; however, ADT had a beneficial effect on biochemical progression-free survival in high-risk patients. Cardiovascular disease and second malignancies far outweighed prostate cancer as competing causes of death.

  17. Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment

    PubMed Central

    Yang, Wei; Yan, Kun; Goldberg, S Nahum; Ahmed, Muneeb; Lee, Jung-Chieh; Wu, Wei; Zhang, Zhong-Yi; Wang, Song; Chen, Min-Hua

    2016-01-01

    AIM: To investigate the long-term survival and prognostic factors in hepatocellular carcinoma (HCC) patients undergoing radiofrequency ablation (RFA) as a first-line treatment. METHODS: From 2000 to 2013, 316 consecutive patients with 404 HCC (1.0-5.0 cm; mean: 3.2 ± 1.1 cm) underwent ultrasonography-guided percutaneous RFA as a first-line treatment. There were 250 males and 66 females with an average age of 60.1 ± 10.8 years (24-87 years). Patients were followed for 1 year to > 10 years after RFA (234, 181, 136, and 71 for 3, 5, 7, and 10 years, respectively). Overall local response rates and long-term survival rates were assessed. Survival results were generated using Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression model. RESULTS: In total, 548 RFA sessions were performed and major complications occurred in 10 sessions (1.8%). Local tumor progression and/or new tumor development were observed in 43.3% (132/305) of the patients during the follow-up period. Overall 5- and 10-year survival rates were 49.7% and 28.4%, respectively. Based on multivariate analysis, three factors were identified as independent prognostic factors for overall survival: Child-Pugh classification (HR = 4.054, P < 0.001), portal vein hypertension (HR = 2.743, P = 0.002), and tumor number (HR = 2.693, P = 0.003). The local progression-free 5- and 10-year survival rates were 42.7% and 19.5%. In addition to the Child-Pugh classification and the number of tumors, the number of RFA sessions (HR = 1.550, P = 0.002) was associated with local progression-free survival. CONCLUSION: RFA can achieve acceptable outcomes for HCC patients as a first-line treatment, especially for patients with Child-Pugh class A, patients with a single tumor and patients without portal vein hypertension. PMID:26973395

  18. Choking - unconscious adult or child over 1 year

    MedlinePlus

    Choking - unconscious adult or child over 1 year; First aid - choking - unconscious adult or child over 1 year; ... or the local emergency number while you begin first aid and CPR. If you are alone, shout for ...

  19. Choking - unconscious adult or child over 1 year

    MedlinePlus

    ... choking - unconscious adult or child over 1 year; CPR - choking - unconscious adult or child over 1 year ... emergency number while you begin first aid and CPR. If you are alone, shout for help and ...

  20. MGMT Promoter Methylation Correlates with an Overall Survival Benefit in Chinese High-Grade Glioblastoma Patients Treated with Radiotherapy and Alkylating Agent-Based Chemotherapy: A Single-Institution Study

    PubMed Central

    Shen, Dong; Liu, Tao; Lin, Qingfen; Lu, Xiangdong; Wang, Qiong; Lin, Feng; Mao, Weidong

    2014-01-01

    Promoter methylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene has been considered a prognostic marker and has become more important in the treatment of glioblastoma. However, reports on the correlation between MGMT and clinical outcomes in Chinese glioblastoma patients are very scarce. In this study, quantitative methylation data were obtained by the pyrosequencing of tumor tissues from 128 GBM patients. The median overall survival (OS) was 13.1 months, with a 1-year survival of 45.3%. The pyrosequencing data were reproducible based on archived samples yielding data for all glioblastomas. MGMT promoter methylation was detected in 75/128 cases (58.6%), whereas 53/128 (41.4%) cases were unmethylated. Further survival analysis also revealed that methylation was an independent prognostic factor associated with prolonged OS but not with progression-free survival (PFS) (p = 0.029 and p = 0.112, respectively); the hazard radios were 0.63 (95% CI: 0.42–0.96) and 0.72 (95% CI: 0.48–1.09), respectively. These data indicated that MGMT methylation has prognostic significance in patients with newly diagnosed high-grade glioblastoma undergoing alkylating agent-based chemotherapy after surgical resection. PMID:25211033

  1. Spiritual absence and 1-year mortality after hematopoietic stem cell transplant.

    PubMed

    Pereira, Deidre B; Christian, Lisa M; Patidar, Seema; Bishop, Michelle M; Dodd, Stacy M; Athanason, Rebecca; Wingard, John R; Reddy, Vijay S

    2010-08-01

    Religiosity and spirituality have been associated with better survival in large epidemiologic studies. This study examined the relationship between spiritual absence and 1-year all-cause mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Depression and problematic compliance were examined as possible mediators of a significant spiritual absence-mortality relationship. Eighty-five adults (mean = 46.85 years old, SD = 11.90 years) undergoing evaluation for allogeneic HSCT had routine psychologie evaluation prior to HSCT admission. The Millon Behavioral Medicine Diagnostic was used to assess spiritual absence, depression, and problematic compliance, the psychosocial predictors of interest. Patient status at 1 year and survival time in days were abstracted from medical records. Cox regression analysis was used to examine the relationship between the psychosocial factors of interest and mortality after adjusting for relevant biobehavioral factors. Twenty-nine percent (n = 25) of participants died within 1 year of HSCT. After covarying for disease type, individuals with the highest spiritual absence and problematic compliance scores were significantly more likely to die 1-year post-HSCT (hazard ratio [HR] = 2.49, P = .043 and HR = 3.74, P = .029, respectively), particularly secondary to infection, sepsis, or graft-versus-host disease (GVHD) (HR = 4.56, P = .01 and HR = 5.61, P = .014), relative to those without elevations on these scales. Depression was not associated with 1-year mortality, and problematic compliance did not mediate the relationship between spiritual absence and mortality. These preliminary results suggest that both spiritual absence and problematic compliance may be associated with poorer survival following HSCT. Future research should examine these relations in a larger sample using a more comprehensive assessment of spirituality. PMID:20227510

  2. Survival outcome according to KRAS mutation status in newly diagnosed patients with stage IV non-small cell lung cancer treated with platinum doublet chemotherapy

    PubMed Central

    Brady, Anna K.; McNeill, Jonathan D.; Judy, Brendan; Bauml, Joshua; Evans, Tracey L.; Cohen, Roger B.; Langer, Corey; Vachani, Anil; Aggarwal, Charu

    2015-01-01

    Introduction Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20–25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear. Methods We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods. Results All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58–2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48–1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01). Conclusions KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy. PMID:26471290

  3. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts.

    PubMed

    Loupy, Alexandre; Vernerey, Dewi; Tinel, Claire; Aubert, Olivier; Duong van Huyen, Jean-Paul; Rabant, Marion; Verine, Jérôme; Nochy, Dominique; Empana, Jean-Philippe; Martinez, Frank; Glotz, Denis; Jouven, Xavier; Legendre, Christophe; Lefaucheur, Carmen

    2015-07-01

    Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000-2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P<0.001). In a multivariate Cox model, subclinical ABMR at 1 year was independently associated with a 3.5-fold increase in graft loss (95% confidence interval, 2.1 to 5.7) along with eGFR and proteinuria (P<0.001). Subclinical ABMR was associated with more rapid progression to transplant glomerulopathy. Of patients with subclinical TCMR at 1 year, only those who further developed de novo donor-specific antibodies and transplant glomerulopathy showed higher risk of graft loss compared with patients without rejection. Our findings suggest that subclinical TCMR and subclinical ABMR have distinct effects on long-term graft loss. Subclinical ABMR detected at the 1-year screening biopsy carries a prognostic value independent of initial donor-specific antibody status, previous immunologic events, current eGFR, and proteinuria. PMID:25556173

  4. Choking first aid - adult or child over 1 year - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100222.htm Choking first aid - adult or child over 1 year - series—Part ... occur in as little as 4 minutes. Rapid first aid for choking can save a life. The universal ...

  5. Choking first aid - infant under 1 year - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100221.htm Choking first aid - infant under 1 year - series—Part 1 To ... Loss of consciousness if blockage is not cleared FIRST AID 1. DO NOT perform these steps if the ...

  6. Results with SynCardia total artificial heart beyond 1 year.

    PubMed

    Torregrossa, Gianluca; Morshuis, Michiel; Varghese, Robin; Hosseinian, Leila; Vida, Vladimiro; Tarzia, Vincenzo; Loforte, Antonio; Duveau, Daniel; Arabia, Francisco; Leprince, Pascal; Kasirajan, Vigneshwa; Beyersdorf, Friedhelm; Musumeci, Francesco; Hetzer, Roland; Krabatsch, Thoamas; Gummert, Jan; Copeland, Jack; Gerosa, Gino

    2014-01-01

    Mechanical circulatory support devices have been increasingly used for long-term support. We reviewed outcomes in all patients supported with a SynCardia total artificial heart (TAH) for more than 1 year to assess its safety in long-term support. As of December 2011, all 47 patients who received the TAH from 10 centers worldwide were included in this retrospective study. Clinical data were collected on survival, infections, thromboembolic and hemorrhagic events, device failures, and antithrombotic therapy. The mean age of patients was 50 ± 1.57 years, the median support time was 554 days (range 365-1373 days). The primary diagnosis was dilated cardiomiopathy in 23 patients, ischemic in 15, and "other" in 9. After a minimum of 1 year of support, 34 patients (72%) were successfully transplanted, 12 patients (24%) died while on device support, and 1 patient (2%) is still supported. Five patients (10%) had a device failure reported. Major complications were as follows: systemic infections in 25 patients (53%), driveline infections in 13 patients (27%), thromboembolic events in 9 patients (19%), and hemorrhagic events in 7 patients (14%). SynCardia TAH has proven to be a reliable and effective device in replacing the entire heart. In patients who reached a minimum of 1 year of support, device failure rate is acceptable and only in two cases was the leading cause of death. Infections and hemorrhagic events were the major causes of death. Patients who remain supported beyond 1 year are still likely to survive to transplantation. PMID:25158888

  7. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Noerskov, K H; Schjødt, I; Syrjala, K L; Jarden, M

    2016-06-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction 1 year after treatment; and (2) associations between sexual dysfunction, body image, anxiety and depression. This controlled prospective cohort study was conducted from October 2010 to November 2013. Patients completed assessments 2-3 weeks before HSCT (N=124) and 1 year after treatment (N=63). Assessment included descriptive data, Sexual Functioning Questionnaire, Body Image Scale and Hospital Anxiety and Depression Scale. The results showed a significant decline in overall sexual function in both men and women (P=<0.001, P=0.010, respectively), although men generally scored higher than women. Forty-seven percent of men and 60% of women reported at least one physical sexual problem 1 year after HSCT. Patients with chronic GVHD trended toward reporting lower levels of sexual function. Finally, women with chronic GVHD scored lower than those without chronic GVHD on the sexual function problem subscale (P=0.008). Sexual dysfunction remains a major problem for men and women 1 year after HSCT and requires routine evaluation and treatment after HSCT. PMID:26878660

  8. Anxiety Sensitivity and Panic Attacks: A 1-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Li, Wen; Zinbarg, Richard E.

    2007-01-01

    The hypothesis that anxiety sensitivity (AS) is a risk factor for panic genesis has obtained compelling support, but the clinical/practical importance of AS in panic genesis has been questioned. In addition, the association between panic experience and AS increase has not been clearly demonstrated. Through this 1-year longitudinal study among…

  9. The clinical outcome of scaphoid fracture malunion at 1 year.

    PubMed

    Forward, D P; Singh, H P; Dawson, S; Davis, T R C

    2009-02-01

    The aim of this study was to assess the effect of malunion of scaphoid fractures on the clinical outcome at 1 year. Forty-two consecutive patients with united scaphoid waist fractures which had been treated non-operatively underwent longitudinal CT scans to confirm union and assess malunion at 12 to 18 weeks after injury. A blind clinical assessment was made and the Patient Evaluation Measure (PEM) and DASH questionnaires were completed by all the patients 1 year after injury. The group consisted of 38 men and four women with a mean age of 31 years at the time of injury. Correlation analysis revealed no significant relationships between any of the outcome measures (range of motion, grip strength and PEM and DASH scores) and any of the three measures of malunion (height-to-length ratio, the dorsal cortical angle and the lateral intra-scaphoid angle). PMID:19129358

  10. Secondary preventive medication persistence and adherence 1 year after stroke

    PubMed Central

    Olson, D.M.; Zhao, X.; Pan, W.; Zimmer, L.O.; Goldstein, L.B.; Alberts, M.J.; Fagan, S.C.; Fonarow, G.C.; Johnston, S.C.; Kidwell, C.; LaBresh, K.A.; Ovbiagele, B.; Schwamm, L.; Peterson, E.D.

    2011-01-01

    Objective: Data on long-term use of secondary prevention medications following stroke are limited. The Adherence eValuation After Ischemic stroke–Longitudinal (AVAIL) Registry assessed patient, provider, and system-level factors influencing continuation of prevention medications for 1 year following stroke hospitalization discharge. Methods: Patients with ischemic stroke or TIA discharged from 106 hospitals participating in the American Heart Association Get With The Guidelines–Stroke program were surveyed to determine their use of warfarin, antiplatelet, antihypertensive, lipid-lowering, and diabetes medications from discharge to 12 months. Reasons for stopping medications were ascertained. Persistence was defined as continuation of all secondary preventive medications prescribed at hospital discharge, and adherence as continuation of prescribed medications except those stopped according to health care provider instructions. Results: Of the 2,880 patients enrolled in AVAIL, 88.4% (2,457 patients) completed 1-year interviews. Of these, 65.9% were regimen persistent and 86.6% were regimen adherent. Independent predictors of 1-year medication persistence included fewer medications prescribed at discharge, having an adequate income, having an appointment with a primary care provider, and greater understanding of why medications were prescribed and their side effects. Independent predictors of adherence were similar to those for persistence. Conclusions: Although up to one-third of stroke patients discontinued one or more secondary prevention medications within 1 year of hospital discharge, self-discontinuation of these medications is uncommon. Several potentially modifiable patient, provider, and system-level factors associated with persistence and adherence may be targets for future interventions. PMID:21900638

  11. Intracranial idiopathic hypertension: 1-year follow-up study.

    PubMed

    D'Amico, D; Curone, M; Erbetta, A; Farago', G; Bianchi-Marzoli, S; Ciasca, P; Bussone, G; Chiapparini, L

    2014-05-01

    Standard guidelines for ongoing management, as well as definitive data about the long-term course of idiopathic intracranial hypertension (IIH) are not available. The aim of this study was to compare several clinical and instrumental variables as assessed at the time of diagnosis and then after 1 year in a sample of IIH patients. A total of 21 patients were studied. Our results confirmed that headache and TVO are the most frequent symptoms in IIH patients, and that overweight is a very common feature. A trend towards a favorable outcome in patients followed for 1 year and treated by usual medical therapy was found: intracranial pressure was lower at follow-up; improvement of headache and transient visual obscurations, as well as of papilledema, was reported in most patients. On the other hand, neuroradiological findings (such as empty sella, perioptic subarachnoid space distension, narrowing of the transverse sinuses) were substantially stable at follow. These findings may be relevant for future research as far as understanding the role of different clinical and instrumental findings as diagnostic items as well as predictors of outcome in IIH. PMID:24867861

  12. TERT promoter mutations in melanoma survival.

    PubMed

    Nagore, Eduardo; Heidenreich, Barbara; Rachakonda, Sívaramakrishna; Garcia-Casado, Zaida; Requena, Celia; Soriano, Virtudes; Frank, Christoph; Traves, Victor; Quecedo, Esther; Sanjuan-Gimenez, Josefa; Hemminki, Kari; Landi, Maria Teresa; Kumar, Rajiv

    2016-07-01

    Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. PMID:26875008

  13. Otitis media with effusion in children younger than 1 year

    PubMed Central

    Di Francesco, Renata Cantisani; Barros, Vivian Boschesi; Ramos, Rafael

    2016-01-01

    Abstract Objective: To determine the prevalence of otitis media with effusion in children younger than 1 year and its association with the season of the year, artificial feeding, environmental and perinatal factors. Methods: Retrospective study of 184 randomly included medical records from a total of 982 healthy infants evaluated for hearing screening tests. Diagnosis of otitis media with effusion was based on otoscopy (amber-gold color, fluid level, handle of malleus position), type B tympanometric curves and absence of otoacoustic emissions. Incomplete medical records or those describing acute otitis media, upper respiratory tract infections on the assessment day or in the last 3 months, neuropathies and craniofacial anomalies were excluded. Data such as gestational age, birth weight, Apgar score, type of feeding and day care attendance were compared between children with and without otitis media with effusion through likelihood tests and multivariate analysis. Results: 25.3% of 184 infants had otitis media with bilateral effusion; 9.2% had unilateral. In infants with otitis media, the following were observed: chronological age of 9.6±1.7 months; gestational age >38 weeks in 43.4% and birth weight >2500g in 48.4%. Otitis media with effusion was associated with winter/fall, artificial feeding, Apgar score <7 and day care attendance. The multivariate analysis showed that artificial feeding is the factor most often associated to otitis media with effusion. Conclusions: Otitis media with effusion was found in about one third of children younger than 1 year and was mainly associated with artificial feeding. PMID:26559603

  14. High levels of genomic aberrations in serous ovarian cancers are associated with better survival.

    PubMed

    Baumbusch, Lars O; Helland, Åslaug; Wang, Yun; Liestøl, Knut; Schaner, Marci E; Holm, Ruth; Etemadmoghadam, Dariush; Alsop, Kathryn; Brown, Pat; Mitchell, Gillian; Fereday, Sian; DeFazio, Anna; Bowtell, David D L; Kristensen, Gunnar B; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise

    2013-01-01

    Genomic instability and copy number alterations in cancer are generally associated with poor prognosis; however, recent studies have suggested that extreme levels of genomic aberrations may be beneficial for the survival outcome for patients with specific tumour types. We investigated the extent of genomic instability in predominantly high-grade serous ovarian cancers (SOC) using two independent datasets, generated in Norway (n = 74) and Australia (n = 70), respectively. Genomic instability was quantified by the Total Aberration Index (TAI), a measure of the abundance and genomic size of copy number changes in a tumour. In the Norwegian cohort, patients with TAI above the median revealed significantly prolonged overall survival (p<0.001) and progression-free survival (p<0.05). In the Australian cohort, patients with above median TAI showed prolonged overall survival (p<0.05) and moderately, but not significantly, prolonged progression-free survival. Results were confirmed by univariate and multivariate Cox regression analyses with TAI as a continuous variable. Our results provide further evidence supporting an association between high level of genomic instability and prolonged survival of high-grade SOC patients, possibly as disturbed genome integrity may lead to increased sensitivity to chemotherapeutic agents. PMID:23372714

  15. Surviving Cancer

    MedlinePlus

    ... Watch the video to learn more about these breast cancer survivors. To enlarge the video, click the brackets in the lower right-hand corner. To reduce the video, press the Escape (Esc) button on your keyboard.) Age and Health May Affect Survival A person's age, and more importantly his or ...

  16. Beyond Survival

    ERIC Educational Resources Information Center

    Steffenson, Dave

    1975-01-01

    The author argues that environmentalists need to realize that the present ecological crisis is essentially a value crisis, not merely a fight for survival alone. He envisions a complete value change for the human population and advocates the incorporation of value strategies into all environmental education programs immediately. (MA)

  17. Infectious complications more than 1 year after liver transplantation: a 3-decade nationwide experience.

    PubMed

    Aberg, F; Mäkisalo, H; Höckerstedt, K; Isoniemi, H

    2011-02-01

    Because few reports have addressed infections late (≥1 year) after liver transplantation (LT), we evaluated the incidence, risk factors and pathogens involved. Infection data were from the Finnish LT registry, with starting date, type and relevant pathogens for 501 Finnish adult LT patients surviving1 year post-transplant. Follow-up end points were end of study, death or retransplantation. Logistic regression to assess risk factors was adjusted for age, gender and follow-up time. With 3923 person-years of follow-up, overall infection incidence was 66/1000 person-years; 155 (31%) suffered 259 infections, and two-thirds experienced only one infection. Cholangitis (20%), pneumonia (19%) and sepsis (14%) were most common. The most frequent bacteria were Enterococcus spp. and Escherichia coli, and the most frequent viruses cytomegalovirus and varicella zoster virus. Fungal infections were rare (n = 7). With 13 fatal infections, 17% of all late deaths involved infection. Primary sclerosing cholangitis (PSC) and Roux-en-Y-type biliary anastomosis were associated with cholangitis; 18% of PSC patients suffered late cholangitis. Late acute rejection was associated with sepsis. Age, gender or cytomegalovirus did not significantly influence late infections. In conclusion, although infection risk under maintenance immunosuppression therapy is relatively low, particular vigilance regarding cholangitis, pneumonia and sepsis seems appropriate. PMID:21219571

  18. Immediate Implant Placement in a Patient With Osteoporosis Undergoing Bisphosphonate Therapy: 1-Year Preliminary Prospective Study.

    PubMed

    Siebert, Tomas; Jurkovic, Richard; Statelova, Dagmar; Strecha, Juraj

    2015-07-01

    The purposes of this preliminary study are to assess the risk of developing bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a patient with osteoporosis using zoledronic acid and to report the results of a 1-year prospective clinical study regarding 5 immediately inserted implants in the anterior mandible. For this comparative prospective study, 24 female patients, aged ≥54 years, were chosen, all with partially edentulous mandibles. Group A consisted of 12 patients with osteoporosis taking zoledronic acid receiving a once-yearly intravenous infusion of zoledronic acid (5 mg). Control group B consisted of 12 other patients without osteoporosis and not taking drugs. In both groups, the remaining teeth were extracted before 120 implants, 3.7-mm wide and 16-mm long, were immediately installed in the interforaminal region of the mandibles. The 1-year implant survival rate was 100%. No apparent necrotic bone was observed among patients receiving zoledronic acid (group A) after implant surgery. Immediate implant osseointegration can be successful in a patient with osteoporosis using bisphosphonates, suggesting the safety of implantology as a treatment modality. PMID:24041299

  19. Neurodevelopment at 1 year of age in infants with congenital heart disease

    PubMed Central

    Dittrich, H; Bührer, C; Grimmer, I; Dittrich, S; Abdul-Khaliq, H; Lange, P E

    2003-01-01

    Objective: To assess psychomotor development and neurological sequelae in infants after surgery for congenital heart defects. Design and setting: Single institution prospective cohort study. Patients: 90 of 112 consecutive surviving infants of less than 1 year of age, without brain anomalies, conditions, or syndromes associated with delayed mental development, who underwent cardiac surgery during an 18 month period; 20 control infants with minor or no congenital heart defects. Main outcome measures: Griffiths developmental scales and standardised neurological examination at 1 year. Results: Mean (SD) developmental quotient (DQ) in index infants was 99 (10.6), compared with 106.7 (6.6) in controls (p < 0.001). DQ was lower in infants after palliative surgery (n = 16; 88 (12.2)) than after corrective surgery (n = 74; 101.4 (8.6)) (p < 0.001). Of the 90 index infants, 24 (27%) had a DQ below 93.5 (more than 2 SD below the mean of controls). Developmental delay (DQ < 93.5) was more common after palliative surgery (10/16, 63%) than after corrective surgery (14/74, 19%) (p < 0.001). Of the 90 index infants, 29 (32%) had neurological abnormalities, compared with only one of the 20 controls (5%) (p = 0.013). Neurological abnormalities were more frequent after palliative surgery (11/16, 69%) than after corrective surgery (18/74, 24%) (p < 0.001). Conclusions: There is a considerable rate of neurodevelopmental impairment at 1 year of age in infants after cardiac surgery. Psychomotor impairment and neurological sequelae are apparently more severe in infants in whom only palliative surgery is possible. PMID:12639876

  20. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H.; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-01-01

    Abstract The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  1. Health Care Costs 1 Year After Pediatric Traumatic Brain Injury

    PubMed Central

    Rivara, Frederick P.; Vavilala, Monica S.

    2015-01-01

    Objectives. This study sought to estimate total health care costs for mild, moderate, and severe pediatric traumatic brain injury (TBI) and to compare individual- and population-level costs across levels of TBI severity. Methods. Using 2007 to 2010 MarketScan Commercial Claims and Encounters data, we estimated total quarterly health care costs 1 year after TBI among enrollees (aged < 18 years). We compared costs across levels of TBI severity using generalized linear models. Results. Mild TBI accounted for 96.6% of the 319 103 enrollees with TBI; moderate and severe TBI accounted for 1.7% and 1.6%, respectively. Adjusted individual health care costs for moderate and severe TBI were significantly higher than mild TBI in the year after injury (P < .01). At the population level, moderate and severe TBI costs were 88% and 75% less than mild TBI, respectively. Conclusions. Individually, moderate and severe TBI initially generated costs that were markedly higher than those of mild TBI. At the population level, costs following mild TBI far exceeded those of more severe cases, a result of the extremely high population burden of mild TBI. PMID:26270293

  2. Caregiver burden at 1 year following severe traumatic brain injury.

    PubMed

    Marsh, N V; Kersel, D A; Havill, J H; Sleigh, J W

    1998-12-01

    Sixty-nine primary caregivers of adults with a severe traumatic brain injury (TBI) were assessed at 1-year post-injury. Caregivers completed questionnaires on the physical, cognitive, emotional, behavioural, and social functioning of the person with TBI. Caregiver objective burden, psychosocial functioning, and subjective burden were also assessed. Clinically significant levels of anxiety and depression were evident in over a third of the caregivers. Similarly, a quarter of the caregivers reported poor social adjustment. There was no consistent relationship between the prevalence of various types of objective burden and the level of subjective distress that resulted from these changes. The person with TBI's emotional difficulties, in particular their anger, apathy, and dependency, caused the greatest distress for caregivers. With regard to the impact that caregiving had on their own lives, caregivers were most distressed by the loss of personal free time. Results from a regression analysis indicated that the person with TBI's physical impairment, number of behavioural problems, and social isolation were the strongest predictors of caregiver burden. The impact that caring for a person with severe TBI can have on the extended family unit is discussed. PMID:9876864

  3. Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

    SciTech Connect

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

    2008-05-01

    Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer.

  4. Varicella paediatric hospitalisations in Belgium: a 1-year national survey

    PubMed Central

    Blumental, Sophie; Sabbe, Martine; Lepage, Philippe

    2016-01-01

    Background Varicella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1-year period. Methods Data on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash. Results Participation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/105 person-years, with the highest impact among those 0–4 years old (global incidence and odds of hospitalisation: 79/105 person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had ≥1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/105 person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/106 and fatality ratio 0.2% among our cohort. Conclusions Varicella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium. PMID:26130380

  5. Weight changes in children in foster care for 1 year

    PubMed Central

    Schneiderman, Janet U.; Smith, Caitlin; Arnold, Janet S.; Fuentes, Jorge; Duan, Lei

    2013-01-01

    Objective The aims of this study of predominately racial/ethnic minority children in foster care (N = 360, birth to 19 years old) in Los Angeles, CA were to examine the (1) prevalence of obesity (≥ 95 percentile) and overweight/obese(≥ 85 percentile) upon entrance to foster care (T1) and after 1 year in foster care (T2); (2) comparison of high weight categories to national statistics; (3) relationship of changes in weight status to age, reason for entry into foster care, and placement. Methods Chi-square test and McNemar test comparing paired proportions were used to determine whether there were significant changes in the proportion of high weight categories between T1 and T2. Chi-square test or Fisher’s exact test were used to evaluated the association between age, placement, and reason for foster care with the change in weight category. Changes in weight were categorized as (1) decreased in weight, (2) remained at overweight or obese, (3) increased in weight, or (4) remained normal. Results The proportion of obese and obese/overweight children between age 2 and 5 were significantly lower at T2 than T1. There were no significant changes in the prevalence of obesity for the total population at T2. Children age 6 or older had a higher prevalence of obesity and overweight/obesity compared to national statistics. Of children at all ages, 64.7% of children of all ages entered foster care with a normal weight and stayed in the normal range during their first year in foster care, 12.2% decreased their weight, 15.4% remained overweight or obese, and 7.7% increased their weight. Age and parental substance use was related to change in weight category from T1 to T2. Conclusions Children did not become more overweight or obese in foster care; however 28% of the children were obese or overweight upon entry into foster care. Children who are 6 years or older and obese upon entering foster care should be targeted for weight reduction. The pediatric community and child

  6. Candle Flames in Microgravity: USML-1 Results - 1 Year Later

    NASA Technical Reports Server (NTRS)

    Ross, H. D.; Dietrich, D. L.; Tien, J. S.

    1994-01-01

    We report on the sustained behavior of a candle flame in microgravity determined in the glovebox facility aboard the First United States Microgravity Labomtofy. In a quiescent, microgmvjfy environment, diffusive transport becomes the dominant mode of heat and mass transfer; whether the diffusive transport rate is fast enough to sustain low-gravity candle flames in air was unknown to this series of about 70 tests. After an initial transient in which soot is observed, the microgravity candle flame in air becomes and remains hemispherical and blue (apparently soot-Ne) with a large flame standoff distance. Near flame extinction, spontaneous flame oscillations are regularly observed; these are explained as a flashback of flame through a premixed combustible gas followed by a retreat owed to flame quenching. The frequency of oscillations can be related to diffusive transport rates, and not to residual buoyant convective flow. The fact that the flame tip is the last point of the flame to survive suggests that it is the location of maximum fuel reactivity; this is unlike normal gravity, where the location of maximum fuel reactivity is the flame base. The flame color, size, and shape behaved in a quasi-steady manner; the finite size of the glovebox, combined with the restricted passages of the candlebox, inhibited the observation of true steady-state burning. Nonetheless, through calculations, and inference from the series of shuttle tests, if is concluded that a candle can burn indefinitely in a large enough ambient of air in microgravity. After igniting one candle, a second candle in close pximity could not be lit. This may be due to wax coating the wick and/or local oxygen depletion around the second, unlit candle. Post-mission testing suggests that simultaneous ignition may overcome these behaviors and enable both candles to be ignited.

  7. Long-term survival and functional status of patients with low-grade astrocytoma of spinal cord

    SciTech Connect

    Robinson, Clifford G.; Prayson, Richard A.; Hahn, Joseph F.; Kalfas, Iain H.; Whitfield, Melvin D.; Lee, S.-Y.; Suh, John H. . E-mail: suhj@ccf.org

    2005-09-01

    Purpose: To determine survival and changes in neurologic function and Karnofsky performance status (KPS) in a series of patients treated for low-grade astrocytoma of the spinal cord during the past two decades. Methods: This study consisted of 14 patients with pathologically confirmed low-grade astrocytoma of the spinal cord who were treated between 1980 and 2003. All patients underwent decompressive laminectomy followed by biopsy (n = 7), subtotal resection (n = 6), or gross total resection (n = 1). Ten patients underwent postoperative radiotherapy (median total dose 50 Gy in 28 fractions). The overall survival, progression-free survival, and changes in neurologic function and KPS were measured. Results: The overall survival rate at 5, 10, and 20 years was 100%, 75%, and 60%, respectively. The progression-free survival rate at 5, 10, and 20 years was 93%, 80%, and 60%, respectively. Neither overall survival nor progression-free survival was clearly correlated with any patient, tumor, or treatment factors. Neurologic function and KPS worsened after surgery in 8 (57%) of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2 years, neurologic function had stabilized or improved in 8 (73%) of 11 remaining patients, but the KPS had worsened in 5 (50%) of 10. Most patients who were employed before surgery were working at last follow-up. Conclusion: Patients who undergo gross total resection of their tumor may be followed closely. Patients who undergo limited resection should continue to receive postoperative RT (50.4 Gy in 1.8-Gy fractions). The functional measures should be routinely evaluated to appreciate the treatment outcomes.

  8. Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival

    PubMed Central

    Facchini, Gaetano; Caffo, Orazio; Ortega, Cinzia; D'Aniello, Carmine; Di Napoli, Marilena; Cecere, Sabrina C.; Della Pepa, Chiara; Crispo, Anna; Maines, Francesca; Ruatta, Fiorella; Iovane, Gelsomina; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Pignata, Sandro; Cavaliere, Carla

    2016-01-01

    Background: Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. Patients and Methods: We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. Results: We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6–6.5) and the median OS was 17.1 months (8.8–25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12–0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06–0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. Conclusion: A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS. PMID:27242530

  9. Motor Testing at 1 Year Improves the Prediction of Motor and Mental Outcome at 2 Years after Perinatal Hypoxic-Ischaemic Encephalopathy

    ERIC Educational Resources Information Center

    van Schie, Petra Em; Becher, Jules G.; Dallmeijer, Annet J.; Barkhof, Frederik; van Weissenbruch, Mirjam M.; Vermeulen, R. Jeroen

    2010-01-01

    Aim: To investigate the predictive value of motor testing at 1 year for motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy (HIE) in term neonates. Method: Motor and mental outcome at 2 years was assessed with the Bayley Scales of Infant Development, 2nd edition (BSID-II) in 32 surviving children (20 males, 12…

  10. Prognostic factors and survival in late adolescent and adult patients with small round cell tumors.

    PubMed

    Eralp, Yeşim; Bavbek, Sevil; Başaran, Mert; Kaytan, Esra; Yaman, Fulya; Bilgiç, Bilge; Darendeliler, Emin; Onat, Haluk

    2002-08-01

    The primary objective of this study is to review the clinical characteristics of 25 patients in the adult and late adolescent age group, diagnosed and treated with small round cell tumors involving soft tissues (extraosseous Ewing sarcoma, rhabdo-myosarcoma, primitive neuroectodermal tumor, and undiffer-entiated small round cell tumors). Additionally, survival and prognostic factors influencing the outcome with multimodality treatment are evaluated. There were 19 males (76%) and 6 females (24%). The median age was 26 years (range: 15-56 years). In 9 patients (36%), the tumor was located at an extremity, whereas 16 patients (64%) had central localizations. Tumor size was larger than 10 cm in 7 patients (29.2%). Six patients (24%) had metastatic disease. Twelve patients (48%) received radiation and 16 patients (64%) underwent surgery. Among the resected tumors, 2 were resected with contaminated margins (12.5%), whereas 2 were radically resected and 12 (75%) were resected with wide margins. All patients were given a median of 4 cycles of multiagent chemotherapy (1-14 cycles). With preoperative chemotherapy, complete regression (CR) of the tumor was achieved in 6 patients (24%). In 4 patients (16%), a partial response was obtained. After the completion of multimodality treatment, 12 patients (48%) had a CR. Progression-free (PFS) and overall survival (OS) for the entire group was 25.0 +/- 10.8% at 1 year and 30.5 +/- 15.5% at 3 years, respectively. Nonmetastatic disease, wide and radical resection, and presence of CR to multimodality treatment were associated with a significantly longer PFS and OS by univariate analysis. By multivariate analysis, CR to multimodality treat-ment was the only independent predictive factor for a longer OS (p: 0.0036, relative risk [RR]: 23.6, 95% CI: 2.8; 198.7) and metastatic presentation was the only independent factor predic-tive for a shorter PFS (p: 0.017, RR. 15, 95% CI: 1.6; 141.2). Large-scale, multicenter studies are required for

  11. Survival in MS

    PubMed Central

    Reder, A.T.; Ebers, G.C.; Cutter, G.; Kremenchutzky, M.; Oger, J.; Langdon, D.; Rametta, M.; Beckmann, K.; DeSimone, T.M.; Knappertz, V.

    2012-01-01

    Objective: To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. Methods: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNβ-1b 250 μg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary. Results: After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNβ-1b 250 μg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314–0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNβ-1b 250 μg–treated patients (46.0% among IFNβ-1b 50 μg–treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. Conclusions: There was a significant survival advantage in this cohort of patients receiving early IFNβ-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNβ-1b benefit on all-cause mortality. Classification of Evidence: This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis. PMID:22496198

  12. Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-02-09

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  13. Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology

    PubMed Central

    Sherrill, Beth; Kaye, James A; Sandin, Rickard; Cappelleri, Joseph C; Chen, Connie

    2012-01-01

    Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types. PMID:23109809

  14. Prevalence and 1-year prognosis of transient heart failure following coronary revascularization.

    PubMed

    Ambrosetti, Marco; Griffo, Raffaele; Tramarin, Roberto; Fattirolli, Francesco; Temporelli, Pier Luigi; Faggiano, Pompilio; De Feo, Stefania; Vestri, Anna Rita; Giallauria, Francesco; Greco, Cesare

    2014-09-01

    The occurrence of heart failure during the whole pre-discharge course of coronary revascularization, as far as its influence on subsequent prognosis, is poorly understood. The present study examined the effect of transient heart failure (THF) developing in the acute and rehabilitative phase on survival after coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI). Patients in the Italian survey on cardiac rehabilitation and secondary prevention after cardiac revascularization (ICAROS) were analyzed for THF, the latter being defined either as signs and symptoms consistent with decompensation or cardiogenic shock. ICAROS was a prospective, multicenter registry of 1,262 consecutive patients discharged from 62 cardiac rehabilitation (CR) facilities, providing data on risk factors, lifestyle habits, drug treatments, and major cardiovascular events (MACE) during a 1-year follow-up. Records were linked to the official website of the Italian Association of Cardiovascular Prevention and Rehabilitation (GICR-IACPR). The overall prevalence of pre-discharge THF was 7.6%, with 69.8% of cases in acute wards, 22.9% during CR, and 7.3% in both settings. THF affected more frequently patients with chronic cardiac condition (42.7 vs. 30.6%; p < 0.05), age ≥75 years (33.3 vs. 23.1%; p < 0.005), COPD (19.8 vs. 12.3%; p < 0.05), and chronic kidney disease (17.7 vs. 7%; p < 0.001). After discharge, THF patients showed good maintenance rates of RAAS modulators (90.6%) and beta-blockers (83.3%), while statin therapy significantly decreased from 81.3 to 64.6% (p < 0.05). The pursuit of secondary prevention targets, as far as self-reported drug adherence, was not different among groups. Patients with THF had increased 1-year mortality (8.3 vs. 1.6%, p < 0.001). Moreover, THF independently predicted adverse outcome with OR for recurrent events (mainly further episodes of decompensation) of 2.4 (CI 1.4-4.3). Patients who experienced THF after coronary

  15. [Retroperitoneal lymphadenectomy and survival of patients treated for an advanced ovarian cancer: the CARACO trial].

    PubMed

    Classe, J-M; Cerato, E; Boursier, C; Dauplat, J; Pomel, C; Villet, R; Cuisenier, J; Lorimier, G; Rodier, J-F; Mathevet, P; Houvenaeghel, G; Leveque, J; Lécuru, F

    2011-05-01

    The standard management for advanced-stage epithelial ovarian cancer is optimum cytoreductive surgery followed by platinum based chemotherapy. However, retroperitoneal lymph node resection remains controversial. The multiple directions of the lymph drainage pathway in ovarian cancer have been recognized. The incidence and pattern of lymph node involvement depends on the extent of the disease and the histological type. Several published cohorts suggest the survival benefit of pelvic and para-aortic lymphadenectomy. A recent large randomized trial have demonstrated the potential benefit for surgical removal of bulky lymph nodes in term of progression-free survival but failed to show any overall survival benefit because of a critical methodology. Further randomised trials are needed to balance risks and benefits of systematic lymphadenectomy in advanced-stage disease. CARACO is a French ongoing trial, built to bring a reply to this important question. A huge effort for inclusion of the patients, and involving new teams, are mandatory. PMID:21482037

  16. Is England closing the international gap in cancer survival?

    PubMed Central

    Walters, Sarah; Benitez-Majano, Sara; Muller, Patrick; Coleman, Michel P; Allemani, Claudia; Butler, John; Peake, Mick; Guren, Marianne Grønlie; Glimelius, Bengt; Bergström, Stefan; Påhlman, Lars; Rachet, Bernard

    2015-01-01

    Background: We provide an up-to-date international comparison of cancer survival, assessing whether England is ‘closing the gap' compared with other high-income countries. Methods: Net survival was estimated using national, population-based, cancer registrations for 1.9 million patients diagnosed with a cancer of the stomach, colon, rectum, lung, breast (women) or ovary in England during 1995–2012. Trends during 1995–2009 were compared with estimates for Australia, Canada, Denmark, Norway and Sweden. Clinicians were interviewed to help interpret trends. Results: Survival from all cancers remained lower in England than in Australia, Canada, Norway and Sweden by 2005–2009. For some cancers, survival improved more in England than in other countries between 1995–1999 and 2005–2009; for example, 1-year survival from stomach, rectal, lung, breast and ovarian cancers improved more than in Australia and Canada. There has been acceleration in lung cancer survival improvement in England recently, with average annual improvement in 1-year survival rising to 2% during 2010–2012. Survival improved more in Denmark than in England for rectal and lung cancers between 1995–1999 and 2005–2009. Conclusions: Survival has increased in England since the mid-1990s in the context of strategic reform in cancer control, however, survival remains lower than in comparable developed countries and continued investment is needed to close the international survival gap. PMID:26241817

  17. Prognostic factors and survival in patients with metastatic or recurrent carcinoma of the uterine cervix.

    PubMed

    Eralp, Y; Saip, P; Sakar, B; Kucucuk, S; Aydiner, A; Dincer, M; Aslay, I; Topuz, E

    2003-01-01

    The aim of this study is to identify the impact of various prognostic factors on survival in patients with recurrent carcinoma of the uterine cervix. Fifty-two patients who were treated with platinum-based chemotherapy for recurrent or metastatic disease were retrospectively evaluated. Twenty-seven patients (90%) had received pelvic radiation as primary treatment. Out of 45 evaluable patients, two (4.4%) had complete response (CR), three (6.7%) had a continuous CR after additional surgical treatment and irradiation. Five patients (11.1%) had partial response (PR). The majority of patients had progressive response to treatment (22 patients, 48.9%). After a median follow-up period of 19 months, 31 patients (60%) had died. Progression-free survival after initial diagnosis was observed to have a significant association with response to chemotherapy for recurrent disease (Fisher two-sided P = 0.027). The median survival duration for relapsed disease was 11.8 months. Those with a longer disease-free interval ( 8 months vs. survival duration after relapse by univariate analysis. Multivariate analysis revealed that progressive response to chemotherapy (P = 0.002, HR = 4.6) and recurrence within the previously irradiated field (P = 0.04, HR = 2.7) were significant independent prognostic factors for a shorter time to progression after recurrence. Furthermore, advanced stage at presentation (P = 0.001, HR = 3.0) and a short disease-free interval after primary treatment (<8 months, P = 0.003, HR = 3.4) were determined as independent prognostic factors with a significant negative influence on progression-free survival and overall survival from initial diagnosis, respectively. The use of toxic and expensive combinations for the treatment of recurrent cervical cancer patients should be well balanced against potential hazards. Based on our data, less toxic regimens

  18. IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

    PubMed Central

    Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

    2010-01-01

    Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

  19. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: A survival study

    PubMed Central

    Baruah, Upasana; Barmon, Debabrata; Kataki, Amal Chandra; Deka, Pankaj; Hazarika, Munlima; Saikia, Bhargab J.

    2015-01-01

    Context: Patients with advanced ovarian cancer have a poor prognosis in spite of the best possible care. Primary debulking surgery has been the standard of care in advanced ovarian cancer; however, it is associated with high mortality and morbidity rates as shown in various studies. Several studies have discussed the benefit of neoadjuvant chemotherapy in patients with advanced ovarian cancer. Aims: This study aims to evaluate the survival statistics of the patients who have been managed with interval debulking surgery (IDS) from January 2007 to December 2009. Materials and Methods: During the period from January 2007 to December 2009, a retrospective analysis of 104 patients who underwent IDS for stage IIIC or IV advanced epithelial ovarian cancer at our institute were selected for the study. IDS was attempted after three to five courses of chemotherapy with paclitaxal (175 mg/m2 ) and carboplatin (5-6 of area under curve). Overall survival (OS) and progression free survival (PFS) were compared with results of primary debulking study from existing literature. OS and PFS rates were estimated by means of the Kaplan-Meier method. Results were statistically analyzed by IBM SPSS Statistics 19. Results: The median OS was 26 months and the median PFS was 18 months. In multivariate analysis it was found that both OS and PFS was affected by the stage, and extent of debulking. Conclusions: Neoadjuvant chemotherapy, followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers. PMID:25810573

  20. First experiences with the direct anterior approach in lateral decubitus position: learning curve and 1 year complication rate.

    PubMed

    Melman, Wietse P R; Mollen, Bas P; Kollen, Boudewijn J; Verheyen, Cees C P M

    2015-01-01

    The direct anterior approach (DAA) in supine position for hip arthroplasty has been reported to suffer from high complication rates initially. The DAA with the patient in lateral decubitus position is believed to provide better visibility and especially femoral accessibility with potential fewer complications.The first cohort of total hip prostheses, which were implanted by a single surgeon using DAA in lateral decubitus position more than 1 year ago, was analysed retrospectively.In total 182 hip prostheses (172 patients) were analysed. Three consecutive time periods based on equal number of surgical procedures were compared. The technical complication rate and operating time improved significantly between the 3 consecutive groups. The 1 year infection rate was 0.5% and survival rate of 98.9%.This is the first series of patients that were subjected to a hip replacement based on the direct anterior approach in a lateral decubitus position in which decreasing complication rates suggest the presence of a learning curve in surgeons conducting this type of surgery. Initial complication rate was high but decreased significantly in time and was acceptable certainly in the third group of our cohort. An unacceptable complication rate with the straight uncemented stem forced us to discontinue this configuration after only 7 surgical procedures. Complication, infection and revision rates were acceptable for the all cemented hip replacements using a curved anatomical stem. PMID:25684251

  1. Consecutive Case Series of Healed Single-Molar Sites Immediately Restored with Wide-Diameter Implants: A 1-Year Evaluation

    PubMed Central

    Cherfane, Pierre; Sojod, Bouchra

    2016-01-01

    Introduction. To evaluate outcomes of wide-diameter (6 mm) implants immediately provisionalized with cement-retained single crowns in posterior molar sites. Materials and Methods. Forty-eight consecutive patients received a total of 53 moderately rough-surface, 6 mm diameter implants in healed sites. All implants were immediately provisionalized with a cement-retained provisional crown. Final prosthesis with cement-retained porcelain fused to metal crowns was delivered 3–6 months later. Patients were followed up for 1 year. Outcome measures were implant failures and success rate, complications, marginal bone levels, bone level changes, papilla index, bleeding on probing, and inflammation. Results. One patient was lost to follow-up. At one year, the implant survival and success rate were 98.1%. The mean marginal bone loss after 1 year was −0.17 ± 1.84 mm. Ideal papilla score was recorded at 83.8% of the sites. More than 95.6% of the sites showed no bleeding or inflammation. No procedure-related or device-related adverse events were reported. Conclusion. Wide-diameter (6 mm) implants can safely and successfully replace single posterior molars. Longer follow-up studies are necessary to evaluate the long-term success of these implants. PMID:27195008

  2. Consecutive Case Series of Healed Single-Molar Sites Immediately Restored with Wide-Diameter Implants: A 1-Year Evaluation.

    PubMed

    Antoun, Hadi; Cherfane, Pierre; Sojod, Bouchra

    2016-01-01

    Introduction. To evaluate outcomes of wide-diameter (6 mm) implants immediately provisionalized with cement-retained single crowns in posterior molar sites. Materials and Methods. Forty-eight consecutive patients received a total of 53 moderately rough-surface, 6 mm diameter implants in healed sites. All implants were immediately provisionalized with a cement-retained provisional crown. Final prosthesis with cement-retained porcelain fused to metal crowns was delivered 3-6 months later. Patients were followed up for 1 year. Outcome measures were implant failures and success rate, complications, marginal bone levels, bone level changes, papilla index, bleeding on probing, and inflammation. Results. One patient was lost to follow-up. At one year, the implant survival and success rate were 98.1%. The mean marginal bone loss after 1 year was -0.17 ± 1.84 mm. Ideal papilla score was recorded at 83.8% of the sites. More than 95.6% of the sites showed no bleeding or inflammation. No procedure-related or device-related adverse events were reported. Conclusion. Wide-diameter (6 mm) implants can safely and successfully replace single posterior molars. Longer follow-up studies are necessary to evaluate the long-term success of these implants. PMID:27195008

  3. Nivolumab Doubles Survival for Patients with HNSCC.

    PubMed

    2016-07-01

    In patients with head and neck squamous cell carcinoma refractory to platinum-based chemotherapy, those treated with nivolumab had a 30% reduction in the risk of death compared with those assigned to receive one of three single-agent chemotherapies, according to a recent phase III trial. In addition, 1-year survival among nivolumab recipients was double that of those who received a chemotherapeutic, the current standard of care. PMID:27217382

  4. Defensive platform size and survivability. [Platform survivability

    SciTech Connect

    Canavan, Gregory H.

    1988-06-01

    This report discusses the survivability of space platforms, concentrating on space based kinetic energy interceptors. It evaluates the efficacy of hardening, maneuver, self-defense, and deception in extending the survivability of platforms of varying sizes to expected threats, concluding that they should be adequate in the near and mid terms.

  5. Upregulation of chemokine receptor CCR10 is essential for glioma proliferation, invasion and patient survival

    PubMed Central

    Chen, Lingchao; Liu, Xing; Zhang, Hai-Yan; Du, Wenzong; Qin, Zhiyong; Yao, Yu; Mao, Ying; Zhou, Liangfu

    2014-01-01

    Human gliomas are characterized by their invasion of normal brain structures irrespective of their grade of malignancy. Tumor cell invasion share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptor CCR10 is highly expressed in human glioblastoma compared with control brain tissue. In vitro, signaling through CCL27-CCR10 mediates activation of p-Akt, and subsequently induces proliferation and invasive responses. Cell proliferation and invasion promoted by CCL27 were blocked by inhibition of p-Akt or CCR10. In vivo, down-regulation of CCR10 significantly impairs growth of glioma. Clinically, High CCR10 expression in GBM correlated with p-Akt, shorter overall survival and progression-free survival (P < 0.05). Together, these findings suggest that elevated CCR10 is a critical molecular event associated with gliomagenesis. PMID:25149529

  6. Association of response endpoints with survival outcomes in multiple myeloma

    PubMed Central

    Lonial, S; Anderson, K C

    2014-01-01

    Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide

  7. Association of response endpoints with survival outcomes in multiple myeloma.

    PubMed

    Lonial, S; Anderson, K C

    2014-02-01

    Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide

  8. Survivability Versus Time

    NASA Technical Reports Server (NTRS)

    Joyner, James J., Sr.

    2014-01-01

    Develop Survivability vs Time Model as a decision-evaluation tool to assess various emergency egress methods used at Launch Complex 39B (LC 39B) and in the Vehicle Assembly Building (VAB) on NASAs Kennedy Space Center. For each hazard scenario, develop probability distributions to address statistical uncertainty resulting in survivability plots over time and composite survivability plots encompassing multiple hazard scenarios.

  9. Preoperative statin use is not associated with improvement in survival after glioblastoma surgery.

    PubMed

    Bhavsar, S; Hagan, K; Arunkumar, R; Potylchansky, Y; Grasu, R; Dang, A; Carlson, R; Cowels, C; Arnold, B; Rahlfs, T F; Lipski, I; Walsh, C; Nguyen, A T; Feng, L; Cata, J P

    2016-09-01

    Cohort studies have suggested that the use of statins is associated with decreased risk of glioma formation and mortality. Here, a cohort of patients with glioblastoma multiforme (GBM) was analyzed to further investigate associations between preoperative use of statins and recurrence, and progression free and overall survival. Patients who had surgery for GBM (N=284) were followed up for a median of 18.1months. Seventy-eight patients were taking statins preoperatively while the rest were not. Cox proportional hazards models adjusted for several covariates of interest were applied before and after propensity score matching. Compared with statin users, those not taking the lipid-lowering drugs had similar progression free survival before (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26; p=0.68) and after propensity score matching (HR 0.95, 95% CI 0.67-1.35; p=0.68). Mortality was similar between both groups of patients before (HR 0.94, 95% CI 0.70-1.22; p= 0.73) and after propensity score matching (HR 1.13, 95% CI 0.78-1.64; p=0.49). Age and dexamethasone use were independent prognostic factors of survival. Contrary to previously published evidence, this study could not find an association between preoperative statin use and longer survival in GBM patients. Due to the small number of patients and retrospective nature of the study, further work is needed to understand the role of perioperative statins in GBM patients. PMID:27396375

  10. Primary Tumor Resection and Survival in Patients with Stage IV Gastric Cancer

    PubMed Central

    Mutlu, Hasan; Karaağaç, Mustafa; Eryilmaz, Melek Karakurt; Gündüz, Şeyda; Artaç, Mehmet

    2016-01-01

    Purpose The aim of this study was to determine whether surgical resection of the primary tumor contributes to survival in patients with metastatic gastric cancer. Materials and Methods A total of 288 patients with metastatic gastric cancer from the Akdeniz University, Antalya Training and Research Hospital, and the Meram University of Konya database were retrospectively analyzed. The effect of primary tumor resection on survival of patients with metastatic gastric cancer was investigated using the log-rank test. Kaplan-Meier survival estimates were calculated. Multivariate analysis was performed using Cox proportional hazards regression modeling. Results The median overall survival was 12.0 months (95% confidence intewrval [CI], 10.4~13.6 months) and 7.8 months (95% CI, 5.5~10.0 months) for patients with and without primary tumor resection, respectively (P<0.001). The median progression-free survival was 8.3 months (95% CI, 7.1~9.5 months) and 6.2 months (95% CI, 5.8~6.7 months) for patients with and without primary tumor resection, respectively (P=0.002). Conclusions Non-curative gastrectomy in patients with metastatic gastric cancer might increase their survival rate regardless of the occurrence of life-threatening tumor-related complications. PMID:27433392

  11. Surviving Atmospheric Spacecraft Breakup

    NASA Technical Reports Server (NTRS)

    Szewczyk, Nathaniel J.; Conley, Catharine A.

    2003-01-01

    In essence, to survival a spacecraft breakup an animal must not experience a lethal event. Much as with surviving aircraft breakup, dissipation of lethal forces via breakup of the craft around the organism is likely to greatly increase the odds of survival. As spacecraft can travel higher and faster than aircraft, it is often assumed that spacecraft breakup is not a survivable event. Similarly, the belief that aircraft breakup or crashes are not survivable events is still prevalent in the general population. As those of us involved in search and rescue know, it is possible to survive both aircraft breakup and crashes. Here we make the first report of an animal, C. elegans, surviving atmospheric breakup of the spacecraft supporting it and discuss both the lethal events these animals had to escape and the implications implied for search and rescue following spacecraft breakup.

  12. Conditional Probability of Survival in Patients With Newly Diagnosed Glioblastoma

    PubMed Central

    Polley, Mei-Yin C.; Lamborn, Kathleen R.; Chang, Susan M.; Butowski, Nicholas; Clarke, Jennifer L.; Prados, Michael

    2011-01-01

    Purpose The disease outcome for patients with cancer is typically described in terms of estimated survival from diagnosis. Conditional probability offers more relevant information regarding survival for patients once they have survived for some time. We report conditional survival probabilities on the basis of 498 patients with glioblastoma multiforme receiving radiation and chemotherapy. For 1-year survivors, we evaluated variables that may inform subsequent survival. Motivated by the trend in data, we also evaluated the assumption of constant hazard. Patients and Methods Patients enrolled onto seven phase II protocols between 1975 and 2007 were included. Conditional survival probabilities and 95% CIs were calculated. The Cox proportional hazards model was used to evaluate prognostic values of age, Karnofsky performance score (KPS), and prior progression 1-year post diagnosis. To assess the constant hazard assumption, we used a likelihood-ratio test to compare the Weibull and exponential distributions. Results The probabilities of surviving an additional year given survival to 1, 2, 3, and 4 years were 35%, 49%, 69%, and 93%, respectively. For patients who survived for 1 year, lower KPS and progression were significantly predictive of shorter survival (both P < .001), but age was not (hazard ratio, 1.22 for a 10-year increase; P = .25). The Weibull distribution fits the data significantly better than exponential (P = .02), suggesting nonconstant hazard. Conclusion Conditional probabilities provide encouraging information regarding life expectancy to survivors of glioblastoma multiforme. Our data also showed that the constant hazard assumption may be violated in modern brain tumor trials. For single-arm trials, we advise using individual patient data from historical data sets for efficacy comparisons. PMID:21969507

  13. Restoration of the Ellipsoid Zone and Visual Prognosis at 1 Year after Surgical Macular Hole Closure

    PubMed Central

    Hasebe, Hiruma; Matsuoka, Naoki; Terashima, Hiroko; Sasaki, Ryo; Ueda, Eriko; Fukuchi, Takeo

    2016-01-01

    Purpose. To evaluate the restoration of the ellipsoid zone (EZ) and its influence on visual prognosis 1 year after surgical macular hole (MH) closure. Method. Subjects were patients with stage 2, 3, or 4 idiopathic MH who underwent primary vitrectomy that resulted in successful hole closure. Nineteen eyes with both EZ disruption with foveal detachment and a continuous external limiting membrane on optical coherence tomography during the early postoperative period were included in this study. Result. EZ disruption was restored in 10 eyes (53%, Group A) and remained in 9 eyes (47%, Group B) at 1 year after surgery. In Group B, the diameter of the residual EZ disruption was 54.7 ± 33.1 μm. LogMAR visual acuity (VA) 1 year after surgery was significantly better than preoperative VA in each group (Group A: −0.007 ± 0.102; P < 0.001; Group B: 0.051 ± 0.148; P < 0.001), but there was no significant difference between the 2 groups (P = 0.332). There was no significant correlation between logMAR VA and EZ disruption diameter at 1 year after surgery. Conclusion. EZ was restored in 53% of eyes at 1 year after surgical closure of idiopathic MH. Mean residual EZ disruption diameter was 54.7 ± 33.1 μm. Neither resolved nor residual EZ disruption influenced postoperative VA. PMID:26941999

  14. Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

    PubMed

    Zolal, Amir; Juratli, Tareq A; Linn, Jennifer; Podlesek, Dino; Sitoci Ficici, Kerim Hakan; Kitzler, Hagen H; Schackert, Gabriele; Sobottka, Stephan B; Rieger, Bernhard; Krex, Dietmar

    2016-05-01

    Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis. PMID:26830088

  15. A postoperative 1-Year eGFR of More Than 45 ml/min May be the Cutoff Level for a Favorable Long-Term Prognosis in Renal Transplant Patients.

    PubMed

    Baek, Chung Hee; Kim, Hyosang; Yang, Won Seok; Han, Duck Jong; Park, Su-Kil

    2016-01-01

    BACKGROUND One-year renal function after kidney transplantation (KT) classified by the Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) staging has been reported to be associated with graft survival. However, the outcomes of KT are improving. Therefore, the distribution and prognostic value of 1-year estimated glomerular filtration rate (eGFR) in recently performed transplants were re-evaluated in this study. MATERIAL AND METHODS We reviewed all patients who received KT between 2008 and 2011 at our institution, and followed them until June 2015. The distribution of 1-year eGFR, graft survival according to CKD staging, the cutoff level for a favorable prognosis, and the occurrence of rejection and infection were analyzed. RESULTS A total of 758 patients were included in this study. Unlike previous studies, most patients (56.2%) were in the CKD stage 2 (eGFR 60-89) rather than stage 3 (eGFR 30-59). In addition, the CKD stage 3a (eGFR 45-59) group showed better graft survival than the CKD stage 3b (eGFR 30-44) group. However, CKD stage 2 and CKD stage 3a groups did not show significant differences in graft survival. Patients with postoperative 1-year eGFR ≥45 ml/min showed a more favorable outcome compared with those with postoperative 1-year eGFR <45 ml/min. One-year eGFR<45 ml/min, acute cellular rejection, antibody-mediated rejection, and CMV infection after 1 year were adjusted risk factors for graft failure. CONCLUSIONS A 1-year eGFR ≥45 ml/min may be the appropriate cutoff level for predicting favorable outcomes in KT. In addition, KDIGO CKD staging may no longer be useful in recently performed KT. PMID:27418011

  16. Evaluation of the management of Hr-HPV+/PapTest- women: results at 1-year recall

    PubMed Central

    Chiappetta, Caterina; Puggioni, Chiara; Lendaro, Eugenio; Cacciotti, Jessica; Zaralli, Roberto; Migliore, Giovanna; Bellardini, Paola; Petrozza, Vincenzo; Della Rocca, Carlo; Di Cristofano, Claudio

    2015-01-01

    With cervical cancer screening the choice of 1-year as a period of follow-up in positive high-risk HPV women without cytological lesions is still under discussion. We evaluated the management of these women and the role of HPV genotyping test. We did a cervical cancer screening study of women aged 35-64 with primary high-risk HPV test. Women positive for high-risk HPV with negative cytology were followed-up after 1 year. In this study we selected women with high-risk HPV+/PapTest- resulted high-risk HPV+ at recall and performed the PapTest and HPV genotyping test. The detection rate of squamous high grade (CIN2+) relative to the total screened cohort was 2.1‰, and it was 0.2‰ at the 1-year recall. The colposcopy performed in women referred at the 1-year recall accounted for 48.8% of the total (baseline + 1-year recall), and 84.3% of these women had no cytological lesions. The most frequent hr-HPV genotype detected was HPV16 and 66.7% of co-infections were due to HPV16 and HPV18. 54.5% of women presented a persistent infection at 1-year recall with the same HPV subtype, 50% of persistent infections was due to HPV16 and 16.7% of these were determined to be CIN2+ histological lesions. Our data show that it may be useful to extend the period of follow-up for women hr-HPV+/PapTest- so as to reduce the number of unnecessary colposcopies due to the transitory infections and that the genotyping test could help to identify the persistent infections in which HPV16 is involved. PMID:26884886

  17. Clinical differences between opioid abuse classes ameliorated after 1 year of buprenorphine-medication assisted treatment.

    PubMed

    Tkacz, Joseph; Severt, Jamie; Kassed, Cheryl; Ruetsch, Charles

    2012-01-01

    This study compared the clinical and demographic profiles of three opioid-dependent user groups, and measured their response to 1 year of buprenorphine-medication assisted treatment. Opioid prescription, street, and combination (street + prescription) users completed the Addiction Severity Index multiple times over the course of one treatment year. Although groups differed on all measured demographics (P values <.05) and on six of seven Addiction Severity Index composite scores at induction (P values <.05), differences were ameliorated after 1 year. Findings highlight the disparities between the various opioid-dependent patient subpopulations and suggest that buprenorphine-medication assisted treatment is an effective treatment across user subtypes. PMID:22540432

  18. Clinicopathologic and Survival Characteristics of Malignant Pleural Mesothelioma Registered in Hospital Cancer Registry

    PubMed Central

    Najmi, Kosar; Khosravi, Adnan; Seifi, Sharare; Chaibakhsh, Samira; Radmand, Golnar; Khodadad, Kian

    2014-01-01

    Background Malignant pleural mesothelioma (MPM) is a rare but fatal thoracic tumor, which in the majority of patients is caused by prolonged exposure to asbestos fibers. We aimed at presenting clinicopathological and treatment outcomes of 60 patients of MPM registered in our hospital cancer registry. Materials and Methods Demographic characteristics of patients, exposure to asbestos, smoking habit, their clinicopathologic characteristics and survival analysis were described. Results Sixty patients had MPM. Forty patients (66.7%) were men. The mean age of patients was 55.8±11 years. Chest pain and dyspnea were the most prevalent symptoms (31.7%, and 30%, respectively). Thirty-six (61.7%) patients reported asbestos exposure. The median survival and Progression free survival (PFS) were 10.5 months (0.95CI=9.22-11.78) and 7.57 months (0.95CI=5.68-9.45), respectively. In multivariate analysis, exposure to asbestos and epithelioid subtype significantly extended the survival time. Bilateral involvement, high blood level of LDH and platelet count ≥400,000 significantly shortened the overall survival. Conclusion MPM is still an important health problem in Iran. Given the aforementioned results, developing a national program to eliminate asbestos-related diseases according to the world health organization (WHO) recommendation is necessary. PMID:25506370

  19. 1-year retention rates and performance ratings: comparing associate degree, baccalaureate, and accelerated baccalaureate degree nurses.

    PubMed

    Weathers, Suzanne M; Raleigh, Edith D Hunt

    2013-09-01

    The purpose of this study was to examine 1-year retention and managerial performance ratings of newly licensed RNs (NLRNs) according to nursing education program types (associate degree, traditional baccalaureate, and accelerated 2nd degree baccalaureate). Findings revealed retention and performance differences, suggesting the possibility of tradeoffs related to educational program type when selecting NLRNs for open positions. PMID:23958525

  20. Randomized Trial of a Gatekeeper Program for Suicide Prevention: 1-Year Impact on Secondary School Staff

    ERIC Educational Resources Information Center

    Wyman, Peter A.; Brown, C. Hendricks; Inman, Jeff; Cross, Wendi; Schmeelk-Cone, Karen; Guo, Jing; Pena, Juan B.

    2008-01-01

    Gatekeeper-training programs, designed to increase identification and referral of suicidal individuals, are widespread but largely untested. A group-based randomized trial with 32 schools examined impact of Question, Persuade, Refer (QPR) training on a stratified random sample of 249 staff with 1-year average follow-up. To test QPR impact, the…

  1. Thai Adolescent Survivors 1 Year after the 2004 Tsunami: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Tuicomepee, Arunya; Romano, John L.

    2008-01-01

    This study examined the impact of the 2004 Asian tsunami on 400 Thai adolescents 1 year after the disaster. Quantitative analyses showed that youth behavior problems were positively associated with tsunami experiences and negatively associated with positive family functioning. Tsunami exposure, school connectedness, religious beliefs and…

  2. The Stability and Structure of Career Decision-Making Profiles: A 1-Year Follow-Up

    ERIC Educational Resources Information Center

    Gati, Itamar; Levin, Nimrod

    2012-01-01

    The Career Decision-Making Profile (CDMP) questionnaire is a multidimensional measure of the way individuals make career decisions, developed as an alternative to the single, most-dominant trait approach. Using a sample of freshmen students, the 2-week reliability (N = 273) and 1-year stability (N = 182) of the CDMP was tested for each of the 12…

  3. A Program To Promote Positive Body Image: A 1-Year Follow-Up Evaluation.

    ERIC Educational Resources Information Center

    McVey, Gail L.; Davis, Ron

    2002-01-01

    Evaluated the effectiveness of a program designed to promote body image satisfaction and prevent eating problems in young adolescent girls over a 1-year period. Found no program effect. Found instead, significant increases in body image satisfaction and decreases in eating problem scores over time for participants in both the prevention and…

  4. An Analysis of 1-Year Impacts of Youth Transition Demonstration Projects

    ERIC Educational Resources Information Center

    Fraker, Thomas M.; Luecking, Richard G.; Mamun, Arif A.; Martinez, John M.; Reed, Deborah S.; Wittenburg, David C.

    2016-01-01

    This article examines the impacts of the Youth Transition Demonstration, an initiative of the Social Security Administration (SSA) to improve employment outcomes for youth with disabilities. Based on a random assignment design, the analysis uses data from a 1-year follow-up survey and SSA administrative records for 5,203 youth in six research…

  5. Participation as a leader in immersion weight loss treatment: a 1-year follow-up study.

    PubMed

    Anderson, L M; Schaumberg, K; Anderson, D A; Kirschenbaum, D S

    2016-02-01

    Non-overweight individuals may follow aggressive weight management approaches alongside overweight/obese friends or family members; thus, research has begun to evaluate subsequent effects among non-overweight populations. A prior study evaluated the short-term effects of an immersion weight loss programme on healthy young adult staff leaders. Results indicated that participation seemed to benefit, not harm, the young adults. The current investigation examined 1-year eating disorder and weight trajectories in this sample. The total sample (N = 244) consisted of staff leaders (44.3%) and demographically similar comparison participants who completed eating disorder and weight assessments across four time points: baseline, end of summer, 6-week follow-up and 1-year follow-up. Forty-seven per cent of the original sample responded to all time points (staff leaders n = 60; comparison n = 55). Over the course of 1 year, risk trajectories did not differ between groups. Staff leaders did not report significant changes in body mass index, suggesting that they maintained healthy weight over the course of 1 year. Participation as an immersion weight loss programme leader appeared to be protective against weight gain, without increasing eating disorder risk, for healthy young adults. This provides further support for using weight management interventions across a wide range of individuals. PMID:26638779

  6. A rare case of peripheral T-cell lymphoma in 1-year-old child

    PubMed Central

    Kandakumar, Vignesh; Ganesan, Prasanth; Bajpai, Peush; Rajendranath, Rejiv; Tenali, Sagar; Majhi, Urmila; Sivaprakasam, Ponni

    2011-01-01

    Peripheral T-cell lymphoma (PTCL) represents approximately 12% of lymphoid neoplasms. They are even rarer in children and represent only 1% of Non-Hodgkin's lymphoma in this age group. We report a case of PTCL in a 1-year-old female child for its rarity. PMID:22563159

  7. Dialectical Behavior Therapy for Adolescents with Bipolar Disorder: A 1-Year Open Trial

    ERIC Educational Resources Information Center

    Goldstein, Tina R.; Axelson, David A.; Birmaher, Boris; Brent, David A.

    2007-01-01

    Objective: To describe an adapted version of dialectical behavior therapy for adolescents with bipolar disorder. Method: The dialectical behavior therapy intervention is delivered over 1 year and consists of two modalities: family skills training (conducted with individual family units) and individual therapy. The acute treatment period (6 months)…

  8. Levels of Phonological Awareness in Korean and English: A 1-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Cho, Jeung-Ryeul; McBride-Chang, Catherine

    2005-01-01

    The present study examined associations of levels of phonological awareness to word recognition in Korean and English in a 1-year longitudinal study of 91 children from Masan, Korea. With performances on tasks of speeded naming, vocabulary, and Korean Hangul in 2nd grade statistically controlled, only Korean syllable deletion predicted unique…

  9. Verbal Labels Modulate Perceptual Object Processing in 1-Year-Old Children

    ERIC Educational Resources Information Center

    Gliga, Teodora; Volein, Agnes; Csibra, Gergely

    2010-01-01

    Whether verbal labels help infants visually process and categorize objects is a contentious issue. Using electroencephalography, we investigated whether possessing familiar or novel labels for objects directly enhances 1-year-old children's neural processes underlying the perception of those objects. We found enhanced gamma-band (20-60 Hz)…

  10. Latent Classes of Adolescent Posttraumatic Stress Disorder Predict Functioning and Disorder after 1 Year

    ERIC Educational Resources Information Center

    Ayer, Lynsay; Danielson, Carla Kmett; Amstadter, Ananda B.; Ruggiero, Ken; Saunders, Ben; Kilpatrick, Dean

    2011-01-01

    Objective: To identify latent classes of posttraumatic stress disorder (PTSD) symptoms in a national sample of adolescents, and to test their associations with PTSD and functional impairment 1 year later. Method: A total of 1,119 trauma-exposed youth aged 12 through 17 years (mean = 14.99 years, 51% female and 49% male) participating in the…

  11. Endoscopic sleeve gastroplasty with 1-year follow-up: factors predictive of success

    PubMed Central

    Lopez-Nava, G.; Galvao, M.; Bautista-Castaño, I.; Fernandez-Corbelle, J. P.; Trell, M.

    2016-01-01

    Background and study aims: Bariatric endoscopy has emerged as an aid in the nonsurgical treatment of obesity. The objective of this study is to critically provide the results and follow-up of endoscopic sleeve gastroplasty 1 year after the procedure. Patients and methods: Prospective single-center follow-up study of 25 patients (5 men, 20 women) who underwent flexible endoscopic suturing for endoluminal gastric volume reduction. A multidisciplinary team provided post-procedure care. Patient outcomes were recorded at 1 year after the procedure. Linear regression analysis was done to evaluate the variables associated with best results at 1 year of follow-up. Results: Mean body mass index (BMI) was 38.5 ± 4.6 kg/m2 (range 30 – 47) and mean age 44.5 ± 8.2 years (range 29 – 60). At 1 year, 22 patients continued with the follow-up (2 dropped out at 6 months and 1 at 3 months). There were no major intra-procedural, early, or delayed adverse events. Mean BMI loss was 7.3 ± 4.2 kg/m2, and mean percentage of total body weight loss was 18.7 ± 10.7 at 1 year. In the linear regression analysis, adjusted by initial BMI, variables associated with %TBWL involved the frequency of nutritional (β = 0.563, P = 0.014) and psychological contacts (β = 0.727, P = 0.025). The number of nutritional and psychological contacts were predictive of good weight loss results. Conclusions: Endoscopic sleeve gastroplasty is a feasible, reproducible, and effective procedure to treat obesity. Nutritional and psychological interaction are predictive of success. PMID:26878054

  12. Occupational Survival Skills

    ERIC Educational Resources Information Center

    Leach, James A.; Nelson, Robert E.

    1978-01-01

    The author describes a set of twelve curriculum modules called "Occupational Survival Skills" relating to the "human" aspects of work organizations. The modules were based on information from opinion surveys of workers, students, parents, and teachers on what occupational survival skills are and how to teach them. (MF)

  13. Survival of young American alligators on a Florida lake

    USGS Publications Warehouse

    Woodward, A.R.; Hines, T.C.; Abercrombie, C.L.; Nichols, J.D.

    1987-01-01

    A capture-recapture study was conducted on Orange Lake, Florida, from 1979 through 1984 to estimate survival rates of young in an American alligator (Alligator mississippiensis) populations. Hatchlings remained together in sibling groups (pods) for at least their 1st year and then began to disperse during their 2nd spring and summer. Mortality through mid-November of their 1st year was negligible. Jolly-Seber (JS) survival estimates of hatchlings for 6 and 12 months were 76 and 41%, respectively. The 2-year JS estimate for the 1980 cohort was 8%. Minimum-Known-Alive (MKA) survival values were 72 and 46% of JS estimates for 6 months and 1 year of age. Survival during the 2nd 6 months of life (spring-summer) tended to be lower than survival during the 1st 6 months (fall-winter).

  14. Association of clinical and pathological variables with survival in thymoma.

    PubMed

    Aydiner, Adnan; Toker, Alper; Sen, Fatma; Bicakci, Ercan; Saglam, Esra Kaytan; Erus, Suat; Eralp, Yesim; Tas, Faruk; Oral, Ethem Nezih; Topuz, Erkan; Dilege, Sukru

    2012-09-01

    Our aim was to evaluate clinical and pathological features in prognosis of thymoma patients with particular emphasis on patients with myasthenia gravis (MG). From 1995 to 2010, 140 thymoma patients (women/men: 63/77) with a median age of 46 years (11-80 years) were admitted to our institution. According to World Health Organization (WHO), there were 23 (17%) type A, 12 (9%) type AB, 24 (17%) type B1, 42 (31%) type B2 and 36 (26%) type B3. The distribution of Masaoka stages I, II, III and IV was 24 (17%), 71 (51%), 18 (13%) and 27 (19%), respectively. MG coexisted in 61% of patients. After a mean follow-up of 34 months (1-158 months), 102 (73%) patients are alive and well while 14 (10%) are alive with disease. Twenty-three patients (16%) have died, only 9 died of thymoma. In univariate analyses, completeness of resection (P < .001), WHO histology (P = .008), Masaoka stage (P < .001) and MG (P = .002) were significant prognostic factors for progression-free survival (PFS). Young age (P = .008); Masaoka stages 1 and 2 (P = .039); WHO types A, AB and B1 (P = .031); complete resection (P = .024) and presence of MG (P = .05) significantly correlated with overall survival (OS). In multivariate analysis, Masaoka stages 1 and 2 (P = .038) and presence of MG (P = .01) were significantly correlated with a longer PFS; MG (P = .021) and WHO subtype (P = .022) were found to be significant prognostic factors for OS. Adjuvant radiotherapy improved neither OS nor PFS in completely resected stage 2 thymoma. Masaoka staging, WHO and MG are major determinants of prognosis in Turkish thymoma patients. Additionally, radiotherapy did not provide survival advantage to stage 2 patients with complete resection. PMID:22057358

  15. Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival12

    PubMed Central

    Jönsson, Jenny-Maria; Skovbjerg Arildsen, Nicolai; Malander, Susanne; Måsbäck, Anna; Hartman, Linda; Nilbert, Mef; Hedenfalk, Ingrid

    2015-01-01

    Background and Aims: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival in epithelial ovarian cancer. Methods: Immunohistochemical stainings for ERα, ERβ, PR, and AR were assessed in relation to survival in 118 serous and endometrioid ovarian cancers. Expression of the genes encoding the four receptors was studied in relation to prognosis in the molecular subtypes of ovarian cancer in an independent data set, hypothesizing that the expression levels and prognostic impact may differ between the subtypes. Results: Expression of PR or AR protein was associated with improved 5-year progression-free (P = .001 for both) and overall survival (P < .001 for both, log-rank test). ERα and ERβ did not provide prognostic information. Patients whose tumors coexpressed PR and AR had the most favorable prognosis, and this effect was retained in multivariable analyses. Analyses of the corresponding genes using an independent data set revealed differences among the molecular subtypes, but no clear relationship between high coexpression of PGR and AR and prognosis. Conclusions: A favorable outcome was seen for patients whose tumors coexpressed PR and AR. Gene expression data suggested variable effects in the different molecular subtypes. These findings demonstrate a prognostic role for PR and AR in ovarian cancer and support that tumors should be stratified based on molecular as well as histological subtypes in future studies investigating the role of endocrine treatment in ovarian cancer. PMID:26500033

  16. Immunologic Autograft Engineering and Survival in Non-Hodgkin Lymphoma.

    PubMed

    Porrata, Luis F; Burgstaler, Edwin A; Winters, Jeffrey L; Jacob, Eapen K; Gastineau, Dennis A; Suman, Vera J; Inwards, David J; Ansell, Stephen M; Micallef, Ivana N; Johnston, Patrick B; Nevala, Wendy; Markovic, Svetomir N

    2016-06-01

    Retrospective studies have reported that the collected and infused autograft absolute lymphocyte count (A-ALC) affects clinical outcomes after autologous peripheral hematopoietic stem cell transplantation (APHSCT). We hypothesized that manipulation of the apheresis machine to target a higher A-ALC dose would translate into prolonged progression-free survival (PFS) in patients with non-Hodgkin lymphoma (NHL) undergoing APHSCT. Between December 2007 and October 2010, we performed a double-blind, phase III, randomized study randomly assigning 122 patients with NHL to undergo collection with the Fenwal Amicus Apheresis system with our standard settings (mononuclear cells offset of 1.5 and RBC offset of 5.0) or at modified settings (mononuclear cells offset of 1.5 and RBC of 6.0). The primary endpoint was PFS. Neither PFS (hazard ratio [HR] of modified to standard, 1.13; 95% confidence interval [CI], .62 to 2.08; P = .70) nor overall survival (OS) (HR modified to standard, .85; 95% CI, .39 to 1.86; P = .68) were found to differ by collection method. Collection of A-ALC between both methods was similar. Both PFS (P = .0025; HR, 2.77; 95% CI, 1.39 to 5.52) and OS (P = .004; HR, 3.38; 95% CI, 1.27 to 9.01) were inferior in patients infused with an A-ALC < .5 × 10(9) lymphocytes/kg compared with patients infused with an A-ALC ≥ .5 × 10(9) lymphocytes/kg, regardless of the method of collection. We did not detect significant differences in clinical outcomes or in the A-ALC collection between the modified and the standard Fenwal Amicus settings; however, despite physician discretion on primary number of collections and range of cells infused, higher A-ALC infused dose were associated with better survival after APHSCT. PMID:26826432

  17. Early Neuropsychological Tests as Correlates of Productivity 1 Year after Traumatic Brain Injury: A Preliminary Matched Case-Control Study

    ERIC Educational Resources Information Center

    Ryu, Won Hyung A.; Cullen, Nora K.; Bayley, Mark T.

    2010-01-01

    This study explored the relative strength of five neuropsychological tests in correlating with productivity 1 year after traumatic brain injury (TBI). Six moderate-to-severe TBI patients who returned to work at 1-year post-injury were matched with six controls who were unemployed after 1 year based on age, severity of injury, and Functional…

  18. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA

    PubMed Central

    Fitoussi, Olivier; Belhadj, Karim; Mounier, Nicolas; Parrens, Marie; Tilly, Hervé; Salles, Gilles; Feugier, Pierre; Ferme, Christophe; Ysebaert, Loic; Gabarre, Jean; Herbrecht, Raoul; Janvier, Maud; Van Den Neste, Eric; Morschhauser, Franck; Casasnovas, Olivier; Ghesquieres, Hervé; Anglaret, Bruno; Brechignac, Sabine; Haioun, Corinne; Gisselbrecht, Christian

    2011-01-01

    Background As rituximab combined with CHOP improves complete remission and overall survival in diffuse large B-cell lymphoma, intensified chemotherapy followed by autologous stem-cell transplantation has also been advocated for high-risk patients. The aim of this study was to establish whether or not combining rituximab with high-dose chemotherapy and auto-transplantation also benefits patient survival. Design and Methods The LNH2003-3 study was a phase II trial including diffuse large B-cell lymphoma patients with 2 or 3 International Prognostic Index factors. They received four cycles of intensive biweekly chemotherapy with rituximab, doxorubicine, cyclophosphamide, vindesine, bleomycine, prednisolone (R-ACVBP) followed by auto-transplantation in responding patients. Two hundred and nine patients under 60 years of age were included in the study and 155 responding patients underwent auto-transplantation. In addition, a case-control study was performed by matching (1:1) 181 patients treated with R-ACVBP with ACVBP patients not given rituximab but submitted to auto-transplantation from the previous LNH1998-3 trial. Results With a median follow up of 45 months, 4-year progression-free survival and overall survival were estimated at 76% (CI: 69–81) and 78% (CI: 72–83), respectively. There was no difference between patients with 2 or 3 International Prognostic Index factors. Four year progression-free survival was significantly higher in R-ACVBP than ACVBP patients (74% vs. 58%; P=0.0005). There was also a significant increase in 4-year overall survival (76% vs. 68%; P=0.0494). Conclusions In high-risk diffuse large B-cell lymphoma patients, treatment with R-ACVBP followed by auto-transplantation results in a 78% 4-year overall survival which should be compared to other approaches. (Clinicaltrials.gov identifier: NCT00144807) PMID:21546499

  19. Less is still more: maintenance of the very brief exposure effect 1 year later.

    PubMed

    Siegel, Paul; Warren, Richard

    2013-04-01

    This study tested the hypothesis that an immediate effect of exposure to masked phobic stimuli on avoidance of the corresponding feared object would be maintained 1 year later. Fifty-three spider-phobic participants were identified with a questionnaire and a Behavioral Avoidance Test (BAT) with a live tarantula. One week later, they were administered 1 of 3 types of exposure: very brief (25-ms, masked) or clearly visible (125-ms, unmasked) images of spiders, or very brief images of flowers. They engaged in the BAT again immediately thereafter. One year later, they returned for a follow-up BAT. The immediate effect of exposure to very brief spiders on reducing avoidance of the tarantula was still evident 1 year later. Endurance of an effect by masked stimuli of this duration has not been reported before. Potential theoretical implications are discussed. PMID:23527506

  20. Supratentorial hemispheric ependymomas: an analysis of 109 adults for survival and prognostic factors.

    PubMed

    Hollon, Todd; Nguyen, Vincent; Smith, Brandon W; Lewis, Spencer; Junck, Larry; Orringer, Daniel A

    2016-08-01

    OBJECTIVE Survival rates and prognostic factors for supratentorial hemispheric ependymomas have not been determined. The authors therefore designed a retrospective study to determine progression-free survival (PFS), overall survival (OS), and prognostic factors for hemispheric ependymomas. METHODS The study population consisted of 8 patients from our institution and 101 patients from the literature with disaggregated survival information (n = 109). Patient age, sex, tumor side, tumor location, extent of resection (EOR), tumor grade, postoperative chemotherapy, radiation, time to recurrence, and survival were recorded. Kaplan-Meier survival analyses and Cox proportional hazard models were completed to determine survival rates and prognostic factors. RESULTS Anaplastic histology/WHO Grade III tumors were identified in 62% of cases and correlated with older age. Three-, 5-, and 10-year PFS rates were 57%, 51%, and 42%, respectively. Three-, 5-, and 10-year OS rates were 77%, 71%, and 58%, respectively. EOR and tumor grade were identified on both Kaplan-Meier log-rank testing and univariate Cox proportional hazard models as prognostic for PFS and OS. Both EOR and tumor grade remained prognostic on multivariate analysis. Subtotal resection (STR) predicted a worse PFS (hazard ratio [HR] 4.764, p = 0.001) and OS (HR 4.216, p = 0.008). Subgroup survival analysis of patients with STR demonstrated a 5- and 10-year OS of 28% and 0%, respectively. WHO Grade III tumors also had worse PFS (HR 10.2, p = 0.004) and OS (HR 9.1, p = 0.035). Patients with WHO Grade III tumors demonstrated 5- and 10-year OS of 61% and 46%, respectively. Postoperative radiation was not prognostic for PFS or OS. CONCLUSIONS A high incidence of anaplastic histology was found in hemispheric ependymomas and was associated with older age. EOR and tumor grade were prognostic factors for PFS and OS on multivariate analysis. STR or WHO Grade III pathology, or both, predicted worse overall prognosis in patients

  1. Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

    PubMed Central

    2011-01-01

    Background Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival. Methods A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers. Results A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events. Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations. Biological processes

  2. Cognitive and affective assessment in day care versus institutionalized elderly patients: a 1-year longitudinal study

    PubMed Central

    Maseda, Ana; Balo, Aránzazu; Lorenzo–López, Laura; Lodeiro–Fernández, Leire; Rodríguez–Villamil, José Luis; Millán–Calenti, José Carlos

    2014-01-01

    Purpose Cognitive decline and depression are two common mental health problems that may create a need for long-term care among the elderly. In the last decade, the percentage of older adults who receive health care in nursing homes, day care centers, or home support services has increased in Europe. The objectives of this descriptive and nonrandomized longitudinal study were to evaluate and to compare the cognitive and affective evolution of day care versus institutionalized older patients through a 1-year period, and to assess the presence of cognitive and affective impairment as a function of the care setting. Patients and methods Ninety-four patients were assessed at baseline, and 63 (67.0%) were reassessed 1 year later. Neuropsychological assessment included measures of cognitive performance (general cognitive status, visuospatial, and language abilities) and affective status (depressive symptoms). Results Our findings indicated that the majority of the participants (day care and institutionalized patients) had mild–moderate cognitive impairment at baseline, which significantly increased in both groups after 1-year follow-up. However, the rate of change in global cognitive function did not significantly differ between groups over time. Regarding language abilities, naming function maintained among day care patients in comparison with institutionalized patients, who showed worse performance at follow-up. As regards to affective status, results revealed that institutionalized patients had a significant reduction in depressive symptoms at follow-up, when compared to day care patients. Results also highlight the high frequency of cognitive impairment and depressive symptoms regardless of the care setting. Conclusion Our findings revealed a similar global cognitive decline rate between patients receiving day care services and those residing in a nursing home at the 1-year follow-up, and slightly different trajectories in other outcomes such as naming function and

  3. Fathers' Depression Related to Positive and Negative Parenting Behaviors With 1-Year-Old Children

    PubMed Central

    Davis, Matthew M.; Freed, Gary L.; Clark, Sarah J.

    2011-01-01

    OBJECTIVE: To examine the associations between depression in fathers of 1-year-old children and specific positive and negative parenting behaviors discussed by pediatric providers at well-child visits. METHODS: We performed a cross-sectional secondary analysis by using interview data from 1746 fathers of 1-year-old children in the Fragile Families and Child Wellbeing Study. Positive parenting behaviors included fathers' reports of playing games, singing songs, and reading stories to their children ≥3 days in a typical week. Negative parenting behavior included fathers' reports of spanking their 1-year-old children in the previous month. Depression was assessed by using the World Health Organization Composite International Diagnostic Interview Short Form. Weighted bivariate and multivariate analyses of parenting behaviors were performed while controlling for demographics and paternal substance abuse. RESULTS: Overall, 7% of fathers had depression. In bivariate analyses, depressed fathers were more likely than nondepressed fathers to report spanking their 1-year-old children in the previous month (41% compared with 13%; P < .01). In multivariate analyses, depressed fathers were less likely to report reading to their children ≥3 days in a typical week (adjusted odds ratio: 0.38 [95% confidence interval: 0.15–0.98]) and much more likely to report spanking (adjusted odds ratio: 3.92 [95% confidence interval: 1.23–12.5]). Seventy-seven percent of depressed fathers reported talking to their children's doctor in the previous year. CONCLUSIONS: Paternal depression is associated with parenting behaviors relevant to well-child visits. Pediatric providers should consider screening fathers for depression, discussing specific parenting behaviors (eg, reading to children and appropriate discipline), and referring for treatment if appropriate. PMID:21402627

  4. A Simple Tool to Predict ESRD Within 1 Year in Elderly Patients with Advanced CKD

    PubMed Central

    Drawz, Paul E.; Goswami, Puja; Azem, Reem; Babineau, Denise C.; Rahman, Mahboob

    2013-01-01

    BACKGROUND/OBJECTIVES Chronic kidney disease (CKD) is common in older patients; currently, no tools are available to predict the risk of end-stage renal disease (ESRD) within 1 year. The goal of this study was to develop and validate a model to predict the 1 year risk for ESRD in elderly subjects with advanced CKD. DESIGN Retrospective study SETTING Veterans Affairs Medical Center PARTICIPANTS Patients over 65 years of age with CKD with an estimated (eGFR) less than 30mL/min/1.73m2. MEASUREMENTS The outcome was ESRD within 1 year of the index eGFR. Cox regression was used to develop a predictive model (VA risk score) which was validated in a separate cohort. RESULTS Of the 1,866 patients in the developmental cohort, 77 developed ESRD. Risk factors for ESRD in the final model were age, congestive heart failure, systolic blood pressure, eGFR, potassium, and albumin. In the validation cohort, the C index for the VA risk score was 0.823. The risk for developing ESRD at 1 year from lowest to highest tertile was 0.08%, 2.7%, and 11.3% (P<0.001). The C-index for the recently published Tangri model in the validation cohort was 0.780. CONCLUSION A new model using commonly available clinical measures shows excellent ability to predict the onset of ESRD within the next year in elderly subjects. Additionally, the Tangri model had very good predictive ability. Patients and physicians can use these risk models to inform decisions regarding preparation for renal replacement therapy in patients with advanced CKD. PMID:23617782

  5. Percutaneous coronary intervention in the elderly: procedural success and 1-year outcomes.

    PubMed

    Eckart, Robert E; Shry, Eric A; Simpson, Daniel E; Stajduhar, Karl C

    2003-01-01

    Clinical trials have found increased morbidity in elderly persons presenting for percutaneous coronary intervention for chronic stable angina. Long-term follow-up is limited for the elderly following percutaneous coronary intervention. The authors reviewed all coronary interventions performed from January 1998 to August 2001. One year following the procedure, subjects were screened for death, need for revascularization, and myocardial infarction. There were 401 subjects aged >/=65 years (mean 73.4+/-6.0 years) and 479 subjects aged <65 years (mean 55.6+/-6.7 years). Although there was no difference in 1-year rate of subsequent myocardial infarction or in revascularization, the elderly were more likely to die during hospitalization (4.7% vs. 1.0%, p<0.01), and at 1 year (10.2% vs. 4.0%, p<0.01). When controlled for ejection fraction, age was no longer significant in either predischarge mortality or in 1-year mortality. Excess postpercutaneous coronary intervention mortality in the elderly may be due to underlying comorbidities and not due to subsequent myocardial infarction or revascularization. PMID:14610387

  6. Infants under 1 year of age have a significant risk of burn injury.

    PubMed

    Nguyen, Dai Q A; Tobin, Sean; Dickson, William A; Potokar, Tom S

    2008-09-01

    A wealth of data exists concerning paediatric burn epidemiology in general, but very little exists specifically in infants under 1 year of age, a special group in which mobility begins to develop. A retrospective study of all burn admissions of infants under 1 year old to The Welsh Centre for Burns from January 2003 to January 2006 was performed. During the 3-year period there were 104 new burns cases identified which represents 11.8% of all paediatric admissions. 63.5% (66) were treated as inpatients and 36.5% (38) treated as out-patients. Burns increased in frequency with increasing age and occurred mainly in the home. Scalds were the commonest type of burn in 65% (68) whilst the second most common was contact burns which accounted for 30% (31). The most common source of scald was from cups containing hot drinks (39%) and the most common source of contact burn was radiators/hot water pipes (30%). The mean TBSA was 2.3%, (range 0.5-38%). The frequency of burns in the under 1 year old population highlights a need for emphasis of burn prevention directed to this group. Special attention is needed to look at the specific aetiology of these burns. Starting points for prevention should address the number of burns surrounding hot drinks and bottle warming practices in the case of scalds and the dangers of household radiators and hot water pipes in the case of contact burns. PMID:18378092

  7. Association of Postpartum Depression With Weight Retention 1 Year After Childbirth

    PubMed Central

    Herring, Sharon J.; Rich-Edwards, Janet W.; Oken, Emily; Rifas-Shiman, Sheryl L.; Kleinman, Ken P.; Gillman, Matthew W.

    2009-01-01

    Objective To examine the extent to which early postpartum depression is associated with weight retention 1 year after childbirth. Methods and Procedures In a prospective cohort study of 850 women enrolled in Project Viva, mothers reported depressive symptoms on the Edinburgh Postnatal Depression Scale (EPDS) at midpregnancy and 6 months postpartum. A score >12 indicated probable depression. We assessed associations of antenatal and postpartum depression with risk of substantial weight retention (at least 5 kg) 1 year after childbirth. Results Seven-hundred thirty-six women (87%) were not depressed during or after pregnancy, 55 (6%) experienced antenatal depression only, 22 (3%) experienced both antenatal and postpartum depression, and 37 (4%) experienced postpartum depression only. At 1 year, participants retained a mean of 0.6 kg (range −16.4 to 25.5), and 12% retained at least 5 kg. In multivariate logistic regression analyses, after adjustment for weight-related covariates, maternal sociodemographics, and parity, new-onset postpartum depression was associated with more than a doubling of risk of retaining at least 5 kg (odds ratio (OR): 2.54, 95% confidence interval (CI): 1.06, 6.09). Antenatal depression, either alone or in combination with postpartum depression, was not associated with substantial weight retention. Discussion New-onset postpartum depression was associated with substantial weight retention in the first postpartum year. Interventions to manage depressive symptoms may help reduce excess weight retained postpartum and aid in the prevention of obesity among women. PMID:18369338

  8. Survival of falling robots

    NASA Technical Reports Server (NTRS)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-01-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  9. Survival Skills: Secondary.

    ERIC Educational Resources Information Center

    Curriculum Review, 1979

    1979-01-01

    Reviewed are five programs (textbooks, audiovisual materials, workbooks, video-cassettes) designed to improve academic survival skills in secondary students. Content emphasis, reading level, rationale, objectives, organization, instructional method, student evaluation, physical features, and recommendations are listed for each. (KC)

  10. Survival at Isle Royale.

    ERIC Educational Resources Information Center

    Ballone, Lena M.

    2001-01-01

    Describes a simulation based on the popular television show "Survivor" in which students work in groups and study physiological needs for human survival. Focuses on communication skills, problem solving, and cooperative learning. (YDS)

  11. Survival of falling robots

    NASA Astrophysics Data System (ADS)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-02-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  12. Surviving at extremes

    NASA Astrophysics Data System (ADS)

    Dougan, Lorna

    2015-11-01

    Wherever we look on Earth - even in the most inhospitable places - we find life. But how do organisms manage to survive such difficult conditions? Lorna Dougan explains how physicists are helping to unravel the properties of “extremophile” life.

  13. Surviving Operation Desert Storm

    SciTech Connect

    Vice, J. )

    1992-08-01

    The importance of aircraft survivability during the invasion of Iraq is examined detailing anecdotal evidence of susceptibility and vulnerability reduction. Among the aircraft used that were designed to be more survivable than their predecessors were the F-117, A-10, F/A-18, and the AH-64. Reduced vulnerability is incorporated into the aircraft designs in the form of damage tolerant components, redundancy, self-sealing fluid systems, and miniaturization.

  14. Survival analysis of cancer patients with multiple endpoints using global score test methodology

    NASA Astrophysics Data System (ADS)

    Zain, Zakiyah; Whitehead, John

    2014-06-01

    Progression-free survival (PFS), time-to-progression (TTP) and overall survival (OS) are examples of multiple endpoints commonly used in clinical trials of cancer patients. PFS is increasingly used as a primary endpoint in evaluation of patients with solid tumors, while multiple endpoints are often analysed independently. These endpoints are indeed correlated and it is desirable to evaluate effectiveness of treatments by means of a single parameter. In this paper, a single overall treatment effect is provided by combining the univariate score statistics for comparing treatments with respect to each survival endpoint. This global score test methodology was applied in analysis of 330 patients with an aggressive cancer, each with two endpoints recorded, T1 and T2, relating to disease progression and death respectively. The values of score statistics obtained from the proposed method matched closely those from the logrank test. Meanwhile, the correlations between the two score test statistics were found to be similar to those computed using the established Wei, Lin and Weissfeld method. Simulations further confirmed the consistent performance of this new method in analysis of bivariate survival data.

  15. Mathematical Modeling of Therapy-induced Cancer Drug Resistance: Connecting Cancer Mechanisms to Population Survival Rates

    PubMed Central

    Sun, Xiaoqiang; Bao, Jiguang; Shao, Yongzhao

    2016-01-01

    Drug resistance significantly limits the long-term effectiveness of targeted therapeutics for cancer patients. Recent experimental studies have demonstrated that cancer cell heterogeneity and microenvironment adaptations to targeted therapy play important roles in promoting the rapid acquisition of drug resistance and in increasing cancer metastasis. The systematic development of effective therapeutics to overcome drug resistance mechanisms poses a major challenge. In this study, we used a modeling approach to connect cellular mechanisms underlying cancer drug resistance to population-level patient survival. To predict progression-free survival in cancer patients with metastatic melanoma, we developed a set of stochastic differential equations to describe the dynamics of heterogeneous cell populations while taking into account micro-environment adaptations. Clinical data on survival and circulating tumor cell DNA (ctDNA) concentrations were used to confirm the effectiveness of our model. Moreover, our model predicted distinct patterns of dose-dependent synergy when evaluating a combination of BRAF and MEK inhibitors versus a combination of BRAF and PI3K inhibitors. These predictions were consistent with the findings in previously reported studies. The impact of the drug metabolism rate on patient survival was also discussed. The proposed model might facilitate the quantitative evaluation and optimization of combination therapeutics and cancer clinical trial design. PMID:26928089

  16. Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma.

    PubMed

    Yamashita, Hideomi; Onishi, Hiroshi; Murakami, Naoya; Matsumoto, Yasuo; Matsuo, Yukinori; Nomiya, Takuma; Nakagawa, Keiichi

    2015-05-01

    Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated. A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child-Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy. The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II-III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed. PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation. PMID:25691453

  17. Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma

    PubMed Central

    Yamashita, Hideomi; Onishi, Hiroshi; Murakami, Naoya; Matsumoto, Yasuo; Matsuo, Yukinori; Nomiya, Takuma; Nakagawa, Keiichi

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated. A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child–Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy. The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II–III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed. PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation. PMID:25691453

  18. Mathematical Modeling of Therapy-induced Cancer Drug Resistance: Connecting Cancer Mechanisms to Population Survival Rates.

    PubMed

    Sun, Xiaoqiang; Bao, Jiguang; Shao, Yongzhao

    2016-01-01

    Drug resistance significantly limits the long-term effectiveness of targeted therapeutics for cancer patients. Recent experimental studies have demonstrated that cancer cell heterogeneity and microenvironment adaptations to targeted therapy play important roles in promoting the rapid acquisition of drug resistance and in increasing cancer metastasis. The systematic development of effective therapeutics to overcome drug resistance mechanisms poses a major challenge. In this study, we used a modeling approach to connect cellular mechanisms underlying cancer drug resistance to population-level patient survival. To predict progression-free survival in cancer patients with metastatic melanoma, we developed a set of stochastic differential equations to describe the dynamics of heterogeneous cell populations while taking into account micro-environment adaptations. Clinical data on survival and circulating tumor cell DNA (ctDNA) concentrations were used to confirm the effectiveness of our model. Moreover, our model predicted distinct patterns of dose-dependent synergy when evaluating a combination of BRAF and MEK inhibitors versus a combination of BRAF and PI3K inhibitors. These predictions were consistent with the findings in previously reported studies. The impact of the drug metabolism rate on patient survival was also discussed. The proposed model might facilitate the quantitative evaluation and optimization of combination therapeutics and cancer clinical trial design. PMID:26928089

  19. Total peroxiredoxin expression is associated with survival in patients with follicular lymphoma.

    PubMed

    Peroja, Pekka; Haapasaari, Kirsi-Maria; Mannisto, Susanna; Miinalainen, Ilkka; Koivunen, Petri; Leppä, Sirpa; Karjalainen-Lindsberg, Marja-Liisa; Kuusisto, Milla Elvi Linnea; Turpeenniemi-Hujanen, Taina; Kuittinen, Outi; Karihtala, Peeter

    2016-05-01

    Redox state-regulating enzymes may have roles in chemoresistance and also in lymphomagenesis, but there have been only a limited number of studies on this topic in lymphomas. Our aim was to assess expression of the redox state-regulating enzymes peroxiredoxins (Prxs) I-VI and thioredoxin (Trx) and the oxidative stress marker nitrotyrosine in follicular lymphomas (FLs). We immunohistochemically assessed Prxs I-VI, Trx and nitrotyrosine in a cohort of 76 histologically confirmed, untreated FLs. We also studied the localisation of Prxs I, II, III, V and VI by means of immunoelectron microscopy (IEM). Immunohistochemistry results were correlated with disease-specific survival (DSS), progression-free survival (PFS), overall survival (OS) and clinical prognostic factors. When all Prx expression intensities were grouped as a single variable, we discovered that high total Prx intensity correlated with favourable DSS (p = 0.024) and OS (p = 0.035) but not with PFS. No deaths due to lymphoma were recorded amongst patients with high total Prx expression during the median follow-up period of 7.6 years. IEM results were in line with earlier ones demonstrating wide subcellular localisation of Prx isoenzymes. In conclusion, our results demonstrate an association between high total Prx expression and prolonged survival and suggest that Prxs may have a protective role in FL that cannot be compensated by other antioxidant mechanisms. PMID:26983700

  20. Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial

    PubMed Central

    Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

    2015-01-01

    The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival. PMID:26219568

  1. Survival Rates for Thymus Cancer

    MedlinePlus

    ... staged? Next Topic How is thymus cancer treated? Survival rates for thymus cancer Survival rates are often ... into account. Stage of thymoma 5-year observed survival rate I 74% II 73% III 64% IV ...

  2. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone.

    PubMed

    Dimopoulos, Meletios A; Weisel, Katja C; Song, Kevin W; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Spencer, Andrew; Knop, Stefan; Bahlis, Nizar J; Renner, Christoph; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H; San Miguel, Jesus F

    2015-10-01

    Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P <0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or high-dose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del(17p) (31.8% versus 4.3%), whereas it was similar in patients with t(4;14) (15.9% versus 13.3%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma

  3. The value of pre-operative multicompartment pelvic floor ultrasonography: a 1-year prospective study

    PubMed Central

    Lone, F; Stankiewicz, A; Thakar, R

    2014-01-01

    Objective: Comprehensive assessment of the pelvic floor (PF) provides information and diagnoses of coexisting abnormalities that may affect operative decisions. Our aim was to establish if pre-operative PF ultrasonography (PFUS) in patients complaining of PF dysfunction can complement clinical findings and contribute to additional management strategies. Methods: Females were recruited from the urogynaecology/gynaecology clinics between July and October 2009 and underwent pelvic organ prolapse quantification (POPQ) by an independent examiner. PFUS was performed using two-dimensional (2D) transperineal ultrasound (TPUS), high-frequency 2D/three-dimensional (3D) endovaginal ultrasound (EVUS) using a biplane probe with linear and transverse arrays and a 360° rotational 3D-EVUS. The clinician performing PFUS was blinded to POPQ results. POPQ and PFUS were repeated at 1 year. Two clinicians analysed the scans independently. Results: 158 of 160 females had a POPQ and PFUS. 105 females had pelvic organ prolapse and/or incontinence and 53 asymptomatic females were controls. 26 additional ultrasound diagnoses were noted at baseline and 46 at 1 year using 2D-TPUS and EVUS. Only one female with additional diagnoses on PFUS needed surgical intervention for this condition. Conclusion: Multicompartment PFUS identifies additional conditions to that diagnosed on clinical assessment. However, it neither changes the initial surgical management nor the management at 1-year follow-up and therefore clinical assessment should not be substituted by PFUS. Advances in knowledge: PFUS can be helpful in providing additional information; however, it does not change the initial management of the patient and therefore should not replace clinical assessment. PMID:24959953

  4. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    SciTech Connect

    Du, Zhongli; Zhang, Wencheng; Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen; Xiao, Zefen; Tan, Wen; and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  5. Brucella arthritis of the knee, 1 year after revision of anterior cruciate ligament reconstruction.

    PubMed

    Papastergiou, S G; Koukoulias, N E; Koumis, P; Kyparlis, D; Santas, R

    2011-01-01

    Brucellosis is a zoonotic infection with a broad spectrum of clinical manifestations. The authors report the first case in the literature of septic arthritis of the knee 1 year after revision of anterior cruciate ligament reconstruction. Brucella melitensis biotype 3 was found in both synovial fluid and blood cultures. The patient was treated initially with arthroscopic debridement. After the diagnosis was confirmed, a second arthroscopic lavage and metal work removal was applied leaving the graft in place. Antimicrobial chemotherapy was prescribed for 3 months. The infection was fully eradicated and the patient is still asymptomatic, 4 years after the treatment. PMID:22700607

  6. Brucella arthritis of the knee, 1 year after revision of anterior cruciate ligament reconstruction

    PubMed Central

    Papastergiou, S G; Koukoulias, N E; Koumis, P; Kyparlis, D; Santas, R

    2011-01-01

    Brucellosis is a zoonotic infection with a broad spectrum of clinical manifestations. The authors report the first case in the literature of septic arthritis of the knee 1 year after revision of anterior cruciate ligament reconstruction. Brucella melitensis biotype 3 was found in both synovial fluid and blood cultures. The patient was treated initially with arthroscopic debridement. After the diagnosis was confirmed, a second arthroscopic lavage and metal work removal was applied leaving the graft in place. Antimicrobial chemotherapy was prescribed for 3 months. The infection was fully eradicated and the patient is still asymptomatic, 4 years after the treatment. PMID:22700607

  7. Traumatic spinal epidural hematoma in a 1-year-old boy.

    PubMed

    Tarbé de Saint Hardouin, A-L; Grévent, D; Sainte-Rose, C; Angoulvant, F; Chéron, G

    2016-07-01

    Traumatic spinal epidural hematoma is uncommon in children, making rapid diagnosis difficult. In this report, we present a case of traumatic cervical epidural hematoma in a 1-year-old boy, diagnosed with computed tomography scanning and magnetic resonance imaging (MRI). Management was conservative and the lesion regressed spontaneously. The presentation in childhood is often nonspecific. MRI is the imaging modality of choice for diagnosing these lesions. Conservative treatment has to be considered in cases with a benign clinical course and provided that the patient is followed up neurologically with repeated MRI. PMID:27266638

  8. Necessity and Opportunity: the 1-Year Master's ABA Program at Auburn University.

    PubMed

    Johnston, James M

    2016-05-01

    The Auburn University Master of Science program in Applied Behavior Analysis was designed to accommodate not only the requirements of the Behavior Analyst Certification Board for approved course sequences and practicum training, but unavoidable limitations in faculty and other resources. These limitations were incompatible with the more traditional 2-year curriculum model, so a 1-year program was designed that met the necessary conditions. This article describes the resulting academic and practicum curriculum, the key funding mechanisms that allowed the program to develop, and the opportunities and benefits that this model afforded. PMID:27606193

  9. Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

    SciTech Connect

    Gielda, Benjamin T.; Mehta, Par; Khan, Atif; Marsh, James C.; Zusag, Thomas W.; Warren, William H.; Fidler, Mary Jo; Abrams, Ross A.; Bonomi, Philip; Liptay, Michael; Faber, L. Penfield

    2011-11-15

    Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

  10. Comparison of long-term survival between temozolomide-based chemoradiotherapy and radiotherapy alone for patients with low-grade gliomas after surgical resection

    PubMed Central

    Gai, Xiu-juan; Wei, Yu-mei; Tao, Heng-min; An, Dian-zheng; Sun, Jia-teng; Li, Bao-sheng

    2016-01-01

    Purpose This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT) vs radiotherapy alone (RT-alone) for low-grade gliomas (LGGs) after surgical resection. Patients and methods In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31) and RT-alone (n=38) at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50–100 mg oral TMZ every day until the radiotherapy regimen was completed. Results The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06). There were statistically significant intergroup differences in the progression-free survival rate (P=0.037), with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS) rate was 89.86%. Age distribution (≥45 years and <45 years) and resection margin (complete resection or not) were significantly associated with OS (P=0.03 and P=0.004, respectively). Conclusion Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between prognostic factors and long-term survival may be worthy of further investigation. PMID:27574452

  11. Induction of Maturogenesis by Partial Pulpotomy: 1 Year Follow-Up

    PubMed Central

    Bacaksiz, A.; Alaçam, A.

    2013-01-01

    In cariously exposed immature permanent teeth, the treatment choice is controversial in pediatric dentistry. Radical root canal treatment usually appears to be the solution for these teeth. Even partial pulpotomy is a vital treatment for traumatically exposed immature permanent teeth; extending the borders of indication towards cariously exposed immature permanent teeth with reversible pulpitis may abolish the necessity of pulpectomy. This article describes the partial pulpotomy of a cariously affected immature permanent teeth and the follow-up for 1 year. A healthy 11-year-old male patient was referred to Gazi University Faculty of Dentistry Department of Pediatric Dentistry. The patient had reversible pulpitis symptoms on teeth numbered 45. At radiographic examination, immature apex and deep caries lesion were observed and partial pulpotomy was performed by using calcium hydroxide to maintain vitality of the pulp and allow continued development of root dentin expecting the root will attain full maturity. Clinical and radiographic follow-up demonstrated a vital pulp besides not only closure of the apex (apexogenesis), but also physiologic root development (maturogenesis) after 1 year. Partial pulpotomy is an optional treatment for cariously exposed immature permanent teeth for preserving vitality and physiological root development. PMID:24324899

  12. Safety and efficacy of nurse-controlled analgesia in patients less than 1 year of age

    PubMed Central

    Walia, Hina; Tumin, Dmitry; Wrona, Sharon; Martin, David; Bhalla, Tarun; Tobias, Joseph D

    2016-01-01

    Background The management of acute pain presents unique challenges in the younger pediatric population. Although patient-controlled devices are frequently used in patients ≥6 years of age, alternative modes of analgesic delivery are needed in infants. Objective To examine the safety and efficacy of nurse-controlled analgesia (NCA) in neonates less than 1 year of age. Methods Data from patients <1 year of age receiving NCA as ordered by the Acute Pain Service at our institution were collected over a 5-year period and reviewed retrospectively. The primary outcomes were activation of the institution’s Rapid Response Team (RRT) or Code Blue, signifying severe adverse events. Pain score after NCA initiation was a secondary outcome. Results Among 338 girls and 431 boys, the most common opioid used for NCA was fentanyl, followed by morphine and hydromorphone. There were 39 (5%) cases involving RRT or Code Blue activation, of which only one (Code Blue) was activated due to a complication of NCA (apnea). Multivariable logistic regression demonstrated morphine NCA to be associated with greater odds of RRT activation (OR=3.29, 95% CI=1.35, 8.03, P=0.009) compared to fentanyl NCA. There were no statistically significant differences in pain scores after NCA initiation across NCA agents. Conclusion NCA is safe in neonates and infants, with comparable efficacy demonstrated for the three agents used. The elevated incidence of RRT activation in patients receiving morphine suggests caution in its use and consideration of alternative agents in this population.

  13. Parental spanking of 1-year-old children and subsequent child protective services involvement✩

    PubMed Central

    Lee, Shawna J.; Grogan-Kaylor, Andrew; Berger, Lawrence M.

    2015-01-01

    The majority of U.S. parents spank their children, often beginning when their children are very young. We examined families (N=2,788) who participated in a longitudinal community-based study of new births in urban areas. Prospective analyses examined whether spanking by the child's mother, father, or mother's current partner when the child was 1-year-old was associated with household CPS involvement between age 1 and age 5. Results indicated that 30% of 1-year-olds were spanked at least once in the past month. Spanking at age 1 was associated with increased odds of subsequent CPS involvement (adjusted odds ratio=1.36, 95% CI [1.08, 1.71], p<.01). When compared to non-spanked children, there was a 33% greater probability of subsequent CPS involvement for children who were spanked at age 1. Given the undesirable consequences of spanking children and a lack of empirical evidence to suggest positive effects of physical punishment, professionals who work with families should counsel parents not to spank infants and toddlers. For optimal benefits, efforts to educate parents regarding alternative forms of discipline should begin during the child's first year of life. PMID:24602690

  14. Parental spanking of 1-year-old children and subsequent child protective services involvement.

    PubMed

    Lee, Shawna J; Grogan-Kaylor, Andrew; Berger, Lawrence M

    2014-05-01

    The majority of U.S. parents spank their children, often beginning when their children are very young. We examined families (N=2,788) who participated in a longitudinal community-based study of new births in urban areas. Prospective analyses examined whether spanking by the child's mother, father, or mother's current partner when the child was 1-year-old was associated with household CPS involvement between age 1 and age 5. Results indicated that 30% of 1-year-olds were spanked at least once in the past month. Spanking at age 1 was associated with increased odds of subsequent CPS involvement (adjusted odds ratio=1.36, 95% CI [1.08, 1.71], p<.01). When compared to non-spanked children, there was a 33% greater probability of subsequent CPS involvement for children who were spanked at age 1. Given the undesirable consequences of spanking children and a lack of empirical evidence to suggest positive effects of physical punishment, professionals who work with families should counsel parents not to spank infants and toddlers. For optimal benefits, efforts to educate parents regarding alternative forms of discipline should begin during the child's first year of life. PMID:24602690

  15. The Effect of Body Mass Index on Pelvic Floor Support 1 Year Postpartum.

    PubMed

    Chen, Yi; Johnson, Benjamin; Li, Fangyong; King, William C; Connell, Kathleen A; Guess, Marsha K

    2016-02-01

    Elevated body mass index (BMI) is associated with the incidence, prevalence, and progression of pelvic organ prolapse (POP). This study investigated the effect of peripartum BMI on pelvic floor support 1 year postpartum (PP1y). One hundred eight nulliparous women had their BMI recorded and underwent POP assessments using the Pelvic Organ Prolapse Quantification System at baseline, third trimester (36th to 38th week of pregnancy [G36-38w]), and PP1y. Pelvic organ prolapse was defined as ≥stage II. Women gained on average 1.9 kg between baseline and PP1y. After adjustment, increasing BMI PP1y was associated with increasing anterior wall descent (P < .0001) and higher odds of having POP PP1y (odds ratio: 1.41, 95% confidence interval: 1.01-1.97, P = .045). Trial of labor compared to unlabored cesarean delivery, POP G36-38w, and decreased fetal weight were independently associated with anterior vaginal wall laxity PP1y. Our finding suggests that postpartum BMI influences pelvic floor laxity 1 year after delivery. Postpartum weight reduction may serve as a strategy for POP prevention in some women. PMID:26494698

  16. BDNF mediates improvements in executive function following a 1-year exercise intervention.

    PubMed

    Leckie, Regina L; Oberlin, Lauren E; Voss, Michelle W; Prakash, Ruchika S; Szabo-Reed, Amanda; Chaddock-Heyman, Laura; Phillips, Siobhan M; Gothe, Neha P; Mailey, Emily; Vieira-Potter, Victoria J; Martin, Stephen A; Pence, Brandt D; Lin, Mingkuan; Parasuraman, Raja; Greenwood, Pamela M; Fryxell, Karl J; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F; Erickson, Kirk I

    2014-01-01

    Executive function declines with age, but engaging in aerobic exercise may attenuate decline. One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor (BDNF), which also declines with age. The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults (mean age = 66.82). Participants were randomized to a stretching and toning control group or a moderate intensity walking intervention group. BDNF serum levels and performance on a task-switching paradigm were collected at baseline and follow-up. We found that age moderated the effect of intervention group on changes in BDNF levels, with those in the highest age quartile showing the greatest increase in BDNF after 1-year of moderate intensity walking exercise (p = 0.036). The mediation analyses revealed that BDNF mediated the effect of the intervention on task-switch accuracy, but did so as a function of age, such that exercise-induced changes in BDNF mediated the effect of exercise on task-switch performance only for individuals over the age of 71. These results demonstrate that both age and BDNF serum levels are important factors to consider when investigating the mechanisms by which exercise interventions influence cognitive outcomes, particularly in elderly populations. PMID:25566019

  17. Determinants of telomere attrition over 1 year in healthy older women: stress and health behaviors matter.

    PubMed

    Puterman, E; Lin, J; Krauss, J; Blackburn, E H; Epel, E S

    2015-04-01

    Telomere length, a reliable predictor of disease pathogenesis, can be affected by genetics, chronic stress and health behaviors. Cross-sectionally, highly stressed postmenopausal women have shorter telomeres, but only if they are inactive. However, no studies have prospectively examined telomere length change over a short period, and if rate of attrition is affected by naturalistic factors such as stress and engagement in healthy behaviors, including diet, exercise, and sleep. Here we followed healthy women over 1 year to test if major stressors that occurred over the year predicted telomere shortening, and whether engaging in healthy behaviors during this period mitigates this effect. In 239 postmenopausal, non-smoking, disease-free women, accumulation of major life stressors across a 1-year period predicted telomere attrition over the same period-for every major life stressor that occurred during the year, there was a significantly greater decline in telomere length over the year of 35 bp (P<0.05). Yet, these effects were moderated by health behaviors (interaction B=0.19, P=0.04). Women who maintained relatively higher levels of health behaviors (1 s.d. above the mean) appeared to be protected when exposed to stress. This finding has implications for understanding malleability of telomere length, as well as expectations for possible intervention effects. This is the first study to identify predictors of telomere length change over the short period of a year. PMID:25070535

  18. Residual skin damage in rats 1 year after exposure to x rays or accelerated heavy ions

    SciTech Connect

    Leith, J.T.; McDonald, M.; Howard, J.

    1982-01-01

    In conjunction with a study on the biological effects of accelerated heavy ions on rat spinal cord, we were able to assess the residual skin damage remaining 1 year postirradiation. In this study, rats were irradiated with 230-kVp fractionated doses of either X rays, carbon ions, or neon ions. Four radiation fractions were given at daily intervals. For the carbon and neon ion exposures, rats were irradiated in both the plateau and spread Bragg peak (4 cm) regions of ionization. Comparing doses that produced complete epilation with a slight suggestion of a residual radiation scar, it was found that the relative biological effectivesness (RBE) values 1 year postirradiation for the four fraction irradiations were: carbon ions (plateau ionization region), 1.06; carbon ions (spread Bragg peak ionization region), 1.88; neon ions (plateau region of ionization), 1.55; and neon ions (spread Bragg peak ionization region), 2.26. RBE values for production of paralysis after spinal cord irradiation (using the same X-ray total dose levels for comparison purposes) were in all cases higher than the RBE values obtained from assessment of residual skin injury.

  19. Enhancing Coparenting, Parenting, and Child Self-Regulation: Effects of Family Foundations 1 Year after Birth

    PubMed Central

    Feinberg, Mark E.; Kan, Marni L.; Goslin, Megan C.

    2011-01-01

    This study investigated whether a psycho-educational program with modest dosage (eight sessions), delivered in a universal framework through childbirth education programs and targeting the coparenting relationship would have a positive impact on observed family interaction and child behavior at 6-month follow-up (child age 1 year). One hundred sixty-nine couples, randomized to intervention and control conditions, participated in videotaped family observation tasks at pretest (during pregnancy) and at child age 1 year (2003–2007). Coparenting, parenting, couple relationship, and child self-regulatory behaviors were coded by teams of raters. Intent-to-treat analyses of program effects controlled for age, education, and social desirability. Evidence of significant (p<0.05) program effects at follow-up emerged in all four domains. Effect sizes ranged from 0.28 to 1.01. Targeting the coparenting relationship at the transition to parenthood represents an effective, non-stigmatizing means of promoting parenting quality and child adjustment. PMID:19381809

  20. Phase Fluctuations at Goldstone Derived from 1-Year Site Testing Interferometer Data

    NASA Technical Reports Server (NTRS)

    Nessel, James A.; Acosta, Roberto J.; Morabito, David D.

    2009-01-01

    A two-element site test interferometer has been deployed at the NASA Deep Space Network (DSN) tracking complex in Goldstone, California, since May 2007. The interferometer system consists of two offset-fed 1.2 m parabolic reflectors which monitor atmospheric-induced amplitude and phase fluctuations on an unmodulated beacon signal (20.199 GHz) broadcast from a geostationary satellite (Anik F2). The geometry of the satellite and the ground-based infrastructure imposes a 48.5 elevation angle with a separation distance of 256 m along an east-west baseline. The interferometer has been recording phase fluctuation data, to date, for 1 yr with an overall system availability of 95 percent. In this paper, we provide the cumulative distribution functions (CDFs) for 1 year of recorded data, including phase rms, spatial structure function exponent, and surface meteorological measurements: surface wind speed, relative humidity, temperature, barometric pressure, and rain rate. Correlation between surface measurements, phase rms, and amplitude rms at different time scales are discussed. For 1 year, phase fluctuations at the DSN site in Goldstone, are better than 23 for 90 percent of the time (at 48.5 elevation). This data will be used to determine the suitability of the Goldstone site as a location for the Next Generation Deep Space Network.

  1. Surviving atmospheric spacecraft breakup

    NASA Technical Reports Server (NTRS)

    Szewczyk, Nathaniel J.; McLamb, William

    2005-01-01

    Spacecraft travel higher and faster than aircraft, making breakup potentially less survivable. As with aircraft breakup, the dissipation of lethal forces via spacecraft breakup around an organism is likely to greatly increase the odds of survival. By employing a knowledge of space and aviation physiology, comparative physiology, and search-and-rescue techniques, we were able to correctly predict and execute the recovery of live animals following the breakup of the space shuttle Columbia. In this study, we make what is, to our knowledge, the first report of an animal, Caenorhabditis elegans, surviving the atmospheric breakup of the spacecraft that was supporting it and discuss both the lethal events these animals had to escape and the implications for search and rescue following spacecraft breakup.

  2. Genetic Introgression and the Survival of Florida Panther Kittens

    PubMed Central

    Hostetler, Jeffrey A.; Onorato, David P.; Nichols, James D.; Johnson, Warren E.; Roelke, Melody E.; O’Brien, Stephen J.; Jansen, Deborah; Oli, Madan K.

    2010-01-01

    Estimates of survival for the young of a species are critical for population models. These models can often be improved by determining the effects of management actions and population abundance on this demographic parameter. We used multiple sources of data collected during 1982-2008 and a live recapture-dead recovery modeling framework to estimate and model survival of Florida panther (Puma concolor coryi) kittens (age 0 – 1 year). Overall, annual survival of Florida panther kittens was 0.323 ± 0.071 (SE), which was lower than estimates used in previous population models. In 1995, female pumas from Texas (P. c. stanleyana) were released into occupied panther range as part of an intentional introgression program to restore genetic variability. We found that kitten survival generally increased with degree of admixture: F1 admixed and backcrossed to Texas kittens survived better than canonical Florida panther and backcrossed to canonical kittens. Average heterozygosity positively influenced kitten and older panther survival, whereas index of panther abundance negatively influenced kitten survival. Our results provide strong evidence for the positive population-level impact of genetic introgression on Florida panthers. Our approach to integrate data from multiple sources was effective at improving robustness as well as precision of estimates of Florida panther kitten survival, and can be useful in estimating vital rates for other elusive species with sparse data. PMID:21113436

  3. Genetic Introgression and the Survival of Florida Panther Kittens.

    PubMed

    Hostetler, Jeffrey A; Onorato, David P; Nichols, James D; Johnson, Warren E; Roelke, Melody E; O'Brien, Stephen J; Jansen, Deborah; Oli, Madan K

    2010-11-01

    Estimates of survival for the young of a species are critical for population models. These models can often be improved by determining the effects of management actions and population abundance on this demographic parameter. We used multiple sources of data collected during 1982-2008 and a live recapture-dead recovery modeling framework to estimate and model survival of Florida panther (Puma concolor coryi) kittens (age 0 - 1 year). Overall, annual survival of Florida panther kittens was 0.323 ± 0.071 (SE), which was lower than estimates used in previous population models. In 1995, female pumas from Texas (P. c. stanleyana) were released into occupied panther range as part of an intentional introgression program to restore genetic variability. We found that kitten survival generally increased with degree of admixture: F(1) admixed and backcrossed to Texas kittens survived better than canonical Florida panther and backcrossed to canonical kittens. Average heterozygosity positively influenced kitten and older panther survival, whereas index of panther abundance negatively influenced kitten survival. Our results provide strong evidence for the positive population-level impact of genetic introgression on Florida panthers. Our approach to integrate data from multiple sources was effective at improving robustness as well as precision of estimates of Florida panther kitten survival, and can be useful in estimating vital rates for other elusive species with sparse data. PMID:21113436

  4. Genetic introgression and the survival of Florida panther kittens

    USGS Publications Warehouse

    Hostetler, Jeffrey A.; Onorato, David P.; Nichols, James D.; Johnson, Warren E.; Roelke, Melody E.; O'Brien, Stephen J.; Jansen, Deborah; Oli, Madan K.

    2010-01-01

    Estimates of survival for the young of a species are critical for population models. These models can often be improved by determining the effects of management actions and population abundance on this demographic parameter. We used multiple sources of data collected during 1982-2008 and a live-recapture dead-recovery modeling framework to estimate and model survival of Florida panther (Puma concolor coryi) kittens (age 0-1 year). Overall, annual survival of Florida panther kittens was 0.323 + or - 0.071 (SE), which was lower than estimates used in previous population models. In 1995, female pumas from Texas (P. c. stanleyana) were released into occupied panther range as part of an intentional introgression program to restore genetic variability. We found that kitten survival generally increased with degree of admixture: F1 admixed and backcrossed to Texas kittens survived better than canonical Florida panther and backcrossed to canonical kittens. Average heterozygosity positively influenced kitten and older panther survival, whereas index of panther abundance negatively influenced kitten survival. Our results provide strong evidence for the positive population-level impact of genetic introgression on Florida panthers. Our approach to integrate data from multiple sources was effective at improving robustness as well as precision of estimates of Florida panther kitten survival, and can be useful in estimating vital rates for other elusive species with sparse data.

  5. External validation of the Hospital-patient One-year Mortality Risk (HOMR) model for predicting death within 1 year after hospital admission

    PubMed Central

    van Walraven, Carl; McAlister, Finlay A.; Bakal, Jeffrey A.; Hawken, Steven; Donzé, Jacques

    2015-01-01

    Background: Predicting long-term survival after admission to hospital is helpful for clinical, administrative and research purposes. The Hospital-patient One-year Mortality Risk (HOMR) model was derived and internally validated to predict the risk of death within 1 year after admission. We conducted an external validation of the model in a large multicentre study. Methods: We used administrative data for all nonpsychiatric admissions of adult patients to hospitals in the provinces of Ontario (2003–2010) and Alberta (2011–2012), and to the Brigham and Women’s Hospital in Boston (2010–2012) to calculate each patient’s HOMR score at admission. The HOMR score is based on a set of parameters that captures patient demographics, health burden and severity of acute illness. We determined patient status (alive or dead) 1 year after admission using population-based registries. Results: The 3 validation cohorts (n = 2 862 996 in Ontario, 210 595 in Alberta and 66 683 in Boston) were distinct from each other and from the derivation cohort. The overall risk of death within 1 year after admission was 8.7% (95% confidence interval [CI] 8.7% to 8.8%). The HOMR score was strongly and significantly associated with risk of death in all populations and was highly discriminative, with a C statistic ranging from 0.89 (95% CI 0.87 to 0.91) to 0.92 (95% CI 0.91 to 0.92). Observed and expected outcome risks were similar (median absolute difference in percent dying in 1 yr 0.3%, interquartile range 0.05%–2.5%). Interpretation: The HOMR score, calculated using routinely collected administrative data, accurately predicted the risk of death among adult patients within 1 year after admission to hospital for nonpsychiatric indications. Similar performance was seen when the score was used in geographically and temporally diverse populations. The HOMR model can be used for risk adjustment in analyses of health administrative data to predict long-term survival among hospital patients

  6. Survival after judicial hanging.

    PubMed

    Sabermoghaddam, Mohsen; Abad, Mohsen; Golmakani, Ebrahim; Mozaffari, Nasrollah

    2015-06-01

    Hanging is known not only as a common method of suicide but also as a capital punishment method in some countries. Although several cases have been reported to survive after the attempted suicidal/accidental hanging, to the extent of our knowledge, no modern case of survival after judicial hanging exists. We reported a case of an individual who revived after modern judicial hanging despite being declared dead. The case was admitted with poor clinical presentations and the Glasgow Coma Scale of 6/15. The victim received all the standard supportive intensive care and gained complete clinical recovery. PMID:25747958

  7. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    SciTech Connect

    Wasserman, Todd H. . E-mail: twasserman@bellsouth.net; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

    2005-11-15

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m{sup 2} i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade {>=}2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival.

  8. The Option for Survival

    ERIC Educational Resources Information Center

    Berry, R. Stephen

    1971-01-01

    Suggests formula for survival that takes a thermodynamic view which holds that we must recycle waste while the thermodynamic potential still is moderately high. Otherwise they are lost, as helium is lost when it leaves Earth's atmosphere and goes into space. The idea that the Earth is a closed system is a myth; it collapses each time we put our…

  9. Independence and Survival.

    ERIC Educational Resources Information Center

    James, H. Thomas

    Independent schools that are of viable size, well managed, and strategically located to meet competition will survive and prosper past the current financial crisis. We live in a complex technological society with insatiable demands for knowledgeable people to keep it running. The future will be marked by the orderly selection of qualified people,…

  10. A Profile of Survival.

    ERIC Educational Resources Information Center

    Zimrin, Hanita

    1986-01-01

    Abused children who survived the trauma of their childhood and grew up to be well-adjusted were compared with a matched group who showed a high degree of psychosocial pathology. The variables which distinguished the two groups were fatalism, self-esteem, cognitive abilities, self-destructiveness, hope and fantasy, behavior patterns and external…

  11. Survivability via Control Objectives

    SciTech Connect

    CAMPBELL,PHILIP L.

    2000-08-11

    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  12. Education for Survival.

    ERIC Educational Resources Information Center

    Allen, James E., Jr.

    In this address, James E. Allen, Jr., Assistant Secretary for Education and U.S. Commissioner of Education, discusses the relationship of education to the problem of ecological destruction. He states that the solutions to the problems of air, water, and soil pollution may be found in redirected education. This "education for survival" can serve to…

  13. Survival Learning Materials.

    ERIC Educational Resources Information Center

    Wilson, Robert M.; Barnes, Marcia M.

    This booklet is designed to provide some starter ideas for teachers to use in developing their own packet of learning materials. The procedures suggested and the examples included are literally starters. "Introduction to Survival Learning Materials" presents some procedures to help teachers get started in developing materials. "Following…

  14. Substance use disorder counselors' job performance and turnover after 1 year: linear or curvilinear relationship?

    PubMed

    Laschober, Tanja C; de Tormes Eby, Lillian Turner

    2013-07-01

    The main goals of the current study were to investigate whether there are linear or curvilinear relationships between substance use disorder counselors' job performance and actual turnover after 1 year utilizing four indicators of job performance and three turnover statuses (voluntary, involuntary, and no turnover as the reference group). Using longitudinal data from 440 matched counselor-clinical supervisor dyads, results indicate that overall, counselors with lower job performance are more likely to turn over voluntarily and involuntarily than not to turn over. Further, one of the job performance measures shows a significant curvilinear effect. We conclude that the negative consequences often assumed to be "caused" by counselor turnover may be overstated because those who leave both voluntarily and involuntarily demonstrate generally lower performance than those who remain employed at their treatment program. PMID:22527711

  15. Predicting abuse in adolescent dating relationships over 1 year: the role of child maltreatment and trauma.

    PubMed

    Wolfe, David A; Wekerle, Christine; Scott, Katreena; Straatman, Anna-Lee; Grasley, Carolyn

    2004-08-01

    Three mediators of the relationship between childhood maltreatment and dating violence perpetration during midadolescence (i.e., trauma-related symptoms, attitudes justifying dating violence, and empathy and self-efficacy in dating relationships) were tested over 1 year with a sample of students from 10 high schools (N = 1,317). Trauma-related symptoms had a significant cross-time effect on predicting incidents of dating violence for both boys and girls. Attitudes and empathy and self-efficacy did not predict dating violence over time, although they were correlated with such behavior at both time points. Child maltreatment is a distal risk factor for adolescent dating violence, and trauma-related symptoms act as a significant mediator of this relationship. The importance of longitudinal methodology that separates correlates from predictors is discussed. PMID:15311986

  16. Whooping cough in South-East Romania: a 1-year study.

    PubMed

    Dinu, Sorin; Guillot, Sophie; Dragomirescu, Cristiana Cerasella; Brun, Delphine; Lazăr, Stefan; Vancea, Geta; Ionescu, Biatrice Mariana; Gherman, Mariana Felicia; Bjerkestrand, Andreea-Florina-Dana; Ungureanu, Vasilica; Guiso, Nicole; Damian, Maria

    2014-03-01

    The incidence of whooping cough in Romania is substantially underestimated, and, as noted by the health authorities, this is mostly due to the lack of both awareness and biological diagnosis. We conducted a 1-year study in Bucharest in order to assess the circulation of Bordetella pertussis, the main etiological agent of whooping cough. Fifty-one subjects suspected of whooping cough were enrolled. Culture, real-time PCR, and enzyme-linked immunosorbent assay were used for laboratory diagnosis. Whooping cough patients (63%) were distributed among all age groups, and most were unvaccinated, incompletely vaccinated, or had been vaccinated more than 5 years previously. Bordetella holmesii DNA was detected in 22% of the bordetellosis cases; these patients included adults; teenagers; and, surprisingly, young children. B. pertussis isolates were similar to the clinical isolates currently circulating elsewhere in Europe. One isolate does not express pertactin, an antigen included in some acellular pertussis vaccines. PMID:24355701

  17. Cognitive dysfunction at baseline predicts symptomatic 1-year outcome in first-episode schizophrenics.

    PubMed

    Moritz, S; Krausz, M; Gottwalz, E; Lambert, M; Perro, C; Ganzer, S; Naber, D

    2000-01-01

    The present study addresses the consequences of cognitive disturbances on symptomatic outcome. Fifty-three first-episode schizophrenics were reassessed (n = 32) 1 year after admission. Simple regression analyses revealed that several self-perceived cognitive deficits at baseline as measured with the Frankfurt Complaint Questionnaire significantly predicted increased Brief Psychiatric Rating Scale global scores at follow-up (p = 0.05 to p = 0.005). A stepwise regression analysis proved memory dysfunction to be the strongest predictor of symptomatic worsening (p = 0.005). It is suggested that the exploration and treatment of neuropsychological deficits in schizophrenia is of great clinical importance with regard to its impact on both functional and symptomatic outcome in schizophrenia. PMID:10601828

  18. [Interferon beta 1-a in multiple sclerosis: 1-year experience in 62 patients].

    PubMed

    Tilbery, C P; Felipe, E; Moreira, M A; Mendes, M F; França, A S

    2000-06-01

    We report the results of a trial of interferon beta 1-a in 62 ambulatory patients with relapsing-remitting multiple sclerosis. Entry criteria included EDSS of 0 to 5.5 and at least two exacerbations in the previous 2 years. The patients received 3 million international units by subcutaneous injections three times a week. The end points were differences in exacerbation rate and treatment effect on disease progression. The annual exacerbation rate for patients that did not take the interferon beta 1-a was 1.32 and for the patients under medication 0.63. The EDSS score in patients that did not take the mediaction was 4.7 and 2.0 for the patients with interferon beta 1-a. Interferon beta 1-a was well tolerated and 85% of patients completed 1 year treatment. PMID:10920406

  19. Substance Use Disorder Counselors’ Job Performance and Turnover after 1 Year: Linear or Curvilinear Relationship?1

    PubMed Central

    Laschober, Tanja C.; de Tormes Eby, Lillian Turner

    2013-01-01

    The main goals of the current study were to investigate whether there are linear or curvilinear relationships between substance use disorder counselors’ job performance and actual turnover after 1 year utilizing four indicators of job performance and three turnover statuses (voluntary, involuntary, and no turnover as the reference group). Using longitudinal data from 440 matched counselor-clinical supervisor dyads, results indicate that overall, counselors with lower job performance are more likely to turn over voluntarily and involuntarily than not to turn over. Further, one of the job performance measures shows a significant curvilinear effect. We conclude that the negative consequences often assumed to be “caused” by counselor turnover may be overstated because those who leave both voluntarily and involuntarily demonstrate generally lower performance than those who remain employed at their treatment program. PMID:22527711

  20. Enteroaggregative Escherichia coli in Daycare—A 1-Year Dynamic Cohort Study

    PubMed Central

    Hebbelstrup Jensen, Betina; Stensvold, Christen R.; Struve, Carsten; Olsen, Katharina E. P.; Scheutz, Flemming; Boisen, Nadia; Röser, Dennis; Andreassen, Bente U.; Nielsen, Henrik V.; Schønning, Kristian; Petersen, Andreas M.; Krogfelt, Karen A.

    2016-01-01

    Enteroaggregative Escherichia coli (EAEC) has been associated with persistent diarrhea, reduced growth acceleration, and failure to thrive in children living in developing countries and with childhood diarrhea in general in industrialized countries. The clinical implications of an EAEC carrier-status in children in industrialized countries warrants clarification. To investigate the pathological significance of an EAEC carrier-state in the industrialized countries, we designed a 1-year dynamic cohort study and performed follow-up every second month, where the study participants submitted a stool sample and answered a questionnaire regarding gastrointestinal symptoms and exposures. Exposures included foreign travel, consumption of antibiotics, and contact with a diseased animal. In the capital area of Denmark, a total of 179 children aged 0–6 years were followed in a cohort study, in the period between 2009 and 2013. This is the first investigation of the incidence and pathological significance of EAEC in Danish children attending daycare facilities. Conventional microbiological detection of enteric pathogens was performed at Statens Serum Institute, Copenhagen, Denmark, and at Hvidovre Hospital, Copenhagen, Denmark. Parents completed questionnaires regarding gastrointestinal symptoms. The EAEC strains were further characterized by serotyping, phylogenetic analysis, and susceptibility testing. EAEC was detected in 25 (14%) of the children during the observational period of 1 year. One or more gastrointestinal symptoms were reported from 56% of the EAEC-positive children. Diarrhea was reported in six (24%) of the EAEC positive children, but no cases of weight loss, and general failure to thrive were observed. The EAEC strains detected comprised a large number of different serotypes, confirming the genetic heterogeneity of this pathotype. EAEC was highly prevalent (n = 25, 14%) in Danish children in daycare centers and was accompanied by gastrointestinal symptoms in

  1. The Effect of Clozapine on Hematological Indices: A 1-Year Follow-Up Study.

    PubMed

    Lee, Jimmy; Takeuchi, Hiroyoshi; Fervaha, Gagan; Powell, Valerie; Bhaloo, Amaal; Bies, Robert; Remington, Gary

    2015-10-01

    Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and is linked to a need for mandatory hematological monitoring. Besides agranulocytosis, other hematological aberrations have resulted in premature termination in some cases. Considering clozapine's role in immunomodulation, we proceeded to investigate the impact of clozapine on the following 3 main hematological cell lines: red blood cells, platelets, white blood cells (WBCs), and its differential counts. Data were extracted from patients initiated on clozapine between January 2009 and December 2010 at a single hospital. Patients with a preclozapine complete blood count, who were receiving clozapine during the 1-year follow-up period, were included in the present investigation. Counts of red blood cells, platelets, WBC, and its differential including neutrophils, lymphocytes, monocytes, eosinophils, and basophils were extracted and trajectories plotted. One hundred one patients were included in this study and 66 remained on clozapine at the end of 1 year. There was a synchronized but transient increase in WBC, neutrophils, monocytes, eosinophils, basophils, and platelets beginning as early as the first week of clozapine treatment. There were no cases of agranulocytosis reported in this sample, and five developed neutropenia. A spike in neutrophils immediately preceded the onset of neutropenia in three of the five. The cumulative incidence rates were 48.9% for neutrophilia, 5.9% for eosinophilia, and 3% each for thrombocytosis and thrombocytopenia. Early hematological aberrations are visible across a range of cell lines, primarily of the myeloid lineage. These disturbances are transient and are probably related to clozapine's immunomodulatory properties. We do not suggest discontinuing clozapine as a consequence of the observed aberrations. PMID:26267420

  2. Anhedonia Predicts Major Adverse Cardiac Events and Mortality in Patients 1 Year After Acute Coronary Syndrome

    PubMed Central

    Davidson, Karina W.; Burg, Matthew M.; Kronish, Ian M.; Shimbo, Daichi; Dettenborn, Lucia; Mehran, Roxana; Vorchheimer, David; Clemow, Lynn; Schwartz, Joseph E.; Lespérance, Francois; Rieckmann, Nina

    2010-01-01

    Context Depression is a consistent predictor of recurrent events and mortality in ACS patients, but it has 2 core diagnostic criteria with distinct biological correlates—depressed mood and anhedonia. Objective To determine if depressed mood and/or anhedonia (loss of pleasure or interest) predict 1-year medical outcomes for patients with Acute Coronary Syndrome (ACS). Design Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within one week of admission, patients underwent a structured psychiatric interview to assess clinically impairing depressed mood, anhedonia, and major depressive episode (MDE); also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity. Setting Coronary care and cardiac care step-down units of 3 university hospitals in New York and Connecticut. Participants Consecutive sample of 453 ACS patients (aged 25–93 years; 42% women). Main Outcomes Measures All-cause mortality (ACM) and documented major adverse cardiac events (MACE; myocardial infarction, hospitalization for unstable angina, or urgent revascularization) were actively surveyed for 1 year after admission. Results There were 67 events (16 deaths and 51 MACE; 14.8%). 108 (24%) and 77 (17%) patients with anhedonia and depressed mood, respectively. After controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16–2.14; P<.01) and MDE (adjusted hazard ratio, 1.48; 95% confidence interval, 1.07–2.04; P=.02) were significant predictors of combined MACE/ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes controlling for MDE diagnosis and depressive symptom severity, each of which were no longer significant. Conclusions Anhedonia identifies risk for MACE/ACM beyond that of established medical prognostic indicators

  3. Factors Associated with Caregiver Burden in Dementia: 1-Year Follow-Up Study

    PubMed Central

    Shim, Sang Hong; Kang, Hyo Shin; Kim, Ji Hae

    2016-01-01

    Objective Dementia symptoms (cognitive function, daily-living function, and neuropsychiatric symptoms) become more serious over time, which is likely to increase caregiver burden. The aim of this study is to investigate which dementia-related symptoms, and how the progression of these symptoms, have influenced caregiver burden during a 1-year follow-up assessment. Methods A total of 110 patients with dementia were assessed for their cognitive function, daily-living function, and neuropsychiatric symptoms. Caregivers were assessed for their caregiver burden. Bivariate analyses were conducted between caregiver burden and dementia patients' symptoms, in order to examine which particular symptoms were significantly associated with caregiver burden at the baseline. A multiple regression analysis was then conducted with each significantly associated variable with a view to identifying determinants, influencing caregiver burden. Additionally, bivariate analyses were conducted between the changes in caregiver burden and the changes in patients' symptoms, to investigate which patient variable could best describe caregiver burden from baseline to the 1-year follow-up. A multiple regression analysis was conducted with each significantly-associated change in symptom, in order to identify determinants that influence a change in caregiver burden. Results Neuropsychiatric symptoms, such as irritability, aberrant motor-behavior, delusions and disinhibition were found to be significant predictors of caregiver burden at baseline, according to multiple regression analysis. In addition, changes in neuropsychiatric symptoms, such as delusions, agitation and memory-related functioning in daily-living significantly predict a change in caregiver burden. Conclusion Our results demonstrate that neuropsychiatric symptoms and memory impairment in daily-living functions are significant predictors of an increase in caregiver burden. PMID:26766945

  4. Glomerular filtration rate in patients with atrial fibrillation and 1-year outcomes

    PubMed Central

    Boriani, Giuseppe; Laroche, Cécile; Diemberger, Igor; Popescu, Mircea Ioachim; Rasmussen, Lars Hvilsted; Petrescu, Lucian; Crijns, Harry J. G. M.; Tavazzi, Luigi; Maggioni, Aldo P.; Lip, Gregory Y. H.

    2016-01-01

    We assessed 1-year outcomes in patients with atrial fibrillation enrolled in the EurObservational Research Programme AF General Pilot Registry (EORP-AF), in relation to kidney function, as assessed by glomerular filtration rate (eGFR). In a cohort of 2398 patients (median age 69 years; 61% male), eGFR (ml/min/1.73 m2) calculated using the CKD-EPI formula was ≥80 in 35.1%, 50–79 in 47.2%, 30–49 in 13.9% and <30 in 3.7% of patients. In a logistic regression analysis, eGFR category was an independent predictor of stroke/TIA or death, with elevated odds ratios associated with severe to mild renal impairment, ie. eGFR < 30 ml/min/1.73 m2 [OR 3.641, 95% CI 1.572–8.433, p < 0.0001], 30–49 ml/min/1.73 m2 [OR 3.303, 95% CI 1.740–6.270, p = 0.0026] or 50–79 ml/min/1.73 m2 [OR 2.094, 95% CI 1.194–3.672, p = 0.0003]. The discriminant capability for the risk of death was tested among various eGFR calculation algorithms: the best was the Cockcroft-Gault equation adjusted for BSA, followed by Cockcroft-Gault equation, and CKD-EPI equation, while the worst was the MDRD equation. In conclusion in this prospective observational registry, renal function was a major determinant of adverse outcomes at 1 year, and even mild or moderate renal impairments were associated with an increased risk of stroke/TIA/death. PMID:27466080

  5. Perinatal dioxin exposure and the neurodevelopment of Vietnamese toddlers at 1 year of age.

    PubMed

    Pham, Tai The; Nishijo, Muneko; Nguyen, Anh Thi Nguyet; Tran, Nghi Ngoc; Van Hoang, Luong; Tran, Anh Hai; Nguyen, Trung Viet; Nishijo, Hisao

    2015-12-01

    Dioxin concentrations remain elevated in both the environment and in humans residing near former US Air Force bases in South Vietnam. This may potentially have adverse health effects, particularly on infant neurodevelopment. We followed 214 infants whose mothers resided in a dioxin-contaminated area in Da Nang, Vietnam, from birth until 1 year of age. Perinatal exposure to dioxins was estimated from toxic equivalent (TEQ) levels of polychlorinated dibenzodioxins and polychlorinated dibenzofurans (PCDDs/Fs-TEQ), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TetraCDD) concentrations in breast milk. In infants, daily dioxin intake (DDI) was used as an index of postnatal exposure through breastfeeding. Neurodevelopment of toddlers was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). No significant differences in neurodevelopmental scores were exhibited for cognitive, language or motor functions between four exposure groups of PCDDs/Fs-TEQ or 2,3,7,8-TetraCDD. However, social-emotional scores were decreased in the high PCDDs/Fs-TEQ group and the high 2,3,7,8-TetraCDD group compared with those with mild exposure, after adjusting for confounding factors. Cognitive scores in the mild, moderate, and high DDI groups were significantly higher than those in low DDI group, but there were no differences in cognitive scores among the three higher DDI groups. These results suggest that perinatal exposure to dioxins may affect social-emotional development of 1-year-old toddlers, without diminishing global neurodevelopmental function. PMID:26247686

  6. Memantine and brain atrophy in Alzheimer's disease: a 1-year randomized controlled trial.

    PubMed

    Wilkinson, David; Fox, Nick C; Barkhof, Frederik; Phul, Ravinder; Lemming, Ole; Scheltens, Philip

    2012-01-01

    The primary objective of this study was to evaluate the rate of total brain atrophy (TBA) with serial magnetic resonance imaging (MRI), using the Brain Boundary Shift Integral (BBSI), in patients with probable Alzheimer's disease (AD) over the course of 52 weeks of treatment with memantine or placebo. This was a multi-national, randomized, double-blind, placebo-controlled, fixed-dose 1-year study. Patients were randomized (1 : 1) to treatment with placebo or memantine. Patients randomized to memantine were up-titrated to the target dose of 20 mg/day over 4 weeks. MRI scans were collected at screening and at Weeks 4, 42, and 52. Secondary efficacy assessments included several cognitive and behavioral scales. 518 patients were screened, 278 patients were randomized, and 217 patients completed the study. In the primary efficacy analysis, the differences in TBA rates between memantine (15.2 mL/year) and placebo (15.3 mL/year) were not statistically significant (-0.04 mL/year [(95% CI: -2.60, 2.52), p = 0.98]). There was a statistically significant correlation between change in TBA and change in most cognitive and behavioral scale scores. Patients who were not treated with acetyl cholinesterase inhibitors (AChEIs) showed a significantly lower TBA rate than patients treated with AChEIs. Memantine had a placebo-level incidence of adverse events. There were no statistically significant differences between memantine and placebo in total brain or hippocampal atrophy rates in patients with probable AD treated for 1 year. The biological relevance of cerebral atrophy was supported by a significant correlation between rate of atrophy and decline in cognitive and behavioral outcomes. PMID:22269160

  7. Metabolic Changes Following a 1-Year Diet and Exercise Intervention in Patients With Type 2 Diabetes

    PubMed Central

    Albu, Jeanine B.; Heilbronn, Leonie K.; Kelley, David E.; Smith, Steven R.; Azuma, Koichiro; Berk, Evan S.; Pi-Sunyer, F. Xavier; Ravussin, Eric

    2010-01-01

    OBJECTIVE To characterize the relationships among long-term improvements in peripheral insulin sensitivity (glucose disposal rate [GDR]), fasting glucose, and free fatty acids (FFAs) and concomitant changes in weight and adipose tissue mass and distribution induced by lifestyle intervention in obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS We measured GDR, fasting glucose, and FFAs during a euglycemic clamp and adipose tissue mass and distribution, organ fat, and adipocyte size by dual-energy X-ray absorptiometry, CT scan, and adipose tissue biopsy in 26 men and 32 women in the Look-AHEAD trial before and after 1 year of diet and exercise aimed at weight loss. RESULTS Weight and fasting glucose decreased significantly (P < 0.0001) and significantly more in men than in women (−12 vs. −8% and −16 vs. −7%, respectively; P < 0.05), while FFAs during hyperinsulinemia decreased and GDR increased significantly (P < 0.00001) and similarly in both sexes (−53 vs. −41% and 63 vs. 43%; P = NS). Men achieved a more favorable fat distribution by losing more from upper compared with lower and from deeper compared with superficial adipose tissue depots (P < 0.01). Decreases in weight and adipose tissue mass predicted improvements in GDR but not in fasting glucose or fasting FFAs; however, decreases in FFAs during hyperinsulinemia significantly determined GDR improvements. Hepatic fat was the only regional fat measure whose change contributed independently to changes in metabolic variables. CONCLUSIONS Patients with type 2 diabetes undergoing a 1-year lifestyle intervention had significant improvements in GDR, fasting glucose, FFAs and adipose tissue distribution. However, changes in overall weight (adipose tissue mass) and hepatic fat were the most important determinants of metabolic improvements. PMID:20028945

  8. Infant Aphakia Treatment Study: Effects of persistent fetal vasculature on outcome at 1 year of age

    PubMed Central

    Morrison, David G.; Wilson, M. Edward; Trivedi, Rupal H.; Lambert, Scott R.; Lynn, Michael J.

    2011-01-01

    Background The Infant Aphakia Treatment Study (IATS) is a randomized trial comparing the treatment of unilateral congenital cataract with primary intraocular lens (IOL) implantation versus aphakic contact lens (CL). The purpose of this study was to compare the outcomes for infants with lens opacity associated with persistent fetal vasculature (PFV) to those without. Methods Retrospective subgroup analysis of grating visual acuity at 1 year of age and adverse events up to 1 year after surgery in eyes identified intraoperatively as having evidence of mild PFV from the IATS. Results Of 83 infants, 18 (22%: 11 CL, 7 IOL) had PFV. Median logMAR visual acuity was 0.88 for patients with PFV and 0.80 for patients without PFV (P = 0.46). One or more adverse events up to one year after surgery occurred in 12 infants (67%) with PFV and 30 infants (46%) without PFV (P = 0.18). The incidence of adverse events was significantly higher in patients with PFV compared to patients without PFV in the CL group (55% vs 20%, P = 0.049) but not in the IOL group (86% vs 71%, P = 0.65), possibly because all children receiving IOLs had higher rates of adverse events when compared to aphakic children (73% vs 29%, P < 0.001). Conclusions Aphakic infants with mild PFV treated with CL had a higher incidence of adverse events following lensectomy compared to children with other forms of unilateral congenital cataract; nevertheless, similar visual outcomes at one year after surgery were obtained. PMID:22108353

  9. Glomerular filtration rate in patients with atrial fibrillation and 1-year outcomes.

    PubMed

    Boriani, Giuseppe; Laroche, Cécile; Diemberger, Igor; Popescu, Mircea Ioachim; Rasmussen, Lars Hvilsted; Petrescu, Lucian; Crijns, Harry J G M; Tavazzi, Luigi; Maggioni, Aldo P; Lip, Gregory Y H

    2016-01-01

    We assessed 1-year outcomes in patients with atrial fibrillation enrolled in the EurObservational Research Programme AF General Pilot Registry (EORP-AF), in relation to kidney function, as assessed by glomerular filtration rate (eGFR). In a cohort of 2398 patients (median age 69 years; 61% male), eGFR (ml/min/1.73 m(2)) calculated using the CKD-EPI formula was ≥80 in 35.1%, 50-79 in 47.2%, 30-49 in 13.9% and <30 in 3.7% of patients. In a logistic regression analysis, eGFR category was an independent predictor of stroke/TIA or death, with elevated odds ratios associated with severe to mild renal impairment, ie. eGFR < 30 ml/min/1.73 m(2) [OR 3.641, 95% CI 1.572-8.433, p < 0.0001], 30-49 ml/min/1.73 m(2) [OR 3.303, 95% CI 1.740-6.270, p = 0.0026] or 50-79 ml/min/1.73 m2 [OR 2.094, 95% CI 1.194-3.672, p = 0.0003]. The discriminant capability for the risk of death was tested among various eGFR calculation algorithms: the best was the Cockcroft-Gault equation adjusted for BSA, followed by Cockcroft-Gault equation, and CKD-EPI equation, while the worst was the MDRD equation. In conclusion in this prospective observational registry, renal function was a major determinant of adverse outcomes at 1 year, and even mild or moderate renal impairments were associated with an increased risk of stroke/TIA/death. PMID:27466080

  10. Endovascular stents in children under 1 year of age: acute impact and late results.

    PubMed Central

    Hatai, Y.; Nykanen, D. G.; Williams, W. G.; Freedom, R. M.; Benson, L. N.

    1995-01-01

    OBJECTIVES--To review efficacy and safety of endovascular stent implants in children < 1 year of age with congenital heart lesions. DESIGN--Retrospective study of patients in a tertiary care setting. PATIENTS--26 children (median age of 4.7 months, range 2 days to 1 year) with various vascular obstructive lesions. INTERVENTION--Percutaneous or intraoperative implantation of balloon expandable endovascular stents. RESULTS--Optimal stent placement was obtained in 31 of the 37 deployed implants. Complications resulted primarily from stent malpositioning and one episode of bleeding at a puncture site. Stent implantation in three patients with a restrictive arterial duct allowed for patency and five patients with conduit stenosis had mean (SD) right ventricule to systemic artery pressure ratios falling from 0.99 (0.20) to 0.52 (0.18) (P < 0.05). In 10 patients with pulmonary artery stenosis, the mean vessel diameter increased from 2.8 (0.9) mm to 5.8 (1.4) mm (P << 0.001). No clinical improvement was seen in two patients because of diffuse hypoplasia of the pulmonary vessels. Nine of 10 patients with miscellaneous obstructive lesions improved clinically. Recatheterisation was performed in 19 patients (median 8 months, range 12 days to 28 months) and 11 patients required redilatation (17 stents). CONCLUSIONS--Stent implantation is technically feasible in infants and under specific circumstances may provide an alternative to surgical palliation or avoid reoperation. The long term impact on clinical course, however, involves further interventions directed at stent management. Images PMID:8541180

  11. A longitudinal study of back dimension changes over 1 year in sports horses.

    PubMed

    Greve, Line; Dyson, Sue

    2015-01-01

    Major back dimension changes over time have been observed in some horses, the speed of which may be influenced by work type, skeletal maturity, nutrition and saddle fit. Currently, there are no longitudinal data quantifying changes in back dimensions. The objectives of this study were to quantify back dimension changes over time, to identify the effects of horse, saddle and rider on these dimensions, and to determine their association with season, weight, work and saddle management. A prospective, longitudinal study was performed, using stratified random sampling within a convenience sample of 104 sports horses in normal work. Thoracolumbar dimensions/symmetry were measured at predetermined sites every second month over 1 year; weight, work and saddle management changes were recorded. Descriptive statistics, and univariable and multiple mixed effects linear regression were performed to assess the association between management changes, horse-saddle-rider factors and back dimension changes. Complete data was available for 63/104 horses, including horses used for dressage (n= 26), showjumping (n= 26), eventing (n= 26) and general purpose (n= 26), with age groups 3-5 years (n = 24), 6-8 years (n = 28), 9-12 years (n = 24) and ≥ 13 years (n = 28). There were considerable variations in back dimensions over 1 year. In the multivariable analysis, the presence of gait abnormalities at initial examination and back asymmetry were significant and had a negative effect on changes in back dimensions. Subsequent improved saddle fit, similar or increased work intensity, season (summer versus winter) and increased bodyweight retained significance, having positive effects on changes in back dimensions. In conclusion, quantifiable changes in back dimensions occur throughout the year. Saddle fit should be reassessed professionally several times a year, especially if there has been a change in work intensity. PMID:25510314

  12. Five-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs

    PubMed Central

    Lin, Jessica J.; Cardarella, Stephanie; Lydon, Christine A.; Dahlberg, Suzanne E.; Jackman, David M.; Jänne, Pasi A.; Johnson, Bruce E.

    2016-01-01

    Introduction Activating mutations in the epidermal growth factor receptor (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy. Long-term survival outcomes, however, remain undefined. The objective of this study was to determine the 5-year survival in these patients, and identify clinical factors associated with overall survival (OS). Methods Patients with EGFR-mutant metastatic lung adenocarcinoma treated with erlotinib or gefitinib at Dana-Farber Cancer Institute between 2002 and 2009 were included. OS was analyzed. Results Among 137 patients, median PFS and OS were 12.1 months (95% CI, 10.2-13.5 months) and 30.9 months (95% CI, 28.2-35.7 months), respectively. Twenty patients (14.6%) were 5-year survivors. In multivariate analysis, exon 19 deletions (hazard ratio [HR], 0.63; 95% CI, 0.44-0.91; P = 0.01), absence of extrathoracic (HR 0.62; 95% CI, 0.41-0.93; P = 0.02) or brain metastasis (HR 0.48; 95% CI, 0.30-0.77, P = 0.002), and not a current smoker (HR 0.23; 95% CI, 0.09-0.59; P = 0.002) were associated with prolonged OS. Age, gender, stage at diagnosis, liver or bone or adrenal metastasis, specific TKI, and line of TKI therapy were not associated with OS. Conclusions Our data suggest that the prevalence of 5-year survival among EGFR-mutant metastatic lung adenocarcinoma patients treated with erlotinib or gefitinib is 14.6%. Exon 19 deletions and absence of extrathoracic or brain metastasis are associated with prolonged survival. Based on our findings, clinicians can gain an enhanced estimation of long-term outcomes in this population. PMID:26724471

  13. The pretreatment albumin to globulin ratio predicts survival in patients with natural killer/T-cell lymphoma

    PubMed Central

    Bi, Xi-wen; Wang, Liang; Zhang, Wen-wen; Yan, Shu-mei; Sun, Peng; Xia, Yi; Li, Zhi-ming

    2016-01-01

    Background. The pretreatment albumin to globulin ratio (AGR) has been reported to be a predictor of survival in several types of cancer. The aim of this study was to evaluate the prognostic impact of AGR in patients with natural killer/T-cell lymphoma (NKTCL). Methods. We retrospectively reviewed the available serum biochemistry results for 331 NKTCL patients before treatment. AGR was calculated as albumin/(total protein—albumin), and a cut-off value of 1.3 was used to define AGR as low or high. Survival analysis was used to assess the prognostic value of AGR. Results. A low AGR (<1.3) was associated with significantly more adverse clinical features, including old age, poor performance status, advanced stage, elevated lactate dehydrogenase, B symptoms, and high International Prognostic Index (IPI) and natural killer/T-cell lymphoma prognostic index (NKPI) scores. Patients with a low AGR had a significantly lower 5-year overall survival (44.5 vs. 65.2%, P < 0.001) and progression-free survival (33.1 vs. 57.4%, P < 0.001). In the multivariate analysis, a low AGR remained an independent predictor of poorer survival. Additionally, AGR distinguished patients with different outcomes in the IPI low-risk group and in the NKPI high-risk group. Discussion. Pretreatment AGR may serve as a simple and effective predictor of prognosis in patients with NKTCL. PMID:26966671

  14. High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma

    PubMed Central

    Cheng, W-F; Huang, C-Y; Chang, M-C; Hu, Y-H; Chiang, Y-C; Chen, Y-L; Hsieh, C-Y; Chen, C-A

    2009-01-01

    The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, P<0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23–3.37) P=0.006) and OS (3.72 (1.64–8.45), P=0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76–125.60), P=0.013) or suboptimal (4.47 (1.83–10.88), P=0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC. PMID:19293794

  15. Incidence, Predictors and Impact of Severe Periprocedural Bleeding According to VARC-2 Criteria on 1-Year Clinical Outcomes in Patients After Transcatheter Aortic Valve Implantation.

    PubMed

    Kochman, Janusz; Rymuza, Bartosz; Huczek, Zenon; Kołtowski, Łukasz; Ścisło, Piotr; Wilimski, Radosław; Ścibisz, Anna; Stanecka, Paulina; Filipiak, Krzysztof J; Opolski, Grzegorz

    2016-01-01

    There are differences in reporting bleeding complications after transcatheter aortic valve implantation (TAVI), which is a consequence of the lack of consensus for their definition. Furthermore, the amount of data on the impact of peri-procedural bleeding on the mid-term prognosis is still limited. The aim of this study was to investigate the incidence, predictors, and impact of life-threatening and major bleedings as defined by the Valve Academic Research Consortium 2 (VARC-2) in patients after TAVI over the mid-term prognosis.Consecutive patients who underwent TAVI from March 2010 to December 2013 were included. All data were classified according to the VARC-2 criteria. We assessed the incidence and the predictors of serious bleeding events (SBE), defined as life-threatening/disabling (LT/D) or major bleeding, and analyzed their impact on 30-day and 1-year clinical outcome.A total of 129 patients were included (79.1 ± 8.3 years; mean EuroSCORE = 17.8 ± 12.7). The SBE occurred in 25 patients (19.4%), of which 9 (7.0%) had LT/D and 16 (12.4%) had major bleeding. Trans-subclavian (TS) access (OR 4.38, 95% CI 2.13-14.29, P = 0.01) and diabetes (OR 2.93, 95% CI 1.08-7.93, P = 0.03) were identified as independent predictors of SBE. Patients with SBE had higher 30-day mortality (20.0% versus 4.0% P = 0.02) and 1-year mortality (40.0% versus 11.1%, P < 0.002). SBE independently predicted 1-year, all-cause mortality (HR 5.88, 95% CI 1.7319,94, P = 0.005).SBE are frequent after TAVI and are associated with decreased short and mid-term survival. Diabetes and TS access are independent risk factors for SBE. PMID:26673439

  16. Survival of extreme opinions

    NASA Astrophysics Data System (ADS)

    Hsu, Jiann-wien; Huang, Ding-wei

    2009-12-01

    We study the survival of extreme opinions in various processes of consensus formation. All the opinions are treated equally and subjected to the same rules of changing. We investigate three typical models to reach a consensus in each case: (A) personal influence, (B) influence from surroundings, and (C) influence to surroundings. Starting with uniformly distributed random opinions, our calculated results show that the extreme opinions can survive in both models (A) and (B), but not in model (C). We obtain a conclusion that both personal influence and passive adaptation to the environment are not sufficient enough to eradicate all the extreme opinions. Only the active persuasion to change the surroundings eliminates the extreme opinions completely.

  17. Doubly robust survival trees.

    PubMed

    Steingrimsson, Jon Arni; Diao, Liqun; Molinaro, Annette M; Strawderman, Robert L

    2016-09-10

    Estimating a patient's mortality risk is important in making treatment decisions. Survival trees are a useful tool and employ recursive partitioning to separate patients into different risk groups. Existing 'loss based' recursive partitioning procedures that would be used in the absence of censoring have previously been extended to the setting of right censored outcomes using inverse probability censoring weighted estimators of loss functions. In this paper, we propose new 'doubly robust' extensions of these loss estimators motivated by semiparametric efficiency theory for missing data that better utilize available data. Simulations and a data analysis demonstrate strong performance of the doubly robust survival trees compared with previously used methods. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27037609

  18. How worms survive desiccation

    PubMed Central

    Erkut, Cihan; Penkov, Sider; Fahmy, Karim; Kurzchalia, Teymuras V.

    2012-01-01

    While life requires water, many organisms, known as anhydrobiotes, can survive in the absence of water for extended periods of time. Although discovered 300 years ago, we know very little about the fascinating phenomenon of anhydrobiosis. In this paper, we summarize our previous findings on the desiccation tolerance of the Caenorhabditis elegans dauer larva. A special emphasis is given to the role of trehalose in protecting membranes against desiccation. We also propose a simple mechanism for this process. PMID:24058825

  19. Cracking the survival code

    PubMed Central

    Füllgrabe, Jens; Heldring, Nina; Hermanson, Ola; Joseph, Bertrand

    2014-01-01

    Modifications of histones, the chief protein components of the chromatin, have emerged as critical regulators of life and death. While the “apoptotic histone code” came to light a few years ago, accumulating evidence indicates that autophagy, a cell survival pathway, is also heavily regulated by histone-modifying proteins. In this review we describe the emerging “autophagic histone code” and the role of histone modifications in the cellular life vs. death decision. PMID:24429873

  20. Survivable Optical WDM Networks

    NASA Astrophysics Data System (ADS)

    Ou, Canhui (Sam); Mukherjee, Biswanath

    Survivable Optical WDM Networks investigates different approaches for designing and operating an optical network with the objectives that (1) more connections can be carried by a given network, leading to more revenue, and (2) connections can recover faster in case of failures, leading to better services. Different networks - wavelength-routed WDM networks, wavelength-routed WDM networks with sub-wavelength granularity grooming, and data over next-generation SONET/SDH over WDM networks - are covered.

  1. Observational Study of 1-Year Mortality Rates Before and After a Major Earthquake Among Chinese Nonagenarians

    PubMed Central

    Dong, Birong; Wu, Hongmei; Zhang, Yanling; Guralnik, Jack M.; Malmstrom, Theodore K.; Morley, John E.

    2011-01-01

    Background. Little is known about mortality among nonagenarians after an earthquake. Methods. Using secondary data analyses from the 2005 study called the Project of Longevity and Aging in Dujiangyan(n = 870), 1-year mortality rates were compared among a pre-earthquake group and a post-earthquake group of nonagenarians. All participants were from Dujiangyan, 50 km from the epicenter of the May 12, 2008 earthquake, in China. The pre-earthquake group was a subset of the 870 Project of Longevity and Aging in Dujiangyan participants, ages 93–95 years at the beginning of “Time Frame 1” (July 2005 through June 2006; n = 228). The post-earthquake group was a different subset of the 870 Project of Longevity and Aging in Dujiangyan participants, ages 93–95 years and alive at the beginning of Time Frame 2 (July 2008 through June 2009; n = 235). Time Frame 2 excluded a 7-week period following the earthquake in order to account for deaths due to trauma. Pre-earthquake health assessment data from the 2005 Project of Longevity and Aging in Dujiangyan study were used to calculate unadjusted/adjusted hazard ratios (HRs) for mortality. Results. One-year mortality rates were 8.3% (19/228) and 16.2% (38/235) in the pre-earthquake group and the post-earthquake group, respectively (p =.01). In unadjusted analyses, only “being in the post-earthquake group” was associated with death (HR = 2.04; 95% confidence interval [CI], 1.17–3.53; p = .011). In the multivariable Cox regression model, being in the post-earthquake group continued to be the strongest risk factor associated with mortality (HR = 2.47; 95% CI, 1.39–4.40; p = .002). Other significant risk factors included impaired cognition (HR = 1.97; 95% CI, 1.10–3.53; p = .024), serum albumin (HR = 0.90; 95% CI, 0.82–0.98; p < .015), and serum triglycerides (HR = 1.51; 95% CI, 1.15–1.99; p = .003). Conclusion. The May 12, 2008 earthquake in Wenchuan, China, was associated with a twofold increase in the 1-year

  2. Carbonaceous Survivability on Impact

    NASA Technical Reports Server (NTRS)

    Bunch, T. E.; Becker, Luann; Morrison, David (Technical Monitor)

    1994-01-01

    In order to gain knowledge about the potential contributions of comets and cosmic dust to the origin of life on Earth, we need to explore the survivability of their potential organic compounds on impact and the formation of secondary products that may have arisen from the chaotic events sustained by the carriers as they fell to Earth. We have performed a series of hypervelocity impact experiments using carbon-bearing impactors (diamond, graphite, kerogens, PAH crystals, and Murchison and Nogoya meteorites) into Al plate targets at velocities - 6 km/s. Estimated peak shock pressures probably did not exceed 120 GPa and peak shock temperatures were probably less than 4000 K for times of nano- to microsecs. Nominal crater dia. are less than one mm. The most significant results of these experiments are the preservation of the higher mass PAHs (e. g., pyrene relative to napthalene) and the formation of additional alkylated PAHs. We have also examined the residues of polystyrene projectiles impacted by a microparticle accelerator into targets at velocities up to 15 km/s. This talk will discuss the results of these experiments and their implications with respect to the survival of carbonaceous deliverables to early Earth. The prospects of survivability of organic molecules on "intact" capture of cosmic dust in space via soft: and hard cosmic dust collectors will also be discussed.

  3. Residential property values predict prevalent obesity but do not predict 1 year weight change

    PubMed Central

    Drewnowski, Adam; Aggarwal, Anju; Tang, Wesley; Moudon, Anne Vernez

    2014-01-01

    Objective Lower socioeconomic status (SES) has been linked with higher obesity rates but not with weight gain. This study examined whether SES can predict short-term weight change. Design and Methods The Seattle Obesity Study II was based on an observational cohort of 440 adults. Weights and heights were measured at baseline and at 1 y. Self-reported education and incomes were obtained by questionnaire. Home addresses were linked to tax parcel property values from the King Co. tax assessor. Associations among SES variables, prevalent obesity, and 1 y weight change were examined using multivariable linear regressions. Results Low residential property values at tax parcel predicted prevalent obesity at baseline and at 1 y. Living in the top quartile of house prices reduced obesity risk by 80% at both time points. At 1 year, about 38% of the sample lost >1kg body weight; 32% maintained (± 1kg), and 30% gained >1kg. In adjusted models, none of the baseline SES measures had any impact on 1 y weight change. Conclusions SES variables, including tax parcel property values predicted prevalent obesity but did not predict short-term weight change. These findings, based on longitudinal cohort data, suggest other mechanisms are involved in short-term weight change. PMID:25684713

  4. Hydrocephalus in children less than 1 year of age in northern Mozambique

    PubMed Central

    Salvador, Sérgio F.; Henriques, João Carlos; Munguambe, Missael; Vaz, Rui M. C.; Barros, Henrique P.

    2014-01-01

    Background: In developed countries, the incidence of neonatal hydrocephalus ranges from 3 to 5 cases per 1000 live births, but little is known about the frequency of hydrocephalus in Africa. In Mozambique, there is no primary information related to this disorder, but using the above data, the expected incidence of neonatal hydrocephalus would range from 2900 to 4800 cases per year. Methods: This study is based on 122 children younger than 1 year with neonatal hydrocephalus, followed up between January 2010 and December 2012, their origin and treatment, and aims to evaluate difficulties with diagnosis, treatment, and follow-up in northern Mozambique. Results: Identified cases were mainly less than 6 months old (77%), with severe macrocephaly and the classic stigmata of this condition. A high rate of follow-up loss (44.3%) was detected, particularly among children from more distant locations. Our findings contrast with the expected 1000-1700 cases that would occur in the area during the study period, being considerably lower. Conclusions: Hydrocephalus is a serious problem in sub-Saharan Africa, whose effects can be minimized by a better organization of the health system in hydrocephalus prevention, referral, and follow-up. New management alternatives to provide treatment to more children with this disorder and reduction of the follow-up difficulties caused due to geographical reasons for the children undergoing treatment are essential. PMID:25593759

  5. Effect of iodine supplementation during pregnancy on infant neurodevelopment at 1 year of age.

    PubMed

    Murcia, Mario; Rebagliato, Marisa; Iñiguez, Carmen; Lopez-Espinosa, Maria-Jose; Estarlich, Marisa; Plaza, Belén; Barona-Vilar, Carmen; Espada, Mercedes; Vioque, Jesús; Ballester, Ferran

    2011-04-01

    Iodine is the main constituent of thyroid hormones, which in turn are required for fetal brain development. However, the relation between iodine intake during pregnancy, thyroid function, and child neurodevelopment needs further evaluation. The authors assessed the association of maternal iodine intake from diet and supplements during pregnancy and of maternal and neonatal thyroid function with infant neurodevelopment. The Mental Development Index and Psychomotor Development Index (PDI) for 691 children were obtained between 2005 and 2007 using the Bayley Scales of Infant Development at age 1 year in a prebirth cohort in Valencia, Spain. In multivariate analyses, a maternal thyrotropin level >4 μU/mL was associated with an increased risk of a PDI <85 (odds ratio = 3.5, P = 0.02). Maternal intake of ≥150 μg/day, compared with <100 μg/day, of iodine from supplements was associated with a 5.2-point decrease in PDI (95% confidence interval: -8.1, -2.2) and a 1.8-fold increase in the odds of a PDI <85 (95% confidence interval: 1.0, 3.3). When analyses were stratified by sex, this association was intensified for girls but was not observed for boys. Further evidence on the safety and effectiveness of iodine supplementation during pregnancy is needed before it is systematically recommended in iodine-sufficient or mildly deficient areas. PMID:21385833

  6. Ablation for atrial fibrillation during mitral valve surgery: 1-year results through continuous subcutaneous monitoring.

    PubMed

    Bogachev-Prokophiev, Alexandr; Zheleznev, Sergey; Romanov, Alexander; Pokushalov, Evgeny; Pivkin, Alexey; Corbucci, Giorgio; Karaskov, Alexander

    2012-07-01

    Continuous monitoring of cardiac rhythm may play an important role in measuring the true symptomatic/asymptomatic atrial fibrillation (AF) burden and improve the management of anti-arrhythmic and anti-thrombotic therapies. Forty-seven patients with mitral valve disease and longstanding persistent AF (LSPAF) underwent a left atrial maze procedure with bipolar radiofrequency and valve surgery. The follow-up data recorded by an implanted loop recorder were analysed after 3, 6 and 12 months. On discharge, 40 (85.1%) patients were in stable sinus rhythm, as documented by in-office electrocardiography (ECG), 4 (8.5%) were in pacemaker rhythm and 3 (6.4%) were in AF. One (2.1%) patient died after 7 months. On 12-month follow-up examination, 30 (65.2%) patients had an AF burden <0.5% and were classified as responders. Three (6.5%) of the 16 non-responders had atrial flutter and 13 (27.7%) had documented AF recurrences with an AF burden >0.5%. Two (4.3%) patients with AF recurrences were completely asymptomatic. Among the symptomatic events stored by the patients, only 27.6% was confirmed as genuine AF recurrences according to the concomitant ECG recorded by the implanted loop recorder. A concomitant bipolar maze procedure during mitral valve surgery is effective in treating AF, as proved by detailed 1-year continuous monitoring. PMID:22514258

  7. A 1-year follow-up of implants of differing surface roughness placed in rabbit bone.

    PubMed

    Wennerberg, A; Ektessabi, A; Albrektsson, T; Johansson, C; Andersson, B

    1997-01-01

    Screw-shaped implants were prepared with three different surface topographies: One was left as machined, ie, a turned surface, and two were blasted surfaces with differing degrees of surface roughness. The surface topography was measured with a confocal laser scanning profilometer and the surface roughness was characterized using height and spatial descriptive parameters. The turned surface had an average surface roughness of 0.96 micron and an average peak spacing of 8.6 microns. The two blasted surfaces had surface roughness values of 1.16 microns and 1.94 microns, respectively; the corresponding values for the peak spacing parameter were 10.00 microns and 13.22 microns, respectively. After 1 year in rabbit bone, the bone response to the turned implants was compared with the response to the two blasted implant surfaces. Firmer bone fixation was found for the two blasted surfaces, with statistically significant increases in removal torque and percentage of bone-to-metal contact. Furthermore, about 2 mm from the implant surface, the titanium release was similar for the turned and the 25-micron aluminum oxide-blasted implants. PMID:9274077

  8. Effectiveness of sealing active proximal caries lesions with an adhesive system: 1-year clinical evaluation.

    PubMed

    Abuchaim, Clarisse; Rotta, Marina; Grande, Rosa Helena Miranda; Loguercio, Alessandro Dourado; Reis, Alessandra

    2010-01-01

    The objective of this study was to evaluate the effectiveness of a therapeutic sealant to arrest non-cavitated proximal carious lesion progression. The study population comprised 44 adolescents who had bitewing radiographs taken for caries diagnosis. Non-cavitated lesions extending up to half of dentin thickness were included in the sample. In the experimental group (n = 33), the proximal caries-lesion surfaces were sealed with an adhesive (OptiBond Solo, Kerr) after tooth separation. The control group (n = 11) received no treatment, except for oral hygiene instructions including use of dental floss. Follow-up radiographs were taken after one year and were analyzed in comparison with baseline radiographs. In a blind study setting, visual readings were performed by two examiners, blinded to whether the examined radiograph was baseline or follow-up, and whether it concerned a test or control lesion. The efficacy of sealing treatment was evaluated by the McNemar test (0.05). About 22% of the sealed lesions showed reduction, 61% showed no change and 16% showed progression. For the control lesions, the corresponding values were 27%, 36% and 36% respectively. The number of lesions that showed reduction and no changes were merged and therefore 83.3% of the sealed lesions and 63.6% of the control lesions were considered clinically successful. No statistical significance was detected (p > 0.05). In the course of 1 year, sealing proximal caries lesions was not shown to be superior to lesion monitoring. PMID:20877976

  9. Temporal associations between disordered eating and nonsuicidal self-injury: examining symptom overlap over 1 year.

    PubMed

    Turner, Brianna J; Yiu, Angelina; Layden, Brianne K; Claes, Laurence; Zaitsoff, Shannon; Chapman, Alexander L

    2015-01-01

    Disordered eating (DE) and nonsuicidal self-injury (NSSI) commonly co-occur. This study compared several models of the longitudinal relationship between DE and NSSI, including concurrent and prospective models, and examined the possible moderating roles of self-objectification, impulsivity, and emotion dysregulation in these relationships. Individuals with NSSI (N=197) recruited from online forums completed measures of NSSI and DE every 3 months for 1 year. We tested the associations between NSSI and DE using hierarchical linear models. Results supported a concurrent relationship, wherein frequency of NSSI positively covaried with concurrent DE severity. Body surveillance moderated the concurrent relationship between NSSI and DE. Individuals who engaged in more body surveillance endorsed high levels of DE pathology, whereas those lower in body surveillance engaged in more frequent NSSI only at higher levels of DE. In addition, whereas DE did not prospectively predict NSSI, frequency of NSSI predicted more severe DE 3 months later. The prospective relationship between DE and later NSSI was moderated by emotion dysregulation, such that highly dysregulated individuals had a stronger relationship between DE and later NSSI, whereas this relationship was not significant among individuals low in emotion dysregulation. These findings add valuable information regarding the co-occurrence of self-damaging behaviors. PMID:25526840

  10. Congenital abnormality of the vagina complicated by haemato-pyocolpos in a 1-year labrador retriever.

    PubMed

    Alonge, S; Romussi, S; Grieco, V; Luvoni, G C

    2015-06-01

    A 1-year-old female Labrador retriever was referred with a few days history of haematic-like vulvar discharge. Physical examination, vaginal inspection and palpation did not reveal any remarkable finding. Transabdominal ultrasound showed echogenic fluid accumulation in the vagina suggesting haemato-pyocolpos. An exploratory laparotomy was performed: a well-delimited ectasic vagina was identified. Ovariohysterectomy and partial vaginectomy and vaginoplasty were performed to spay the bitch and to remove the ectasic vagina. Post-operative recovery and 12-month follow-up were uneventful. Clinical, morphological and histological findings were consistent with a congenital abnormality of the muscular layer of the vagina complicated by haemato-pyocolpos. The disorganization of the vaginal tunica muscularis may have acted as locus minoris resistentiae in the vaginal wall. The organ was dilated and atonic due to the gradual accumulation of physiological fluids complicated by an overgrowth of genital bacteria. This congenital disorder has to be taken into account as differential diagnosis of haemato-pyocolpos with vaginal discharge in young bitches. PMID:25661902

  11. Laboratory Tests Ordered By a Chiropractic Sports Physician on Elite Athletes Over a 1-Year Period

    PubMed Central

    Nabhan, Dustin C.; Moreau, William J.; Barylski, Chad

    2015-01-01

    Objective The purpose of this study is to describe and discuss laboratory tests ordered on elite athletes in an interdisciplinary sports medicine clinic by a doctor of chiropractic over 1 calendar year. Methods A retrospective review of laboratory tests ordered during routine clinical practice as standard screening and diagnostic tests from November 1, 2009, to November 1, 2010 was performed. Data were collected during clinical encounters at one sports medicine clinic and entered into a database for analysis. Descriptive and frequency statistics were used to describe the tests ordered and the frequency of abnormal findings. Results Five hundred and thirty-nine studies were ordered for diagnostic and routine screenings on 137 athlete patients (86 males, 51 females), representing 49 types of tests. Sample sources included blood, urine, skin lesions, and fecal matter. The most commonly ordered tests were complete blood count, comprehensive metabolic panel, serum ferritin, creatine kinase, serum iron and total iron binding capacity, total cortisol, thyroid stimulating hormone, and lipid panels. There were 217 studies (40%) flagged as abnormal by the reporting laboratory. Conclusion This report provides greater insight into the diverse array of laboratory studies ordered over a 1-year period for diagnosis and screening of elite athletes. A high percentage of the results were flagged as abnormal by the laboratory. These findings show that the unique physiology of the elite athlete must be considered when interpreting laboratory findings in this population. PMID:26257590

  12. Global distribution of deep convection reaching tropopause in 1 year GPM observations

    NASA Astrophysics Data System (ADS)

    Liu, Nana; Liu, Chuntao

    2016-04-01

    To characterize and quantify tropopause-reaching deep convection, 1 year of Global Precipitation Mission (GPM) Ku band radar echoes are surveyed in relation to several reference levels derived from the ERA-Interim reanalysis data set. Consistent with the observations of the Tropical Rainfall Measuring Mission over the tropics, the GPM has detected tropopause-reaching deep convection dominantly over tropical land, especially over Panama and Central Africa. At middle and high latitudes, tropopause-reaching convective storms are mainly found over land in the Northern Hemisphere during the summer. Compared to those in the tropics, convective cores at middle and high latitudes have relatively larger sizes at the tropopause, especially those over central North America. The zonal distributions of the occurrences of 15 dBZ and 20 dBZ radar echoes at the tropopause show two comparable maxima, one in the tropics and the other in northern middle-high latitudes. This implies that the convection penetrating the tropopause at northern middle-high latitudes is as frequent as those over the tropics. It is important to understand their role in the vertical transport of trace gases between the troposphere and the stratosphere.

  13. Hippocampal Neuron Number Is Unchanged 1 Year After Fractionated Whole-Brain Irradiation at Middle Age

    SciTech Connect

    Shi Lei Molina, Doris P.; Robbins, Michael E.; Wheeler, Kenneth T.; Brunso-Bechtold, Judy K.

    2008-06-01

    Purpose: To determine whether hippocampal neurons are lost 12 months after middle-aged rats received a fractionated course of whole-brain irradiation (WBI) that is expected to be biologically equivalent to the regimens used clinically in the treatment of brain tumors. Methods and Materials: Twelve-month-old Fischer 344 X Brown Norway male rats were divided into WBI and control (CON) groups (n = 6 per group). Anesthetized WBI rats received 45 Gy of {sup 137}Cs {gamma} rays delivered as 9 5-Gy fractions twice per week for 4.5 weeks. Control rats were anesthetized but not irradiated. Twelve months after WBI completion, all rats were anesthetized and perfused with paraformaldehyde, and hippocampal sections were immunostained with the neuron-specific antibody NeuN. Using unbiased stereology, total neuron number and the volume of the neuronal and neuropil layers were determined in the dentate gyrus, CA3, and CA1 subregions of hippocampus. Results: No differences in tissue integrity or neuron distribution were observed between the WBI and CON groups. Moreover, quantitative analysis demonstrated that neither total neuron number nor the volume of neuronal or neuropil layers differed between the two groups for any subregion. Conclusions: Impairment on a hippocampal-dependent learning and memory test occurs 1 year after fractionated WBI at middle age. The same WBI regimen, however, does not lead to a loss of neurons or a reduction in the volume of hippocampus.

  14. Depression and posttraumatic stress disorder in temporary settlement residents 1 year after the Sichuan earthquake.

    PubMed

    Cheng, Zhang; Ma, Ning; Yang, Lei; Agho, Kingsley; Stevens, Garry; Raphael, Beverley; Cui, Lijun; Liu, Yongqiao; Yan, Baoping; Ma, Hong; Yu, Xin

    2015-03-01

    The authors sought to determine the prevalence and risk factors for major depressive disorder and posttraumatic stress disorder (PTSD) among survivors living in temporary accommodation in the Yongxing settlement in Mianyang city 1 year after the Sichuan earthquake for further interventions. They interviewed 182 residents, using the Structured Clinical Interview for DSM-IV Axis I Disorders and a self-report questionnaire. The 12-month prevalence of depressive disorder and PTSD were 48.9% and 39.6%, respectively. Multivariate analysis indicated that bereaved survivors were 5.51 times (adjusted odds ratio [AOR] = 5.51; 95% confidence interval [CI] =2.14-14.22) more likely to report PTSD and 2.42 times (AOR = 2.42; 95%CI =1.00-5.48) more likely to report depressive disorder than nonbereaved survivors. Older age and receipt of government financial support were significantly associated with 12-month PTSD. Depressive disorder 12 months after the earthquake was associated with receipt of government financial support, pre-earthquake physical illness, single marital status, being currently employed, and Han ethnicity. PMID:23666829

  15. De novo gastric adenocarcinoma 1 year after sleeve gastrectomy in a transplant patient

    PubMed Central

    Masrur, M.; Elli, E.; Gonzalez-Ciccarelli, L.F.; Giulianotti, P.C.

    2016-01-01

    Introduction It has been reported in the literature that upper gastrointestinal malignancies after bariatric surgery are mostly gastro-esophageal, although it is not clear whether bariatric surgery represents a risk factor for the development of esophageal and/or gastric cancer. We report a case of a de novo gastric adenocarcinoma occurring in a transplant patient 1 year after a laparoscopic sleeve gastrectomy. Presentation of case A 44 year-old woman with a BMI of 38 kg/m2, hypertension, type 1 diabetes mellitus, multiple malignancies and a pancreas transplant underwent laparoscopic sleeve gastrectomy. The patient presented with intense dysphagias during the follow up. Studies were performed and the diagnoses of grade 2/3 adenocarcinoma were made. The patient underwent a robotic assisted total gastrectomy with a roux-en-y intracorporeal esophagojejunostomy. The procedure resulted in multiple metastasic lymph nodes, focal and transmural invasions to multiple organs with a tumor free margin resection. The patient presented with a postoperative pleural effusion, with no further complications. Discussion The diagnosis of gastroesophageal cancer after bariatric surgery is usually late since these patients have common upper gastrointestinal symptoms related to the procedure that could delay the diagnosis. De novo gastric cancer after sleeve gastrectomy has only been reported in one instance, in contrast with other bariatric surgery procedures. Conclusions No direct relation has been established between sleeve gastrectomy and the development of gastric cancer. Robotic procedures allow for complex multiorgan resections, while preserving the benefits of minimally invasive surgery. PMID:26774417

  16. Beyond Earth: Weaving Science and Indigenous Culture - A 1-year NSF Planning Grant

    NASA Astrophysics Data System (ADS)

    Young, Timothy; Guy, M.; Baker Big-Back, C.; Froelich, K.

    2011-01-01

    We present results of a 1-year NSF planning grant called Beyond Earth. The project is designed to engage Native American, urban, and rural families in science learning while piloting curriculum development and implementation that incorporates both Native and Western epistemologies. Physical, earth, and space science content is juxtaposed with indigenous culture, stories, language and epistemology in after-school programs and teacher training. Project partners include the Dakota Science Center, Fort Berthold Community College, and Sitting Bull College. The Native American tribes represented in this initiative illustrate partnerships between the Dakota, Lakota, Nakota, Hidatsa, Mandan, and Arikara. Over the past year the primary project deliverables include a culturally responsive curriculum Beyond Earth Moon Module, teacher training workshops, a project website. The curriculum module introduces students to the moon's appearance, phases, and positions in the sky using the Night Sky Planetarium Experience Station to explore core concepts underlying moon phases and eclipses using the interactive Nature Experience Station before engaging in the culminating Mission Challenge in which they apply their knowledge to problem solving situations and projects. The Native Science and Western Science activities developed, planetarium explorations created, and website toolkit utilizations are presented.

  17. Latent Transition Models to Study Women's Changing of Dietary Patterns From Pregnancy to 1 Year Postpartum

    PubMed Central

    Sotres-Alvarez, Daniela; Herring, Amy H.; Siega-Riz, Anna-Maria

    2013-01-01

    Latent class models are useful for classifying subjects by dietary patterns. Our goals were to use latent transition models to identify dietary patterns during pregnancy and postpartum, to estimate the prevalence of these dietary patterns, and to model transition probabilities between dietary patterns as a function of covariates. Women who were enrolled in the Pregnancy, Infection, and Nutrition Study (University of North Carolina, 2000–2005) were followed for 1 year postpartum, and their diets were assessed in the second trimester and at 3 and 12 months postpartum (n = 519, 484, and 374, respectively) by using a food frequency questionnaire. After adjusting for energy intake, parity, smoking status, race, and education, we identified 3 dietary patterns and named them “prudent,” “health conscious Western,” and “Western.” Nulliparas were 2.9 and 2.1 times more likely to be in the “prudent” class than the “health conscious Western” or the “Western” class, respectively. The 3 dietary patterns were very stable, with the “health conscious Western” class being the least stable; the probability for staying in the same class was 0.74 and 0.87 at 3 and 12 months postpartum, respectively. Breastfeeding mothers were more likely than nonbreastfeeding mothers to switch dietary pattern class (P = 0.0286). Except for breastfeeding mothers, most women did not switch dietary patterns from pregnancy to postpartum. PMID:23538942

  18. Surrogate clinical endpoints to predict overall survival in non-small cell lung cancer trials—are we in a new era?

    PubMed Central

    Wang, Xiaofei; Ready, Neal E.

    2015-01-01

    Surrogate endpoints for clinical trials in oncology offer an alternative metric for measuring clinical benefit, allowing for shorter trial duration, smaller patient cohorts, and single arm design. The correlation of surrogate endpoints with overall survival (OS) in therapeutic studies is a central consideration to their validity. The Food and Drug Administration (FDA) recently published an analysis of fourteen clinical trials in advanced non-small cell lung cancer (NSCLC), and discovered a strong association between response rate and progression free survival. Furthermore, a correlation between response rate and OS is demonstrated when analyzing the experimental treatment arm separately, minimizing bias from patient crossover. We also highlight multiple, important considerations when using response as an endpoint in clinical trials involving NSCLC patients. PMID:26798592

  19. Surgery of colorectal cancer lung metastases: analysis of survival, recurrence and re-surgery

    PubMed Central

    Guerrera, Francesco; Mossetti, Claudio; Ceccarelli, Manuela; Bruna, Maria Cristina; Bora, Giulia; Olivetti, Stefania; Lausi, Paolo Olivo; Solidoro, Paolo; Ciccone, Giovannino; Ruffini, Enrico; Oliaro, Alberto

    2016-01-01

    Background Surgery is considered an effective therapeutic option for patients with lung metastasis (MTS) of colorectal cancer (CRC). The purpose of the study was to evaluate efficacy and feasibility of lung metastasectomy in CRC patients and to explore factors of prognostic relevance. Methods This is a retrospective study of patients operated for lung MTS of CRC from 2004 to 2012 in a single Institution. Overall survival (OS) was the primary endpoint. Secondary endpoints were progression free survival (PFS) in resection status R0 and OS in in patients submitted to re-resections. In order to evaluate prognostic factors, a multivariable Cox proportional hazard model was performed. Results One-hundred eighty-eight consecutive patients were included in the final analysis. The median follow-up (FU) was 45 months. The 5-year OS and PFS were 53% (95% CI: 44–60%) and 33% (95% CI: 25–42%), respectively. Two- and 5-year survival after re-resection were 79% (95% CI: 63–89%) and 49% (95% CI: 31–65%), respectively. Multivariate adjusted analysis showed that primary CRC pathological TNM stages (P=0.019), number of resected MTS ≥5 (P=0.009) and lymph nodal involvement (P<0.0001) are independent predictors of poor prognosis. Conclusions Patients operated and re-operated for lung MTS from CRC cancers showed encouraging survival rates. Our results indicated that primary CRC stage, number of MTS and lymph nodal involvement are strong predictive factors. Prognosis after surgery remained comforting up to four resected MTS. Adjuvant chemotherapy seems to have a benefit on survival in patients affected by multiple metastases. Finally, according to the high rate of unidentified lymph node involvement in pre-operative setting, lymph node sampling should be advisable for a correct staging. PMID:27499967

  20. Understanding Cancer: Survivability and Hope

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Survivability and Hope Past Issues / Spring 2007 Table of ... More "Understanding Cancer" Articles Understanding Cancer / Cancer Today / Survivability and Hope / Sam Donaldson: Tips From a Cancer ...

  1. Classification Schemes: Developments and Survival.

    ERIC Educational Resources Information Center

    Pocock, Helen

    1997-01-01

    Discusses the growth, survival and future of library classification schemes. Concludes that to survive, a scheme must constantly update its policies, and readily adapt itself to accommodate growing disciplines and changing terminology. (AEF)

  2. BCR-ABL mutations in chronic myeloid leukemia treated with tyrosine kinase inhibitors and impact on survival.

    PubMed

    Pagnano, Katia Borgia Barbosa; Bendit, Israel; Boquimpani, Carla; De Souza, Carmino Antonio; Miranda, Eliana C M; Zalcberg, Ilana; Larripa, Irene; Nardinelli, Luciana; Silveira, Rosana Antunes; Fogliatto, Laura; Spector, Nelson; Funke, Vaneuza; Pasquini, Ricardo; Hungria, Vania; Chiattone, Carlos Sérgio; Clementino, Nelma; Conchon, Monika; Moiraghi, Elena Beatriz; Lopez, Jose Luis; Pavlovsky, Carolina; Pavlovsky, Miguel A; Cervera, Eduardo E; Meillon, Luis Antonio; Simões, Belinda; Hamerschlak, Nelson; Bozzano, Alicia Helena Magarinos; Mayta, Ernesto; Cortes, Jorge; Bengió, Raquel M

    2015-01-01

    This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients. PMID:26288116

  3. Representation to the accident and emergency department within 1-year of a fractured neck of femur

    PubMed Central

    2011-01-01

    Background The fractured neck of femur (NOF) is a leading cause of morbidity and mortality. The mortality attendant upon such fractures is 10% at 1 month and 30% at one year with a cost to the NHS of £1.4 billion annually. This retrospective study sought to examine rates and prevailing trends in representation to A&E in the year following a NOF fracture in an attempt to identify the leading causes behind the morbidity and mortality associated with this fracture. Methods 1108 patients who suffered a fractured NOF between 1 January 2002 and 31 December 2007 were identified from a University Hospital A&E database. This database was then used to identify those patients who represented within 1-year following the initial fracture. The presenting complaint, provisional diagnosis and the outcome of this presentation were identified at this time. Results 234 patients (21%) returned to A&E on 368 occasions in the year following a hip fracture. 77% (284/368) of these presentations necessitated admission. Falls, infection and fracture were the leading causes of representation. Falls accounted for 20% (57/284) of admissions; 20.7% of patients were admitted because of a fracture, while 56.6% of admissions were for medical ailments of which infection was the chief precipitant (28% (45/161)). Discussion The causes for representation are varied and multifactorial. The results of this study suggest that some of those events or ailments necessitating readmission may be obviated and potentially reduced by interventions that can be instituted during the primary admission and continued following discharge. PMID:22189063

  4. Effectiveness of counselling over 1 year on changes in lifestyle and coronary heart disease risk factors.

    PubMed

    Nisbeth, O; Klausen, K; Andersen, L B

    2000-05-01

    Many have studied the effects of different lifestyles on disease, mortality or risk factors for a disease, but little is known about how behaviour is changed in the population. We studied the need for counselling and its effect on willingness and ability to change lifestyle, and subsequent changes in CHD risk factors. All 152 male employees in a computer company, 25-45 years of age, were invited to participate. Subjects were randomized into an intervention group (I-group) and a control group. The I-group was divided into subgroups based on baseline behaviour and risk factor status. Changes were evaluated after 1 year. After an initial health examination, participants from the I-group were counselled at baseline and after 5 months. Eighty-five (56%) males participated. Twenty-nine were assigned to a control group and 56 to an intervention group (I-group) (dropout = 8). An exercise group (E-group) was advised to exercise aerobically three times/week, a diet group to reduce the intake of saturated fat and increase fish products, and smokers to quit smoking. Forty subjects were recommended one or more behavioural changes and eight had no need. Thirty-four were willing to make behavioural changes. Compared to the control group, the fitness level increased (P < 0.01) and body weight decreased in the I-group (P < 0.05). It may be concluded that individual counselling promotes regular exercise with subsequent improvements in CHD risk factors. The diet- and smoking counselling models were less successful in terms of adherence. PMID:10771366

  5. Cardiovascular Effects of 1 Year of Alagebrium and Endurance Exercise Training in Healthy Older Individuals

    PubMed Central

    Fujimoto, Naoki; Hastings, Jeffrey L.; Carrick-Ranson, Graeme; Shafer, Keri M.; Shibata, Shigeki; Bhella, Paul S.; Abdullah, Shuaib M.; Barkley, Kyler W.; Adams-Huet, Beverley; Boyd, Kara N.; Livingston, Sheryl A.; Palmer, Dean; Levine, Benjamin D.

    2014-01-01

    Background Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise combined with alagebrium would improve LV stiffness in sedentary older humans. Methods and Results Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define LV pressure–volume curves; secondary functional outcomes included cardiopulmonary exercise testing and arterial compliance. A total of 57 of 62 subjects (67±6 years; 37 f/20 m) completed 1 year of intervention followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the slope of LV pressure–volume curve. After intervention, LV mass and end-diastolic volume increased and exercise capacity improved (by ≈8%) only in the exercise groups. Neither LV mass nor exercise capacity was affected by alagebrium. Exercise training had little impact on LV stiffness (training×time effect, P=0.46), whereas alagebrium showed a modest improvement in LV stiffness compared with placebo (medication×time effect, P=0.04). Conclusions Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening. PMID:24130005

  6. Encouraging responses in sexual and relationship violence prevention: what program effects remain 1 year later?

    PubMed

    Moynihan, Mary M; Banyard, Victoria L; Cares, Alison C; Potter, Sharyn J; Williams, Linda M; Stapleton, Jane G

    2015-01-01

    Colleges and universities are high-risk settings for sexual and relationship violence. To address these problems, institutions of higher education have implemented prevention programs, many of which train students as potential bystanders who can step in to help diffuse risky situations, identify and challenge perpetrators, and assist victims. The impact of bystander sexual and relationship violence prevention programs on long-term behavior of bystanders has remained a key unanswered question for those who seek to offer the most effective programs as well as for policy makers. In this study, the researchers experimentally evaluated the effectiveness of the Bringing in the Bystander® in-person program. Participants were 948 1st-year college students of whom 47.8% were women and 85.2% identified as White (15% also identified as Hispanic in a separate question) between the ages of 18 and 24 at two universities (one a rural, primarily residential campus and the other an urban, highly commuter campus) in the northeastern United States. To date, this is the first study to have found positive behavior changes as long-lasting as 1 year following an educational workshop focusing on engaging bystanders in preventing sexual and relationship violence. Even so, many questions remain to be answered about prevention and intervention of this type. More prospective research is needed on bystander-focused prevention of these forms of violence to help understand and better predict the complicated relationships both between and among the attitudes and behaviors related to preventing sexual and relationship violence. In this regard, we make specific recommendations for designing and evaluating programs based on our findings relating to the importance of moderators, especially two key understudied ones, readiness to help and opportunity to intervene. PMID:24850763

  7. Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age.

    PubMed

    Lampe, Christina; Atherton, Andrea; Burton, Barbara K; Descartes, Maria; Giugliani, Roberto; Horovitz, Dafne D G; Kyosen, Sandra O; Magalhães, Tatiana S P C; Martins, Ana Maria; Mendelsohn, Nancy J; Muenzer, Joseph; Smith, Laurie D

    2014-01-01

    Mucopolysaccharidosis (MPS) II, or Hunter syndrome, is a lysosomal storage disease characterized by multi-systemic involvement and a progressive clinical course. Enzyme replacement therapy with idursulfase has been approved in more than 50 countries worldwide; however, safety and efficacy data from clinical studies are currently only available for patients 1.4 years of age and older. Sibling case studies of infants with MPS I, II, and VI who initiated ERT in the first weeks or months of life have reported no new safety concerns and a more favorable clinical course for the sibling treated in infancy than for the later-treated sibling. Here we describe our experiences with a case series of eight MPS II patients for whom idursulfase treatment was initiated at under 1 year of age. The majority of the patients were diagnosed because of a family history of disease. All of the infants displayed abnormalities consistent with MPS II at diagnosis. The youngest age at treatment start was 10 days and the oldest was 6.5 months, with duration of treatment varying between 6 weeks and 5.5 years. No new safety concerns were observed, and none of the patients experienced an infusion-related reaction. All of the patients treated for more than 6 weeks showed improvements and/or stabilization of some somatic manifestations while on treatment. In some cases, caregivers made comparisons with other affected family members and reported that the early-treated patients experienced a less severe clinical course, although a lack of medical records for many family members precluded a rigorous comparison. PMID:24515576

  8. Change in Metabolic Profile after 1-Year Nutritional-Behavioral Intervention in Obese Children

    PubMed Central

    Verduci, Elvira; Lassandro, Carlotta; Giacchero, Roberta; Miniello, Vito Leonardo; Banderali, Giuseppe; Radaelli, Giovanni

    2015-01-01

    Research findings are inconsistent about improvement of specific cardio-metabolic variables after lifestyle intervention in obese children. The aim of this trial was to evaluate the effect of a 1-year intervention, based on normocaloric diet and physical activity, on body mass index (BMI), blood lipid profile, glucose metabolism and metabolic syndrome. Eighty-five obese children aged ≥6 years were analyzed. The BMI z-score was calculated. Fasting blood samples were analyzed for lipids, insulin and glucose. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and insulin resistance was defined as HOMA-IR >3.16. HOMA-β%, quantitative insulin sensitivity check index and triglyceride glucose index were calculated. The metabolic syndrome was defined in accordance with the International Diabetes Federation criteria. At the end of intervention children showed a reduction (mean (95% CI)) in BMI z-score (−0.58 (−0.66; −0.50)), triglycerides (−0.35 (−0.45; −0.25) mmol/L) and triglyceride glucose index (−0.29 (−0.37; −0.21)), and an increase in HDL cholesterol (0.06 (0.01; 0.11) mmol/L). Prevalence of insulin resistance declined from 51.8% to 36.5% and prevalence of metabolic syndrome from 17.1% to 4.9%. Nutritional-behavioral interventions can improve the blood lipid profile and insulin sensitivity in obese children, and possibly provide benefits in terms of metabolic syndrome. PMID:26633492

  9. 1-year prospective real life monitoring of asthma control and quality of life in Italy

    PubMed Central

    2012-01-01

    Objectives The study aimed at prospectively evaluating the evolution of asthma control in Italy, to evaluate the reasons for lack of asthma control, perceived quality of life (QoL) and association with level of asthma control, the impact of pharmacological treatment, the number of exacerbations and the healthcare resource consumption. Methods PRISMA (PRospectIve Study on asthMA control) was an observational study performed in asthmatic patients including a cross-sectional phase and a 12-month prospective phase. Asthma control was assessed with the Asthma Control Test™ (ACT) and QoL was evaluated with EuroQoL-5D questionnaire filled in and collected during 5 clinic visits together with all the other data. Results The prospective phase included 1017 patients with uncontrolled (55.7%) or partly controlled asthma (44.3%). Out of the 739 patients evaluable after 12 months, 22.2% achieved full asthma control (ACT score = 25) and 58.7% reached a good control (ACT score: 20–24). The improvement in asthma control was associated with improved QoL and reduced hospital visits. The main reasons for lack of asthma control were comorbidities, continued exposure to irritants/triggers and poor adherence to therapy. The frequency of exacerbations was lower in patients with controlled asthma. A fixed combination therapy with an inhaled corticosteroid and a long-acting β2 agonist was reported by 77.0% of patients. A better asthma control and improved QoL were achieved with extrafine beclomethasone/formoterol compared to either budesonide/formoterol or fluticasone/salmeterol. Conclusions An improvement in asthma control and QoL can be achieved during a 1-year monitoring in a real life setting. Extrafine beclomethasone/formoterol was associated with significant benefit in terms of asthma control and QoL compared to large-particles combinations. ClinicalTrials.gov number NCT01110460. PMID:23216798

  10. Aerosol source apportionment from 1-year measurements at the CESAR tower in Cabauw, the Netherlands

    NASA Astrophysics Data System (ADS)

    Schlag, Patrick; Kiendler-Scharr, Astrid; Blom, Marcus Johannes; Canonaco, Francesco; Sebastiaan Henzing, Jeroen; Moerman, Marcel; Prévôt, André Stephan Henry; Holzinger, Rupert

    2016-07-01

    Intensive measurements of submicron aerosol particles and their chemical composition were performed with an Aerosol Chemical Speciation Monitor (ACSM) at the Cabauw Experimental Site for Atmospheric Research (CESAR) in Cabauw, the Netherlands, sampling at 5 m height above ground. The campaign lasted nearly 1 year from July 2012 to June 2013 as part of the EU-FP7-ACTRIS project (Q-ACSM Network). Including equivalent black carbon an average particulate mass concentration of 9.50 µg m-3 was obtained during the whole campaign with dominant contributions from ammonium nitrate (45 %), organic aerosol (OA, 29 %), and ammonium sulfate (19 %). There were 12 exceedances of the World Health Organization (WHO) PM2.5 daily mean limit (25 µg m-3) observed at this rural site using PM1 instrumentation only. Ammonium nitrate and OA represented the largest contributors to total particulate matter during periods of exceedance. Source apportionment of OA was performed season-wise by positive matrix factorization (PMF) using the multilinear engine 2 (ME-2) controlled via the source finder (SoFi). Primary organic aerosols were attributed mainly to traffic (8-16 % contribution to total OA, averaged season-wise) and biomass burning (0-23 %). Secondary organic aerosols (SOAs, 61-84 %) dominated the organic fraction during the whole campaign, particularly on days with high mass loadings. A SOA factor which is attributed to humic-like substances (HULIS) was identified as a highly oxidized background aerosol in Cabauw. This shows the importance of atmospheric aging processes for aerosol concentration at this rural site. Due to the large secondary fraction, the reduction of particulate mass at this rural site is challenging on a local scale.

  11. Robot-assisted laparoscopic pyeloplasty: minimum 1-year follow-up

    NASA Astrophysics Data System (ADS)

    Patel, Vipul; Thaly, Rahul; Shah, Ketul

    2007-02-01

    Objectives: To evaluate the feasibility and efficacy of robotic-assisted laparoscopic pyeloplasty. Laparoscopic pyeloplasty has been shown to have a success rate comparable to that of the open surgical approach. However, the steep learning curve has hindered its acceptance into mainstream urologic practice. The introduction of robotic assistance provides advantages that have the potential to facilitate precise dissection and intracorporeal suturing. Methods: A total of 50 patients underwent robotic-assisted laparoscopic dismembered pyeloplasty. A four-trocar technique was used. Most patients were discharged home on day 1, with stent removal at 3 weeks. Patency of the ureteropelvic junction was assessed in all patients with mercaptotriglycylglycine Lasix renograms at 1, 3, 6, 9, and 12 months, then every 6 months for 1 year, and then yearly. Results: Each patient underwent a successful procedure without open conversion or transfusion. The average estimated blood loss was 40 ml. The operative time averaged 122 minutes (range 60 to 330) overall. Crossing vessels were present in 30% of the patients and were preserved in all cases. The time for the anastomosis averaged 20 minutes (range 10 to 100). Intraoperatively, no complications occurred. Postoperatively, the average hospital stay was 1.1 days. The stents were removed at an average of 20 days (range 14 to 28) postoperatively. The average follow-up was 11.7 months; at the last follow-up visit, each patient was doing well. Of the 50 patients, 48 underwent one or more renograms, demonstrating stable renal function, improved drainage, and no evidence of recurrent obstruction. Conclusions: Robotic-assisted laparoscopic pyeloplasty is a feasible technique for ureteropelvic junction reconstruction. The procedure provides a minimally invasive alternative with good short-term results.

  12. A 1-Year Study on the Detection of Human Enteric Viruses in New Caledonia.

    PubMed

    Kaas, Laetitia; Gourinat, Ann-Claire; Urbès, Florence; Langlet, Jérémie

    2016-03-01

    Human enteric viruses occur in high concentrations in wastewater and can contaminate receiving environmental waters. Due to the lack of data on the prevalence of enteric viruses in New Caledonia, the presence and the concentrations of enteric viruses in wastewater and seawater were determined. Untreated wastewater and seawater samples were collected monthly for 1 year from a wastewater treatment plant (WWTP) and from the WWTP's outlet, located directly on a popular recreational beach. Samples were tested for norovirus genogroups I and II (NoV GI and GII), astroviruses (AsV), sapoviruses (SaV), enteroviruses (EV), hepatitis A viruses (HAV), rotaviruses (RoV), human adenoviruses (HAdV) and human polyomaviruses (HPyV). To support these data, faecal samples from cases of gastroenteritis were tested for the first time for NoV and detected in the population. NoV GI, NoV GII, EV, SaV, HAdV and HPyV were detected in all wastewaters, RoV in 75% and AsV in 67%. HAV were not detected in wastewater. Overall, 92% of seawater samples were positive for at least one virus. HPyV were detected most frequently in 92% of samples and at concentrations up to 7.7 × 10(3) genome copies/L. NoV GI, NoV GII, EV, SaV, RoV and HAdV were found in 33, 66, 41, 33, 16 and 66% of seawater samples, respectively. AsV were not detected in seawater. This study reports for the first time the presence of NoV and other enteric viruses in New Caledonia and highlights the year-round presence of enteric viruses in the seawater of a popular beach. PMID:26670603

  13. PM2.5 chemical composition in five European Mediterranean cities: A 1-year study

    NASA Astrophysics Data System (ADS)

    Salameh, Dalia; Detournay, Anais; Pey, Jorge; Pérez, Noemi; Liguori, Francesca; Saraga, Dikaia; Bove, Maria Chiara; Brotto, Paolo; Cassola, Federico; Massabò, Dario; Latella, Aurelio; Pillon, Silvia; Formenton, Gianni; Patti, Salvatore; Armengaud, Alexandre; Piga, Damien; Jaffrezo, Jean Luc; Bartzis, John; Tolis, Evangelos; Prati, Paolo; Querol, Xavier; Wortham, Henri; Marchand, Nicolas

    2015-03-01

    The seasonal and spatial characteristics of PM2.5 and its chemical composition in the Mediterranean Basin have been studied over a 1-year period (2011-2012) in five European Mediterranean cities: Barcelona (BCN), Marseille (MRS), Genoa (GEN), Venice (VEN), and Thessaloniki (THE). During the year under study, PM10 annual mean concentration ranged from 23 to 46 μg m- 3, while the respective PM2.5 ranged from 14 to 37 μg m- 3, with the highest concentrations observed in THE and VEN. Both cities presented an elevated number of exceedances of the PM10 daily limit value, as 32% and 20% of the days exceeded 50 μg m- 3, respectively. Similarly, exceedances of the WHO guidelines for daily PM2.5 concentrations (25 μg m- 3) were also more frequent in THE with 78% of the days during the period, followed by VEN with 39%. The lowest PM levels were measured in GEN. PM2.5 exhibited significant seasonal variability, with much higher winter concentrations for VEN and MRS, in fall for THE and in spring for BCN. PM2.5 chemical composition was markedly different even for similar PM2.5 levels. On annual average, PM2.5 was dominated by OM except in THE. OM contribution was higher in Marseille (42%), while mineral matter was the most abundant constituent in THE (32%). Moreover, PM2.5 relative mean composition during pollution episodes (PM2.5 > 25 μg m- 3) as well as the origins of the exceedances were also investigated. Results outline mainly the effect of NO3- being the most important driver and highlight the non-negligible impact of atmospheric mixing and aging processes during pollution episodes.

  14. Nuclear War Survival Skills

    SciTech Connect

    Kearny, C.H.

    2002-06-24

    The purpose of this book is to provide Americans with information and instructions that will significantly increase their chances of surviving a possible nuclear attack. It brings together field-tested instructions that, if followed by a large fraction of Americans during a crisis that preceded an attack, could save millions of lives. The author is convinced that the vulnerability of our country to nuclear threat or attack must be reduced and that the wide dissemination of the information contained in this book would help achieve that objective of our overall defense strategy.

  15. Nocturnality and species survival.

    PubMed Central

    Daily, G C; Ehrlich, P R

    1996-01-01

    Surveys of butterfly and moth diversity in tropical forest fragments suggest that nocturnality confers a dispersal, and possibly a survival, advantage. The butterfly faunas of smaller fragments were depauperate; in contrast, the species richness of nocturnal moths was similar in all fragments and even in pasture. The lack of correlation between butterfly and moth species richness among fragments (r2 = 0.005) is best explained by movements of moths at night when ambient conditions in forest and pasture are most similar; butterflies face substantial daytime temperature, humidity, and solar radiation barriers. This interpretation is supported by information on birds, beetles, and bats. PMID:8876201

  16. Perceptions Concerning Occupational Survival Skills.

    ERIC Educational Resources Information Center

    Nelson, Robert E.

    This volume presents the reports of a series of interrelated studies which were part of a study that developed curriculum materials for teaching occupational survival skills. The first of six sections, Need for Teaching Occupational Survival Skills and Attitudes, discusses the importance of survival skills and describes twelve general topics which…

  17. SURVIV for survival analysis of mRNA isoform variation.

    PubMed

    Shen, Shihao; Wang, Yuanyuan; Wang, Chengyang; Wu, Ying Nian; Xing, Yi

    2016-01-01

    The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations to clinical outcomes. Here we report a statistical method SURVIV (Survival analysis of mRNA Isoform Variation), designed for identifying mRNA isoform variation associated with patient survival time. A unique feature and major strength of SURVIV is that it models the measurement uncertainty of mRNA isoform ratio in RNA-seq data. Simulation studies suggest that SURVIV outperforms the conventional Cox regression survival analysis, especially for data sets with modest sequencing depth. We applied SURVIV to TCGA RNA-seq data of invasive ductal carcinoma as well as five additional cancer types. Alternative splicing-based survival predictors consistently outperform gene expression-based survival predictors, and the integration of clinical, gene expression and alternative splicing profiles leads to the best survival prediction. We anticipate that SURVIV will have broad utilities for analysing diverse types of mRNA isoform variation in large-scale clinical RNA-seq projects. PMID:27279334

  18. SURVIV for survival analysis of mRNA isoform variation

    PubMed Central

    Shen, Shihao; Wang, Yuanyuan; Wang, Chengyang; Wu, Ying Nian; Xing, Yi

    2016-01-01

    The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations to clinical outcomes. Here we report a statistical method SURVIV (Survival analysis of mRNA Isoform Variation), designed for identifying mRNA isoform variation associated with patient survival time. A unique feature and major strength of SURVIV is that it models the measurement uncertainty of mRNA isoform ratio in RNA-seq data. Simulation studies suggest that SURVIV outperforms the conventional Cox regression survival analysis, especially for data sets with modest sequencing depth. We applied SURVIV to TCGA RNA-seq data of invasive ductal carcinoma as well as five additional cancer types. Alternative splicing-based survival predictors consistently outperform gene expression-based survival predictors, and the integration of clinical, gene expression and alternative splicing profiles leads to the best survival prediction. We anticipate that SURVIV will have broad utilities for analysing diverse types of mRNA isoform variation in large-scale clinical RNA-seq projects. PMID:27279334

  19. Epidemiologic study on survival of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    PubMed Central

    Mauro, Michael J.; Martinelli, Giovanni; Kim, Dong-Wook; Soverini, Simona; Müller, Martin C.; Hochhaus, Andreas; Cortes, Jorge; Chuah, Charles; Dufva, Inge H.; Apperley, Jane F.; Yagasaki, Fumiharu; Pearson, Jay D.; Peter, Senaka; Sanz Rodriguez, Cesar; Preudhomme, Claude; Giles, Francis; Goldman, John M.; Zhou, Wei

    2009-01-01

    The BCR–ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and Philadelphia chromosome—positive (Ph)+ acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation detection was 54 years; 57% cases were men. Median time between TKI treatment initiation and T315I mutation detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and Ph+ ALL patients. After T315I mutation detection, second-generation TKIs were used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK-0457 in 11%, stem cell transplantation in 17%, and interferon-α in 6% of cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0, and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5 months, respectively, for CP, AP, BP, and Ph+ ALL patients. These results confirm that survival of patients harboring a T315I mutation is dependent on disease phase at the time of mutation detection. PMID:19843886

  20. IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy.

    PubMed

    Minniti, Giuseppe; Scaringi, Claudia; Arcella, Antonella; Lanzetta, Gaetano; Di Stefano, Domenica; Scarpino, Stefania; Bozzao, Alessandro; Pace, Andrea; Villani, Veronica; Salvati, Maurizio; Esposito, Vincenzo; Giangaspero, Felice; Enrici, Riccardo Maurizi

    2014-06-01

    Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8-63.2) and 38% (95 % CI, 25.7-50.7%), and median and 5-year progression-free survival rates were 36 months (95% CI, 28.5-44.0) and 22 % (95 % CI, 10-34%), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60% of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age < 50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated. PMID:24748470

  1. SurvNet: a web server for identifying network-based biomarkers that most correlate with patient survival data.

    PubMed

    Li, Jun; Roebuck, Paul; Grünewald, Stefan; Liang, Han

    2012-07-01

    An important task in biomedical research is identifying biomarkers that correlate with patient clinical data, and these biomarkers then provide a critical foundation for the diagnosis and treatment of disease. Conventionally, such an analysis is based on individual genes, but the results are often noisy and difficult to interpret. Using a biological network as the searching platform, network-based biomarkers are expected to be more robust and provide deep insights into the molecular mechanisms of disease. We have developed a novel bioinformatics web server for identifying network-based biomarkers that most correlate with patient survival data, SurvNet. The web server takes three input files: one biological network file, representing a gene regulatory or protein interaction network; one molecular profiling file, containing any type of gene- or protein-centred high-throughput biological data (e.g. microarray expression data or DNA methylation data); and one patient survival data file (e.g. patients' progression-free survival data). Given user-defined parameters, SurvNet will automatically search for subnetworks that most correlate with the observed patient survival data. As the output, SurvNet will generate a list of network biomarkers and display them through a user-friendly interface. SurvNet can be accessed at http://bioinformatics.mdanderson.org/main/SurvNet. PMID:22570412

  2. Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials

    PubMed Central

    Flaherty, Keith T; Hennig, Michael; Lee, Sandra J; Ascierto, Paolo A; Dummer, Reinhard; Eggermont, Alexander M M; Hauschild, Axel; Kefford, Richard; Kirkwood, John M; Long, Georgina V; Lorigan, Paul; Mackensen, Andreas; McArthur, Grant; O'Day, Steven; Patel, Poulam M; Robert, Caroline; Schadendorf, Dirk

    2015-01-01

    Summary Background Recent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials. Methods We systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose. Findings After screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0.71 (95% CI 0.29–0.90) with a random-effects assumption, 0.85 (0.59–0.95) with a fixed-effects assumption, and 0.89 (0.68–0.97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0.96 (0.81–0.99), which decreased to 0.93 (0.74–0.98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0.55, 0.03–0.84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0.85 (0.51–0.96). Interpretation PFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of

  3. Postfledging survival of European starlings

    USGS Publications Warehouse

    Krementz, D.G.; Nichols, J.D.; Hines, J.E.

    1989-01-01

    We tested the hypotheses that mass at fledging and fledge date within the breeding season affect postfledging survival in European Starlings (Sturnus vulgaris). Nestlings were weighed on day 18 after hatch and tagged with individually identifiable patagial tags. Fledge date was recorded. Marked fledglings were resighted during weekly two-day intensive observation periods for 9 weeks postfledging. Post-fledging survival and sighting probabilities were estimated for each of four groups (early or late fledging by heavy or light fledging mass). Body mass was related to post-fledging survival for birds that fledged early. Results were not clear-cut for relative fledge date, although there was weak evidence that this also influenced survival. Highest survival probability estimates occurred in the EARLY-HEAVY group, while the lowest survival estimate occurred in the LATE-LIGHT group. Sighting probabilities differed significantly among groups, emphasizing the need to estimate and compare survival using models which explicitly incorporate sighting probabilities.

  4. Survival After Solid Cancers in Antithrombotic Trials.

    PubMed

    Serebruany, Victor L; Tomek, Ales; Kim, Moo Hyun

    2015-09-15

    The impact of antithrombotics on cancer is currently under intense investigation because of the excess of solid cancers in trials after thienopyridines such as TRITON (prasugrel), DAPT (prasugrel and clopidogrel), PAR-1 thrombin antagonist in TRACER (vorapaxar), pyrimidines in PEGASUS (ticagrelor), and in APPRAISE-2 after apixaban. However, whether patient survival after solid cancer (SASC) in antithrombotic trials may be affected is unknown. We matched the 1-year SASC rate in antithrombotic trials reported by Food and Drug Administration with the census averages in Surveillance, Epidemiology, and End Results (SEER) Program by the US National Cancer Institute and World Health Organization (WHO) surveys. The Food and Drug Administration provided the SASC data for 3 trials with similar cancer survival of about 70% for the first year of follow-up in TRITON, APPRAISE-2, and ARISTOTEL. Adjusted cancers in TRITON with SEER (odds ratio 0.92; 95% confidence interval 0.53 to 1.59, p = 0.4351) and WHO (odds ratio 0.99; 95% confidence interval 0.57 to 1.7, p = 1.00) revealed very close if not identical SASC rates in antithrombotic trials compared to epidemiologic census estimates. In conclusion, SASC rates in patients enrolled in antithrombotic trials do not differ from SEER or World Health Organization averages. PMID:26189037

  5. TLR4/TIRAP polymorphisms are associated with progression and survival of patients with symptomatic myeloma.

    PubMed

    Bagratuni, Tina; Terpos, Evangelos; Eleutherakis-Papaiakovou, Evangelos; Kalapanida, Despoina; Gavriatopoulou, Maria; Migkou, Magdalini; Liacos, Christine-Ivy; Tasidou, Anna; Matsouka, Charis; Mparmparousi, Despoina; Dimopoulos, Meletios A; Kastritis, Efstathios

    2016-01-01

    Myeloma cells thrive in an environment of sustained inflammation, which impacts the development and evolution of the disease, as well as drug resistance. We evaluated the impact of genetic polymorphisms in the Toll-like receptor 4 (TLR4) pathway, which have been implicated in different inflammatory responses in the outcomes of patients with symptomatic multiple myeloma (MM) who have received contemporary therapies. We found that the presence of single nucleotide polymorphisms (SNPs) in both the TLR4 and toll/interleukin-1 receptor (TIR)-associated protein (TIRAP) genes was associated with lower response to primary therapy mainly for patients who received immunomodulatory drugs but not in patients treated with bortezomib-based therapies. Furthermore, TIRAP SNP was associated with a significantly shorter progression-free survival and overall survival, independently of other prognostic factors, such as age, transplant, International Staging System stage, lactate dehydrogenase and cytogenetics. This is the first study to demonstrate the effect of SNPs in TLR4/TIRAP in MM. Our data indicate that genetic variability in the immune system may be associated with different responses to antimyeloma therapies and may be a critical component affecting the natural history of the disease, providing the basis for further investigation of the role of these pathways in myeloma. PMID:26564000

  6. Survival in patients with acute myeloblastic leukemia in Germany and the United States: Major differences in survival in young adults.

    PubMed

    Pulte, Dianne; Jansen, Lina; Castro, Felipe A; Krilaviciute, Agne; Katalinic, Alexander; Barnes, Benjamin; Ressing, Meike; Holleczek, Bernd; Luttmann, Sabine; Brenner, Hermann

    2016-09-15

    Previous epidemiologic studies on AML have been limited by the rarity of the disease. Here, we present population level data on survival of patients with AML in Germany and the United States (US). Data were extracted from 11 population-based cancer registries in Germany and the Surveillance, Epidemiology, and End Results (SEER13) database in the US. Patients diagnosed with AML in 1997-2011 were included. Period analysis was used to estimate 5-year relative survival (RS) and trends in survival in the early 21st century. Overall 5-year age-adjusted RS for patients with AML in 2007-2011 was greater in Germany than in the US at 22.8% and 18.8%, respectively. Five-year RS was higher in Germany than in the US at all ages, with particularly large differences at ages 15-24 for whom 5-year RS was 64.3% in Germany and 55.0% in the US and 35-44, with 5-year RS estimates of 61.8% in Germany and 46.6% in the US. Most of the difference in 5-year RS was due to higher 1-year RS, with overall 1-year RS estimates of 47.0% in Germany and 38.5% in the US. A small increase in RS was observed between 2003-2005 and 2009-2011 in both countries, but no increase in survival was observed in either country for ages 75+. To our knowledge, this is the first detailed description of AML survival in Germany. Comparison to the US suggests that further analysis into risk factors for poor outcomes in AML in the US may be useful in improving survival. PMID:27176899

  7. Survival benefit and safety of the combinations of FOLFOXIRI ± bevacizumab versus the combinations of FOLFIRI ± bevacizumab as first-line treatment for unresectable metastatic colorectal cancer: a meta-analysis

    PubMed Central

    Xu, Wei; Kuang, Meng; Gong, Yang; Cao, Chunxiang; Chen, Jinfei; Tang, Cuiju

    2016-01-01

    Background The survival of patients with metastatic colorectal cancer (mCRC) could be improved with exposure to three active drugs, irinotecan, fluorouracil/leucovorin, and oxaliplatin, irrespective of their sequence. However, only 50%–80% of patients can be exposed to all the three drugs in a sequential strategy with two-drug combinations. We carried out this systematic assessment to compare the survival benefit and safety of FOLFOXIRI (irinotecan, fluorouracil/leucovorin, and oxaliplatin) ± bevacizumab (with or without bevacizumab) versus FOLFIRI (irinotecan and fluorouracil/leucovorin) ± bevacizumab (with or without bevacizumab) as first-line treatment for unresectable mCRC. Methods PubMed and EMBASE were searched for original articles written in English and published before December 2015. A total of 1,035 patients from three randomized controlled trials were included. Results Our results demonstrated that overall survival (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.73–0.97), progression-free survival (HR, 0.69; 95% CI, 0.59–0.81), and overall response rate (odds ratio, 1.96; 95% CI, 1.28–2.98) were significantly improved in the FOLFOXIRI ± bevacizumab arm compared to the FOLFIRI ± bevacizumab arm. Significantly higher incidences of neutropenia, anemia, diarrhea, stomatitis, and neuropathy were observed in the FOLFOXIRI ± bevacizumab arm. Conclusion Current evidence shows that the combination of FOLFOXIRI ± bevacizumab significantly improves the overall survival, progression-free survival, and overall response rate of patients with mCRC, with an increased but manageable toxicity, compared with the combinations of FOLFIRI ± bevacizumab. The combination of FOLFOXIRI ± bevacizumab should be considered as a treatment option for these patients under the premise of reasonable selection of target population. PMID:27536147

  8. Racial Differences in the Impact of Comorbidities on Survival Among Elderly Men With Prostate Cancer

    PubMed Central

    Putt, Mary; Long, Judith A.; Montagnet, Chantal; Silber, Jeffrey H.; Chang, Virginia W.; Liao, Kaijun; Schwartz, J. Sanford; Pollack, Craig Evan; Wong, Yu-Ning; Armstrong, Katrina

    2009-01-01

    This study investigates differences in the effects of comorbidities on survival in Medicare beneficiaries with prostate cancer. Medicare data were used to assemble a cohort of 65- to 76-year-old Black (n = 6,402) and White (n = 47,458) men with incident localized prostate cancer in 1999 who survived1 year postdiagnosis. Comorbidities were more prevalent among Blacks than among Whites. For both races, greater comorbidity was associated with decreasing survival rates; however, the effect among Blacks was smaller than in Whites. After adjusting for age, socioeconomic status, and community characteristics, the association between increasing comorbidities and survival remained weaker for Blacks than for Whites, and racial disparity in survival decreased with increasing number of comorbidities. Differential effects of comorbidities on survival were also evident when examining different classes of comorbid conditions. Adjusting for treatment had little impact on these results, despite variation in the racial difference in receipt of prostatectomy with differing comorbidity levels. PMID:19357389

  9. Process control for survival

    SciTech Connect

    Yocom, J.A.

    1991-06-01

    Increasing competition for a decreasing market mandates that the success of a company be determined by the manner in which it embraces quality. Statistical Process Control (SPC) is the most efficient means of dramatically improving quality and is essential to survival in the emerging electronic marketplace. During the three years that industry practitioners assembled to write IPC-PC-90, General Requirements for the Implementation of statistical Process Control, many heated discussions ensued about the actual definition of SPC. Some people view SPC as the application of Control Chart methods, others view it as the use of Statistical Experimental Design. Both are in some ways wrong and are limiting the scope of application. Those companies that have successfully applied SPC view it as a philosophy of statistical principles that will reduce variation in every phase of their business. 2 figs.

  10. Development of 1-year-old computational phantom and calculation of organ doses during CT scans using Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Pan, Yuxi; Qiu, Rui; Gao, Linfeng; Ge, Chaoyong; Zheng, Junzheng; Xie, Wenzhang; Li, Junli

    2014-09-01

    With the rapidly growing number of CT examinations, the consequential radiation risk has aroused more and more attention. The average dose in each organ during CT scans can only be obtained by using Monte Carlo simulation with computational phantoms. Since children tend to have higher radiation sensitivity than adults, the radiation dose of pediatric CT examinations requires special attention and needs to be assessed accurately. So far, studies on organ doses from CT exposures for pediatric patients are still limited. In this work, a 1-year-old computational phantom was constructed. The body contour was obtained from the CT images of a 1-year-old physical phantom and the internal organs were deformed from an existing Chinese reference adult phantom. To ensure the organ locations in the 1-year-old computational phantom were consistent with those of the physical phantom, the organ locations in 1-year-old computational phantom were manually adjusted one by one, and the organ masses were adjusted to the corresponding Chinese reference values. Moreover, a CT scanner model was developed using the Monte Carlo technique and the 1-year-old computational phantom was applied to estimate organ doses derived from simulated CT exposures. As a result, a database including doses to 36 organs and tissues from 47 single axial scans was built. It has been verified by calculation that doses of axial scans are close to those of helical scans; therefore, this database could be applied to helical scans as well. Organ doses were calculated using the database and compared with those obtained from the measurements made in the physical phantom for helical scans. The differences between simulation and measurement were less than 25% for all organs. The result shows that the 1-year-old phantom developed in this work can be used to calculate organ doses in CT exposures, and the dose database provides a method for the estimation of 1-year-old patient doses in a variety of CT examinations.

  11. The value of surrogate endpoints for predicting real-world survival across five cancer types.

    PubMed

    Shafrin, Jason; Brookmeyer, Ron; Peneva, Desi; Park, Jinhee; Zhang, Jie; Figlin, Robert A; Lakdawalla, Darius N

    2016-04-01

    Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints - progression-free survival (PFS) and time to progression (TTP) - to predict real-world OS across five cancers. Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan-Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991-2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R(2) from linear regressions. Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P = 0.026). Among all real-world patients using sample treatments (N = 309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P = 0.194). Results were qualitatively similar using median absolute prediction error and R(2) metrics. Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone. PMID:26743800

  12. Do Increased Doses to Stem-Cell Niches during Radiation Therapy Improve Glioblastoma Survival?

    PubMed Central

    Adeberg, Sebastian; Harrabi, Semi Ben; Mohr, Angela; Rieber, Juliane; Rieken, Stefan; Debus, Juergen

    2016-01-01

    Background and Purpose. The reasons for the inevitable glioblastoma recurrence are yet understood. However, recent data suggest that tumor cancer stem cells (CSCs) in the stem-cell niches, with self-renewing capacities, might be responsible for tumor initiation, propagation, and recurrence. We aimed to analyze the effect of higher radiation doses to the stem-cell niches on progression-free survival (PFS) and overall survival (OS) in glioblastoma patients. Materials and Methods. Sixty-five patients with primary glioblastoma treated with radiation therapy were included in this retrospective analysis. The SVZ and DG were segmented on treatment planning magnetic resonance imaging, and the dose distributions to the structures were calculated. The relationship of dosimetry data and survival was evaluated using the Cox regression analysis. Results. Conventionally fractionated patients (n = 54) who received higher doses (Dmean ≥ 40 Gy) to the IL SVZ showed improved PFS (8.5 versus 5.2 months; p = 0.013). Furthermore, higher doses (Dmean ≥ 30 Gy) to the CL SVZ were associated with increased PFS (10.1 versus 6.9 months; p = 0.025). Conclusion. Moderate higher IL SVZ doses (≥40 Gy) and CL SVZ doses (≥30 Gy) are associated with improved PFS. Higher doses to the DG, the second stem-cell niche, did not influence the survival. Targeting the potential cancer stem cells in the SVZ might be a promising treatment approach for glioblastoma and should be addressed in a prospective randomized trial. PMID:27429623

  13. A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype.

    PubMed

    Valente, Kari; Blackham, Aaron U; Levine, Edward; Russell, Greg; Votanopoulos, Konstantinos I; Stewart, John H; Shen, Perry; Geisinger, Kim R; Sirintrapun, Sahussapont J

    2016-09-01

    Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype. PMID:27438989

  14. The Lymphocyte-Monocyte Ratio Predicts Patient Survival and Aggressiveness of Ovarian Cancer

    PubMed Central

    Eo, Wan Kyu; Chang, Hye Jung; Kwon, Sang Hoon; Koh, Suk Bong; Kim, Young Ok; Ji, Yong Il; Kim, Hong-Bae; Lee, Ji Young; Suh, Dong Soo; Kim, Ki Hyung; Chang, Ik Jin; Kim, Heung Yeol; Chang, Suk Choo

    2016-01-01

    Objective: To measure the prognostic value of the lymphocyte-monocyte ratio (LMR) in patients with epithelial ovarian cancer (EOC). Methods: We retrospectively examined the LMR as a prognosticator in a cohort of 234 patients with EOC who underwent surgical resection. Patients were categorized into two different groups based on the LMR (LMR-low and LMR-high) using cut-off values determined by receiver operating characteristic (ROC) curve analysis. The objective of the study was to assess the effect of the LMR on progression-free survival (PFS) and overall survival (OS), and to validate the LMR as an independent predictor of survival. Results: Using the data collected from the whole cohort, the optimized LMR cut-off value selected on the ROC curve was 2.07 for both PFS and OS. The LMR-low and LMR-high groups included 48 (20.5%) and 186 patients (79.5%), respectively. The 5-year PFS rates in the LMR-low and LMR-high groups were 40.0 and 62.5% (P < 0.0001), respectively, and the 5-year OS rates in these two groups were 42.2 and 67.2% (P < 0.0001), respectively. On multivariate analysis, we identified age, International Federation of Gynecology and Obstetrics (FIGO) stage, and cancer antigen 125 levels to be the strongest valuable prognostic factors affecting PFS (P = 0.0421, P = 0.0012, and P = 0.0313, respectively) and age, FIGO stage, and the LMR as the most valuable prognostic factors predicting OS (P = 0.0064, P = 0.0029, and P = 0.0293, respectively). Conclusion: The LMR is an independent prognostic factor affecting the survival of patients with EOC. PMID:26918042

  15. Plasmodium vivax Sub-Patent Infections after Radical Treatment Are Common in Peruvian Patients: Results of a 1-Year Prospective Cohort Study

    PubMed Central

    Delgado, Christopher; Gamboa, Dionicia; Grande, Tanilu; Rodriguez, Hugo; Llanos-Cuentas, Alejandro; Anné, Jozef; D'Alessandro, Umberto; Erhart, Annette

    2011-01-01

    Background There is an increasing body of literature reporting treatment failure of the currently recommended radical treatment of Plasmodium vivax infections. As P. vivax is the main malaria species outside the African continent, emerging tolerance to its radical treatment regime could have major consequences in countries like Peru, where 80% of malaria cases are due to P. vivax. Here we describe the results of a 1-year longitudinal follow up of 51 confirmed P. vivax patients living around Iquitos, Peruvian Amazon, and treated according to the Peruvian national guidelines. Methodology Each month a blood sample for microscopy and later genotyping was systematically collected. Recent exposure to infection was estimated by detecting antibodies against the P. vivax circumsporozoite protein (CSP) and all PCR confirmed P. vivax infections were genotyped with 16 polymorphic microsatellites. Results During a 1-year period, 84 recurrent infections, 22 positive also by microscopy, were identified, with a median survival time to first recurrent infection of 203 days. Most of them (71%) were asymptomatic; in 13 patients the infection persisted undetected by microscopy for several consecutive months. The genotype of mostly recurrent infections differed from that at day 0 while fewer differences were seen between the recurrent infections. The average expected heterozygosity was 0.56. There was strong linkage disequilibrium (IAs = 0.29, p<1.10−4) that remained also when analyzing only the unique haplotypes, suggesting common inbreeding. Conclusion In Peru, the P. vivax recurrent infections were common and displayed a high turnover of parasite genotypes compared to day 0. Plasmodium vivax patients, even when treated according to the national guidelines, may still represent an important parasite reservoir that can maintain transmission. Any elimination effort should consider such a hidden reservoir. PMID:21297986

  16. Survival by Stage of Soft Tissue Sarcoma

    MedlinePlus

    ... Next Topic How are soft tissue sarcomas treated? Survival by stage of soft tissue sarcoma Survival rates ... observed, not relative survival): Stage 5-year observed survival rate I 90% II 81% III 56% IV ...

  17. Surviving a Suicide Attempt

    PubMed Central

    Al-Harrasi, Ahmed; Al Maqbali, Mandhar; Al-Sinawi, Hamed

    2016-01-01

    Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors) and protective factors (like religious affiliation and family support). All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor. PMID:27602193

  18. Determination of Survivable Fires

    NASA Technical Reports Server (NTRS)

    Dietrich, D. L.; Niehaus, J. E.; Ruff, G. A.; Urban, D. L.; Takahashi, F.; Easton, J. W.; Abbott, A. A.; Graf, J. C.

    2012-01-01

    At NASA, there exists no standardized design or testing protocol for spacecraft fire suppression systems (either handheld or total flooding designs). An extinguisher's efficacy in safely suppressing any reasonable or conceivable fire is the primary benchmark. That concept, however, leads to the question of what a reasonable or conceivable fire is. While there exists the temptation to over-size' the fire extinguisher, weight and volume considerations on spacecraft will always (justifiably) push for the minimum size extinguisher required. This paper attempts to address the question of extinguisher size by examining how large a fire a crew member could successfully survive and extinguish in the confines of a spacecraft. The hazards to the crew and equipment during an accidental fire include excessive pressure rise resulting in a catastrophic rupture of the vehicle skin, excessive temperatures that burn or incapacitate the crew (due to hyperthermia), carbon dioxide build-up or other accumulation of other combustion products (e.g. carbon monoxide). Estimates of these quantities are determined as a function of fire size and mass of material burned. This then becomes the basis for determining the maximum size of a target fire for future fire extinguisher testing.

  19. Surviving a Suicide Attempt.

    PubMed

    Al-Harrasi, Ahmed; Al Maqbali, Mandhar; Al-Sinawi, Hamed

    2016-09-01

    Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors) and protective factors (like religious affiliation and family support). All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor. PMID:27602193

  20. Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

    PubMed

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-04-01

    The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease.Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan.A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995-2003 vs 2004-2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival.Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%-16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol.By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  1. Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

    PubMed Central

    Heist, Rebecca S.; Duda, Dan G.; Sahani, Dushyant V.; Ancukiewicz, Marek; Fidias, Panos; Sequist, Lecia V.; Temel, Jennifer S.; Shaw, Alice T.; Pennell, Nathan A.; Neal, Joel W.; Gandhi, Leena; Lynch, Thomas J.; Engelman, Jeffrey A.; Jain, Rakesh K.

    2015-01-01

    Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non–small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment—while reducing blood flow, volume, and permeability in the overall population—may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy. PMID:25605928

  2. A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma

    PubMed Central

    TREGGIARI, Elisabetta; GRANT, Jessica Pauline; NORTH, Susan Margaret

    2016-01-01

    A xenogeneic DNA vaccination has been licensed for use in dogs with locally controlled stage II and III oral malignant melanoma (OMM). At present, there are limited outcome data for dogs with OMM treated with surgery and immunotherapy. The aim of this study is to retrospectively review the outcome and survival of 32 dogs affected by OMM that were treated with a combination of surgery and the xenogeneic DNA vaccination (with the addition of radiotherapy in some cases) and to determine the influence of surgical margins and delay in receiving vaccination. The overall median survival time (MST) was 335 days (95% CI: 301–540 days), and the overall median progression-free survival (PFS) was 160 days (mean 182 days, 95% CI: 132–232 days). Stage, completeness of surgical margins and delay in administration of the vaccine did not appear to statistically influence survival or PFS, although these results may reflect the low statistical power of the study due to small numbers. Further studies are required to assess whether the addition of any adjuvant treatment to surgery, including immunotherapy, is able to significantly prolong survival in cases of canine oral melanoma. PMID:26781703

  3. Prolonged survival in adult neurofibromatosis type I patients with recurrent high-grade gliomas treated with bevacizumab.

    PubMed

    Theeler, Brett J; Ellezam, Benjamin; Yust-Katz, Shlomit; Slopis, John M; Loghin, Monica E; de Groot, John F

    2014-08-01

    Astrocytic tumors, especially optic pathway pilocytic astrocytomas, are common in pediatric NF1 patients. High-grade gliomas (HGGs) appear to be rare in adult and pediatric NF1 patients. This is a series of five consecutive, adult NF1 patients with recurrent HGGs treated at The University of Texas MD Anderson Cancer Center. Four patients met consensus clinical criteria for NF1 and one patient had presumed segmental NF1. Three patients had glioblastomas, one gliosarcoma, and one progressive, enhancing optic pathway glioma which was not biopsied. Two tumors had molecular testing performed; both were IDH wild type and activating oncogene mutations (1 BRAFV600E and 1 PIK3CA mutation) were found in these tumors. All five patients received bevacizumab-containing regimens at tumor recurrence. The median number of 4-week cycles of bevacizumab was 20. All five patients experienced prolonged post-recurrence survival following bevacizumab treatment ranging from ten to 72 months. The median overall survival from HGG diagnosis was 72.6 months with three patients alive and progression free at last follow-up. Three out of five patients developed vascular complications leading to bevacizumab discontinuation. In this case series, adult NF1 patients with recurrent HGGs had prolonged, post-recurrence survival after treatment with bevacizumab-containing regimens. Based on these results, further study of antiangiogenic therapy in NF1 patients with HGGs and bevacizumab-response in sporadic HGG patients with NF1-mutated tumors is warranted. PMID:24859329

  4. Time-course pattern of blood 25-hydroxycholecalciferol is a significant predictor of survival outcome in metastatic colorectal cancer: a clinical practice-based study.

    PubMed

    Obermannova, R; Dusek, L; Greplova, K; Jarkovsky, J; Sterba, J; Vyzula, R; Demlova, R; Zdrazilova-Dubska, L; Valik, D

    2015-01-01

    Vitamin D deficiency has been implicated in the epidemiology of common malignancies including colorectal cancer. We studied consecutive blood levels of 25-hydroxycholecalciferol (25-OHD) in relation to other clinical and laboratory variables in metastatic colorectal cancer patients to ascertain whether their variations may be prognostic or predictive parameters of survival outcomes. Eighty four patients treated with first-line oxaliplatin-based chemotherapy with or without bevacizumab were included. The patients were enrolled on the intent-to-treat basis considering their performance status, comorbidities and laboratory parameters to be medically apt for intensive chemotherapy. Overall survival and progression-free survival were selected as the primary outcomes. Progression free survival and overall survival medians were 15.4 months and 41.2 months, respectively. The cut-off levels of 40 nmol/l for 25-OHD and 11 µg/l for first CEA were identified to be clinical decision levels stratifying patients to the respective prognostic groups. We found that the most consistent outcome predictors were i) any patient surgery, ii) CEA and, independently, iii) time-related blood levels of 25-OHD. We confirmed fundamental and consistent vitamin D deficiency in metastatic colorectal cancer. We demonstrated that all patients with at least one blood level above 40 nmol/l versus all below this cut-off showed profound differences in their disease outcomes. The primary disease stage or time to metastatic stage did not influence the predictive power of blood 25-OHD levels, implying that the time-course pattern of 25-OHD but not the first single measurement may be an independent prognostic factor. PMID:26458311

  5. Survival of Planetary Systems

    NASA Astrophysics Data System (ADS)

    Ward, William R.

    1996-06-01

    Recent low frequency results from attempts to detect Jupiter-sized planets around nearby stars have raised a question as to whether such objects are all that common. In the over 200 stars observed so far, the yield has been 3%. And, the close orbit (0.05 AU) of the nearly Jupiter-sized object around Peg 51 places the object in an environment where the current paradigm of planetary formation would not predict planets to form at all. Other newly discovered candidates, such a Vir 70 and HR3522, also have suspiciously small semi-major axes for gas giants. Of course, the low yield may be strongly influenced by selection effects since massive planets close to their primaries are more easily detected. Nevertheless, given the results to date, it is natural to wonder whether a planetary system like ours is such a natural outgrowth of a circumplantary disk. In particular, could there be forces absent from the existing paradigm that tend to destroy a planetary system once formed? We point out that strong gravitational interactions (i.e., disk tides) between a newly formed protoplanet and its precursor disk give rise to a net torque that drains angular momentum from the protoplanet's orbit. As a result, protoplanetary objects suffer orbital decay as the disk attempts to destroy the very system it spawns. Strong interaction (type I) leads to gap formation and co-evolution with the disk; weak inter- action (type II) leads to drift relative to the disk and in some cases, a much more rapid decay. Survival of a planetary system may be a comparatively uncommon outcome. Newly discovered planets such as Peg 51b may be evidence of such large-scale orbit migration due to disk tidal torques (i.e., Lin et al., 1996).

  6. Predicting Survival in ARDS.

    PubMed

    Karnik, Niteen D; Gupta, Anish V

    2015-11-01

    Acute respiratory distress syndrome (ARDS) is a fulminant clinical disorder of varied etiology, characterized by diffuse lung injury and severe hypoxemia. It is a leading cause of ICU admission and the associated high mortality has sparked a lot of research on etiology, outcome, scoring systems, mortality predictors, biomarkers including inflammatory cytokines and even genomics in ARDS. The previously used AECC (American European Consensus Conference) definition (1994) of ARDS was replaced by the recent Berlin definition (2012) so as to improve its validity and reliability.1,2 This would not only standardize patient enrollment into clinical trials but also help implement the results of these trials into clinical practice. Although various studies have shown a reduction in mortality due to ARDS, it has been largely attributed to the general improvement in critical care and the use of lung protection ventilation strategies.3-6 Hence focus on the etiology, co-morbidities, risk factors, complications and mortality predictors, is the need of the hour so as to improve survival. ARDS can occur secondary to multiple causes i.e. either due to direct lung involvement (pneumonia, lung contusion etc) or indirect alveolar damage by inflammatory cytokines (sepsis, trauma, burns, pancreatitis etc.). The causes of ARDS in tropical countries are varied with seasonal variation. Acute febrile illnesses (AFI) like malaria, leptospirosis and dengue usually predominate in the monsoons while H1N1 infection and pneumonias typically peak in the colder winter months. However, malaria, dengue and H1N1 have a potential to be perennial. PMID:27608777

  7. Greater nutrition knowledge is associated with lower 1-year postpartum weight retention in low-income women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to assess nutrition knowledge during early and late postpartum in a sample of low-income and minority women, and to determine if that knowledge had any relationship to weight retention at 1-year postpartum. A questionnaire was developed and validated in a sample of 151 ...

  8. Decrease in Television Viewing Predicts Lower Body Mass Index at 1-Year Follow-Up in Adolescents, but Not Adults

    ERIC Educational Resources Information Center

    French, Simone A.; Mitchell, Nathan R.; Hannan, Peter J.

    2012-01-01

    Objective: To examine associations between television viewing, sugar-sweetened beverage consumption, eating out, physical activity, and body weight change over 1 year. Design: Secondary data analysis from randomized intervention trial. Setting: Households in the community. Participants: Adults (n = 153) and adolescents (n = 72) from the same…

  9. Genetic evaluation of weaning weight and probability of lambing at 1 year of age in Targhee lambs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to investigate genetic control of 120-day weaning weight and the probability of lambing at 1 year of age in Targhee ewe lambs. Records of 5,967 ewe lambs born from 1989 to 2012 and first exposed to rams for breeding at approximately 7 months of age were analyzed. Reco...

  10. Endovascular Treatment of a Bleeding Secondary Aorto-Enteric Fistula. A Case Report with 1-Year Follow-up

    SciTech Connect

    Brountzos, Elias N. Vasdekis, Spyros; Kostopanagiotou, Georgia; Danias, Nikolaos; Alexopoulou, Efthymia; Petropoulou, Konstantina; Gouliamos, Athanasios; Perros, Georgios

    2007-09-15

    We report a patient with life-threatening gastrointestinal bleeding caused by a secondary aorto-enteric fistula. Because the patient had several comorbid conditions, we successfully stopped the bleeding by endovascular placement of a bifurcated aortic stent-graft. The patient developed periaortic infection 4 months later, but he was managed with antibiotics. The patient is well 1 year after the procedure.

  11. Effects on Metabolic Health after a 1-Year-Lifestyle Intervention in Overweight and Obese Children: A Randomized Controlled Trial

    PubMed Central

    Waling, Maria; Bäcklund, Catharina; Lind, Torbjörn; Larsson, Christel

    2012-01-01

    Objective. To evaluate the effect of a family-based intervention on anthropometric and metabolic markers in overweight and obese children. Methods. Overweight or obese 8–12 years olds (n = 93) were randomized into intervention or control groups. The intervention group participated in a program aiming for lifestyle changes regarding food habits and physical activity. Anthropometric measures and venous blood samples were collected from all children at baseline and after 1 year. Results. BMI z-scores decreased in both groups, 0.22 (P = 0.002) and 0.23 (P = 0.003) in intervention and control group, respectively, during the 1-year study, but there was no difference in BMI between the groups at 1-year measurement (P = 0.338). After 1 year, there was a significant difference in waist circumference, waist/hip ratio, and apolipoprotein B/A1 ratio between intervention and control group. Conclusions. The intervention had limited effects on anthropometrics and metabolic markers, which emphasizes the need of preventing childhood overweight and obesity. PMID:21941639

  12. A randomized double-blind clinical trial of posterior composite restorations with or without bevel: 1-year follow-up

    PubMed Central

    COELHO-DE-SOUZA, Fábio Herrmann; CAMARGO, Junara Cristina; BESKOW, Tiago; BALESTRIN, Matheus Dalmolin; KLEIN-JÚNIOR, Celso Afonso; DEMARCO, Flávio Fernando

    2012-01-01

    Objective This randomized double-blind clinical trial compared the performance of posterior composite restorations with or without bevel, after 1-year follow-up. Material and Methods Thirteen volunteers requiring at least two posterior composite restorations were selected. Twenty-nine cavities were performed, comprising 14 without bevel (butt joint) and 15 with bevel preparation of the enamel cavosurface angle. All cavities were restored with simplified adhesive system (Adper Single Bond) and composite resin (Filtek P60). A halogen light curing unit was used through the study. Restorations were polished immediately. Analysis was carried out at baseline, after 6 months and after 1 year by a calibrated evaluator (Kappa), according to the FDI criteria. Data were statistically analyzed by Mann-Whitney test (p<0.05). Results Beveled and non-beveled cavities performed similarly after 1 year follow-up, regarding to fractures and retention, marginal adaptation, postoperative hypersensitivity, recurrence of caries, surface luster and anatomic form. However, for surface and marginal staining, beveled cavities showed significantly better performance (p<0.05) than butt joint restorations. Conclusions It was concluded that the restorations were acceptable after 1 year, but restorations placed in cavities with marginal beveling showed less marginal staining than those placed in non-beveled cavities. PMID:22666833

  13. Improving Academic Performance of School-Age Children by Physical Activity in the Classroom: 1-Year Program Evaluation

    ERIC Educational Resources Information Center

    Mullender-Wijnsma, Marijke J.; Hartman, Esther; de Greeff, Johannes W.; Bosker, Roel J.; Doolaard, Simone; Visscher, Chris

    2015-01-01

    Background: An intervention was designed that combined physical activity with learning activities. It was based upon evidence for positive effects of moderate to vigorous physical activity (MVPA) on academic achievement. The aim of this study was to describe the program implementation and effects on academic achievement after 1?year. Methods:…

  14. Survival After Relapse of Medulloblastoma.

    PubMed

    Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

    2016-05-01

    Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations. PMID:26907655

  15. Validation of survivability validation protocols

    SciTech Connect

    Stringer, T.A. )

    1993-05-01

    Issues associated with the validation of survivability protocols are discussed. Both empirical and analytical approaches to protocol validation are included. The use of hybrid simulations (hardware-in-the-loop, scene generators, software generators, man-in-the-loop, etc.) for the validation of survivability protocols is discussed.

  16. The effect of solar-geomagnetic activity during hospital admission on coronary events within 1 year in patients with acute coronary syndromes

    NASA Astrophysics Data System (ADS)

    Vencloviene, J.; Babarskiene, R.; Milvidaite, I.; Kubilius, R.; Stasionyte, J.

    2013-12-01

    Some evidence indicates the deterioration of the cardiovascular system during space storms. It is plausible that the space weather conditions during and after hospital admission may affect the risk of coronary events in patients with acute coronary syndromes (ACS). We analyzed the data of 1400 ACS patients who were admitted to the Hospital Lithuanian University of Health Sciences, and who survived for more than 4 days. We evaluated the associations between geomagnetic storms (GS), solar proton events (SPE), and solar flares (SF) that occurred 0-3 days before and after hospital admission and the risk of cardiovascular death (CAD), non-fatal ACS, and coronary artery bypass grafting (CABG) during a period of 1 year; the evaluation was based on the multivariate logistic model, controlling for clinical data. After adjustment for clinical variables, GS occurring in conjunction with SF 1 day before admission increased the risk of CAD by over 2.5 times. GS 2 days after SPE occurred 1 day after admission increased the risk of CAD and CABG by over 2.8 times. The risk of CABG increased by over 2 times in patients admitted during the day of GS and 1 day after SPE. The risk of ACS was by over 1.63 times higher for patients admitted 1 day before or after solar flares.

  17. Improvement in insulin sensitivity following a 1-year lifestyle intervention program in viscerally obese men: contribution of abdominal adiposity.

    PubMed

    Borel, Anne-Laure; Nazare, Julie-Anne; Smith, Jessica; Alméras, Natalie; Tremblay, Angelo; Bergeron, Jean; Poirier, Paul; Després, Jean-Pierre

    2012-02-01

    The objectives of the study were to quantify the effect of a 1-year healthy eating-physical activity/exercise lifestyle modification program on insulin sensitivity in viscerally obese men classified according to their glucose tolerance status and to evaluate the respective contributions of changes in body fat distribution vs changes in cardiorespiratory fitness (CRF) to the improvements in indices of plasma glucose/insulin homeostasis. Abdominally obese, dyslipidemic men (waist circumference ≥90 cm, triglycerides ≥1.69 mmol/L, and/or high-density lipoprotein cholesterol <1.03 mmol/L) were recruited. The 1-year intervention/evaluation was completed by 104 men. Body weight, composition, and fat distribution were assessed by dual-energy x-ray absorptiometry/computed tomography. Cardiorespiratory fitness and cardiometabolic risk profile were measured. After 1 year, insulin sensitivity improved in association with decreases in both visceral (VAT) and subcutaneous adiposity (SAT) as well as with the improvement in CRF, regardless of baseline glucose tolerance. Further analyses were performed according to changes in glucose tolerance status: improvement (group I, n = 39), no change (group N, n = 50), or worsening (group W, n = 15) after 1 year. Groups I and N improved their insulin sensitivity and their CRF, whereas group W did not, while losing less VAT than groups I and N. Multiple regressions showed that reduction in VAT was associated with an improvement in homeostasis model assessment of insulin resistance, whereas reduction in SAT was rather associated with improvement of the insulin sensitivity index of Matsuda. Changes in CRF were not independently associated with changes in indices of plasma glucose/insulin homeostasis. A 1-year lifestyle intervention improved plasma glucose/insulin homeostasis in viscerally obese men, including those with normal glucose tolerance status at baseline. Changes in SAT and VAT but not in CRF appeared to mediate these improvements

  18. Prevalence and Predictive Factors of Chronic Postsurgical Pain and Global Surgical Recovery 1 Year After Outpatient Knee Arthroscopy

    PubMed Central

    Hoofwijk, Daisy M.N.; Fiddelers, Audrey A.A.; Emans, Peter J.; Joosten, Elbert A.; Gramke, Hans-Fritz; Marcus, Marco A.E.; Buhre, Wolfgang F.F.A.

    2015-01-01

    Abstract Outpatient knee arthroscopy is one of the most commonly performed surgical procedures. Previous research has demonstrated that chronic postsurgical pain (CPSP) after outpatient surgery is prevalent. Our objective was to determine the prevalence and predictive factors of CPSP and Global Surgical Recovery (GSR) 1 year after knee arthroscopy. A prospective longitudinal cohort study was performed. Patients were included during an 18-month period. Data were collected by using 3 questionnaires: at 1 week preoperatively, 4 days postoperatively, and 1 year postoperatively. A value of >3 on an 11-point numeric rating scale (NRS) was defined as moderate to severe pain. A score of ≤80% on the Global Surgical Recovery Index was defined as poor GSR. Stepwise logistic regression analysis was performed to determine which variables were predictors for CPSP and poor GSR. The prevalence of moderate to severe preoperative pain in patients undergoing knee arthroscopy (n = 104) was 71.2%, of acute postsurgical pain 37.5%, and of CPSP 32.7%. Risk factors for CPSP were the presence of preoperative pain and preoperative analgesic use, with odds ratios of 6.31 (1.25–31.74) and 4.36 (1.58–12.07), respectively. The prevalence of poor GSR 1 year after outpatient knee arthrosocpy was 50.0%. Poor GSR 4 days after the surgery was a risk factor with an odds ratio of 8.38 (0.92–76.58) and quality of life 4 days after surgery was a protective factor with and odds ratio of 0.10 (0.02–0.64). Both CPSP and poor GSR are common 1 year after knee arthroscopy. Patients at risk for CPSP can be identified during the preoperative phase. Prediction of poor GSR 1 year after surgery is mainly related to early postoperative recovery. PMID:26559300

  19. CA-125–indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery

    PubMed Central

    2013-01-01

    Background There is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR) to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS). Methods We identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration. Results The CA-125 level of 1.68 × nadir was defined as the indicator of recurrent disease (p < 0.001). The specificity and sensitivity of this criterion were 82.9% and 85.6%, respectively, and the median lead-time of the CA-125 biochemical progression prior to clinically-defined relapse was 31 days (ranging from 1 to 391 days). The median number of the negative imaging studies for the clinical relapse findings in patients with a CA-125 level of < 1.68 × nadir was 3 (ranging from 0 to 24 times). The increase of CA-125 level at relapse was an independent predictor of overall and progression free survival in patients who had shown CCR to primary therapy (p = 0.04 and 0.02 respectively). The overall and progression free survival durations in patients with a CA-125 level ≤ 1.68 × nadir at relapse (69.4 and 13.8 months) were longer than those with a CA-125 level > 1.68 × nadir at relapse (55.7 and 10.4 months; p = 0.04 and 0.01, respectively). The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of

  20. Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31-32 deletion as a prognostic factor in myeloma

    PubMed Central

    Chng, WJ; Gertz, MA; Chung, T-H; Van Wier, S; Keats, JJ; Baker, A; Bergsagel, PL; Carpten, J; Fonseca, R

    2010-01-01

    In this study, we correlated array-comparative genomic hybridization-defined abnormalities with survival in two different cohorts of patients treated with therapy based on high-dose melphalan with autologous stem-cell transplantation (64 from the Mayo Clinic and 67 from the University of Arkansas Medical School) and identified that several regions of genomic gains and losses were significantly associated with poorer survival. Three noncontiguous survival relevant regions covering 1p31-33 and two noncontiguous regions covering 20p12.3-12.1 were common between the two datasets. The prognostic relevance of these hotspots was validated in an independent cohort using fluorescent in situ hybridization, which showed that 1p31-32 loss is significantly associated with shorter survival (24.5 months versus 40 months, log-rank P-value=0.01), whereas 20p12 loss has a trend toward shorter survival (26.3 months versus 40 months, log-rank P-value=0.06). On multivariate analysis, 1p31-32 loss is an independent prognostic factor. On further analysis, the prognostic impact of 1p31-32 loss is due to shortening of post-relapse survival as there is no impact on complete response rates and progression-free survival. PMID:20220778

  1. Satellite Survivability Module

    NASA Astrophysics Data System (ADS)

    Buehler, P.; Smith, J.

    The Satellite Survivability Module (SSM) is an end-to-end, physics-based, performance prediction model for directed energy engagement of orbiting spacecraft. SSM was created as an add-on module for the Satellite Tool Kit (STK). Two engagement types are currently supported: laser engagement of the focal plane array of an imaging spacecraft; and Radio Frequency (RF) engagement of spacecraft components. This paper will focus on the laser engagement scenario, the process by which it is defined, and how we use this tool to support a future laser threat detection system experiment. For a laser engagement, the user creates a spacecraft, defines its optical system, adds any protection techniques used by the optical system, introduces a laser threat, and then defines the atmosphere through which the laser will pass. SSM models the laser engagement and its impact on the spacecraft's optical system using four impact levels: degradation, saturation, damage, and destruction. Protection techniques, if employed, will mitigate engagement effects. SSM currently supports two laser protection techniques. SSM allows the user to create and implement a variety of "what if" scenarios. Satellites can be placed in a variety of orbits. Threats can be placed anywhere on the Earth or, for version 2.0, on other satellites. Satellites and threats can be mixed and matched to examine possibilities. Protection techniques for a particular spacecraft can be turned on or off individually; and can be arranged in any order to simulate more complicated protection schemes. Results can be displayed as 2-D or 3-D visualizations, or as textual reports. A new report feature available in version 2.0 will allow laser effects data to be displayed dynamically during scenario execution. In order to test SSM capabilities, the Ball team used SSM to model several engagement scenarios for our future laser threat detection system experiment. Actual test sites, along with actual laser, optics, and detector

  2. Marketing child survival.

    PubMed

    Grant, J P

    1984-01-01

    Growth monitoring charts, packets of oral rehydration salts (ORS), and vaccines, are inexpensive, life-saving, growth-protecting technologies which can enable parents to protect their children against the worst effects of poverty. Similarly, a matrix of current and easily understandable information about pregnancy, breast feeding, weaning, feeding during and immediately after illness, child spacing, and preparing and using home-made oral rehydration solutions, also could empower parents to protect the lives and the health of their children. The question arises as to how can these technologies and this information be put at the disposal of millions of families in the low-income world. The initial task of the Child Survival and Development Revolution is the communication of what is now possible, yet little is known about how to communicate information whose principal value is to the poor. There are 2 large-scale precedents: the Green Revolution, which in many instances succeeded in putting into the hands of thousands of small and large farmers the techniques and the knowledge which enabled them to double and treble the yields from their lands; and the campaign to put the knowledge and the means of family planning at the disposal of many millions of people. There are 2 lessons to be learned from these precedents: they have shown that the way to promote a people's technology and to put information at the disposal of the majority is by mobilizing all possible resources and working through all possible channels both to create the demand and to meet it; and neither the Green Revolution nor the family planning movement rally took off until they were viewed as political and economic priorities and given the full support of the nation's political leadership. Nowhere are these 2 lessons more clearly illustrated than in present-day Indonesia. Because the campaign for family planning was given high personal and political priority by the President, and because 85% of all family

  3. Intraocular lymphoma in Korea: the Consortium for Improving Survival of Lymphoma (CISL) study

    PubMed Central

    Lee, Seul; Kim, Moon Jin; Kim, Jin Seok; Kim, Seok Jin; Kwon, Yoon Hyung; Chung, In Young; Kang, Jung Hun; Yang, Deok-Hwan; Kang, Hye Jin; Yoon, Dok Hyun; Kim, Won Seog; Kim, Hyo-Jin

    2015-01-01

    Background Intraocular lymphoma (IOL) is a rare malignant lymphoma that most closely resembles a diffuse large B-cell lymphoma, and it is a subtype of primary central nervous system lymphoma (PCNSL). IOL is located inside the eye in the retina, uvea, and/or optic nerve. We retrospectively analyzed IOL patient data to identify treatment patterns and survival rates in Korea. Methods Cytological confirmation for a diagnosis of IOL was performed for all patients. The clinical data collected from medical records included Ann Arbor stage, International Prognostic Index, performance status, date of diagnosis, treatment modality and response, date of relapse, and date of last follow-up. Results Twenty patients who were diagnosed with IOL, between December 2007 and June 2014 at multiple centers in Korea, were included in the analysis. Four patients were diagnosed with IOL alone, not involving the CNS. Two patients with isolated IOL later developed PCNSL. Nine patients developed CNS lesions before the onset of ocular lymphoma. Five patients had simultaneous onset in the eye and CNS. Twelve patients were treated by intravitreal injection of methotrexate for IOL. The median progression-free survival (PFS) for patients was 19.7 months (95% CI, 8.7-30.7 mo). The estimated 3-year overall survival (OS) for all patients was 75.1%. Conclusion Treatment for IOL patients included radiotherapy and intraocular chemotherapy. IOL patients showed favorable PFS and OS. These patients would require long-term follow-up to identify relapse and adverse effects of radiotherapy or intraocular chemotherapy. PMID:26770952

  4. Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy

    PubMed Central

    Österlund, P; Soveri, L-M; Isoniemi, H; Poussa, T; Alanko, T; Bono, P

    2011-01-01

    Background: Hypertension (HTN) is a common toxicity of anti-VEGF (vascular endothelial growth factor) antibody treatment. It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and bevacizumab. Methods: A total of 101 consecutive patients with mCRC were treated with standard chemotherapy combined with bevacizumab at dose of 2.5 mg kg−1 per week in a single centre. The median follow-up time of the patients alive was 64 months. Blood pressure was measured before each bevacizumab infusion, and HTN was graded according to common toxicity criteria for adverse events version 3.0. Results: Overall, 57 patients (56%) developed ⩾grade 1 HTN (median blood pressure 168/97 mm Hg), whereas 44 (44%) remained normotensive when treated with bevacizumab-containing chemotherapy regimen. Overall response rate was higher among patients with HTN (30 vs 20% P=0.025). Hypertension was associated with improved progression-free survival (10.5 vs 5.3 months; P=0.008) and overall survival (25.8 vs 11.7 months; P<0.001), and development of HTN within 3 months had an independent, prognostic influence in a multivariate landmark survival analysis together with other known mCRC prognostic factors (P=0.007). There was no association between HTN and development of thromboembolic complications. Conclusion: Hypertension may predict outcome of bevacizumab-containing chemotherapy in mCRC. These data require confirmation in prospective studies including pharmacodynamic and pharmacokinetic analyses. PMID:21304526

  5. Patterns of Improved Survival in Patients With Multiple Myeloma in the Twenty-First Century: A Population-Based Study

    PubMed Central

    Turesson, Ingemar; Velez, Ramon; Kristinsson, Sigurdur Y.; Landgren, Ola

    2010-01-01

    Purpose Randomized multiple myeloma (MM) studies show improved response rates and better progression-free survival for newer therapies. However, a less pronounced effect has been found for overall survival (OS). Using population-based data including detailed treatment information for individual patients, we assessed survival patterns for all patients diagnosed with MM in Malmö, Sweden from 1950 to 2005. Patients and Methods We identified 773 patients with MM (48% males). On the basis of the age limit used for treatment with high-dose melphalan with autologous stem-cell support (HDM-ASCT; ≤ 65 years old) in Sweden, we constructed Kaplan-Meier curves and used the Breslow generalized Wilcoxon test to evaluate OS patterns (diagnosed in six calendar periods) for patients 65 years old or younger and patients older than 65 years. Results Including all age groups, patients diagnosed from 1960 to 1969 had a better survival than patients diagnosed from 1950 to 1959. In subsequent 10-year calendar periods, median OS increased from 24.3 to 56.3 months (P = .036) in patients ≤ 65 years old. In contrast, OS did not improve among patients older than age 65 years (21.2 to 26.7 months, P = .7). Conclusion With the establishment of HDM-ASCT as the standard therapy for younger patients with MM, OS has improved significantly for this age group in the general MM population. With novel therapies being commonly used at disease progression, presumably it becomes increasingly difficult to confirm survival differences between defined induction, consolidation, and maintenance therapies in the future. Consequently, in the era of novel MM therapies, population-based studies will serve as a necessary complement to randomized trials. PMID:20038719

  6. High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Ang, Mei-Kim; Patel, Mihir R.; Yin, Xiao-Ying; Sundaram, Sneha; Fritchie, Karen; Zhao, Ni; Liu, Yufeng; Freemerman, Alex J.; Wilkerson, Matthew D.; Walter, Vonn; Weissler, Mark C.; Shockley, William W.; Couch, Marion E.; Zanation, Adam M.; Hackman, Trevor; Chera, Bhishamjit S.; Harris, Stephen L.; Miller, C. Ryan; Thorne, Leigh B.; Hayward, Michele C.; Funkhouser, William K.; Olshan, Andrew F.; Shores, Carol G.; Makowski, Liza; Hayes, D. Neil

    2012-01-01

    Purpose We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome. Experimental Design XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1). Results Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44–8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16INK4a-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52–4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06–0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36–15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08–0.92, respectively; P = 0.037). Conclusions In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment. PMID:21908577

  7. High ERCC1 expression is associated with platinum-resistance, but not survival in patients with epithelial ovarian cancer

    PubMed Central

    Du, Pei; Wang, Yifeng; Chen, Liquan; Gan, Yaping; Wu, Qinian

    2016-01-01

    The present study aimed to investigate the association between excision repair cross-complementation group 1 (ERCC1) expression and clinical resistance to platinum-based chemotherapy or clinical characteristics, including survival time, in patients with epithelial ovarian cancer (EOC). ERCC1 expression was determined by immunohistochemical staining in 92 tumor specimens from patients with EOC. The effect of ERCC1 expression on progression-free survival time (PFS) or overall survival time (OS), and its association with clinical resistance to platinum-based chemotherapy was investigated by Kaplan-Meier survival analysis, Cox regression analysis and the χ2 test. Of 92 patients with EOC, 89.13% (82/92) had ERCC1-positive tumors. The positive rate was significantly higher in platinum-resistant patients compared with those who were platinum-responding (P<0.05). The PFS and median OS were 12 and 30 months, respectively, in ERCC1 high expression patients, and 17 and 39 months, respectively, in ERCC1 low expression patients. However, there was no statistically significant difference in PFS (P=0.099) or OS (P=0.103) between the high and low expression groups. Furthermore, it was identified that ERCC1 was not an independent factor affecting the prognosis of patients with EOC based on Cox proportional hazards regression analysis. These results demonstrate that high ERCC1 expression is associated with resistance to platinum-based chemotherapy, but not with survival time, and ERCC1 protein expression is not an independent factor or the only factor affecting the prognosis of patients with EOC. PMID:27446360

  8. Frequency of abnormal findings detected by comprehensive clinical evaluation at 1 year after allogeneic hematopoietic cell transplantation.

    PubMed

    Lee, Stephanie J; Seaborn, Travis; Mao, Frances J; Massey, Susan C; Luu, Ngoc Q; Schubert, Mary A; Chien, Jason W; Carpenter, Paul A; Moravec, Carina; Martin, Paul J; Flowers, Mary E D

    2009-04-01

    Consensus guidelines recommend various screening examinations for survivors after allogeneic hematopoietic cell transplantation (HCT), but how often these examinations detect abnormal findings is unknown. We reviewed the medical records of 118 patients who received comprehensive, standardized evaluations at 1 year after allogeneic HCT at Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance. Abnormal findings were common, including moderate to severe pulmonary dysfunction (16%), fasting hyperlipidemia (56%), osteopenia (52%), osteoporosis (6%), and active chronic graft-versus-host disease (cGVHD) (64%). Recurrent malignancy (4%) and cGVHD (29%) were detected in previously unsuspected cases. Only 3% of patients had no abnormal findings. We conclude that comprehensive evaluation at 1 year after allogeneic HCT detects a high prevalence of medical problems. Longer follow-up is needed to determine whether early detection and intervention affect later morbidity and mortality. PMID:19285628

  9. Epigenetic Analysis of Neurocognitive Development at 1 year of Age in a Community-Based Pregnancy Cohort

    PubMed Central

    Murphy, Laura E.; Palmer, Frederick B.; Graff, J. Carolyn; Sutter, Thomas R.; Mozhui, Khyobeni; Hovinga, Collin A.; Thomas, Fridtjof; Park, Vicki; Tylavsky, Frances A.; Adkins, Ronald M.

    2014-01-01

    Multiple studies show that molecular genetic changes and epigenetic modifications affect the risk of cognitive disability or impairment. However, the role of epigenetic variation in cognitive development of neurotypical young children remains largely unknown. Using data from a prospective, community-based study of mother-infant pairs, we investigated the association of DNA methylation patterns in neonatal umbilical cord blood with cognitive and language development at 1 year of age. No CpG loci achieved genome-wide significance, although a small number of weakly suggestive associations with Bayley-III Receptive Communication scales were noted. While umbilical cord blood is a convenient resource for genetic analyses of birth outcomes, our results do not provide conclusive evidence that its use for DNA methylation profiling yields epigenetic markers that are directly related to postnatal neurocognitive outcomes at 1 year of age. PMID:24452678

  10. Behaviors of children exposed to intimate partner violence before and 1 year after a treatment program for their mother.

    PubMed

    McFarlane, Judith M; Groff, Janet Y; O'brien, Jennifer A; Watson, Kathy

    2005-02-01

    Children exposed to intimate partner violence against their mothers are at increased risk for emotional, behavior, physiological, cognitive, and social problems. To compare the behavioral functioning of children exposed to intimate partner violence before and 1 year after their mother received treatment, 206 Black, White, and Hispanic children, age 18 months to 18 years, were administered the Child Behavior Checklist. Behavior problems of all children significantly improved 1 year following treatment of their mother. When compared with a clinically referred sample of youngsters, scores of children of abused mothers were not significantly different before their mothers received treatment but most scores were significantly different after their mothers were treated. Screening and a treatment for abused women can have a positive effect on the behavior of their children. PMID:15812730

  11. Emergency contraception with a Copper IUD or oral levonorgestrel: an observational study of 1-year pregnancy rates

    PubMed Central

    Turok, David K.; Jacobson, Janet C.; Dermish, Amna I.; Simonsen, Sara E.; Gurtcheff, Shawn; McFadden, Molly; Murphy, Patricia A.

    2014-01-01

    Objective We investigated the one-year pregnancy rates for emergency contraception (EC) users who selected the copper T380 IUD or oral levonorgestrel (LNG) for EC. Study Design This prospective study followed women for 1 year after choosing either the copper T380 IUD or oral LNG for EC. The study was powered to detect a 6% difference in pregnancy rates within the year after presenting for EC. Results Of the 542 women who presented for EC, agreed to participate in the trial, and meet inclusion criteria, 215 (40%) chose the copper IUD and 327 (60%) chose oral LNG. In the IUD group, 127 (59%) were nulligravid. IUD insertion failed in 42 women (19%). The 1-year follow-up rate was 443/542 (82%); 64% of IUD users contacted at 1 year still had their IUDs in place. The 1-year cumulative pregnancy rate in women choosing the IUD was 6.5% vs. 12.2% in those choosing oral LNG (HR= 0.53, 95% CI: 0.29–0.97, p=0.041). By type of EC method actually received, corresponding values were 5.2% for copper IUD users vs. 12.3% for oral LNG users, HR 0.42 (95% CI: 0.20–0.85, p= 0.017). A multivariable logistic regression model controlling for demographic variables demonstrates that women who chose the IUD for EC had fewer pregnancies in the following year than those who chose oral LNG (HR 0.50, 95% CI: 0.26–0.96, p=0.037). Conclusion One year after presenting for EC women choosing the copper IUD for EC were half as likely to have a pregnancy compared to those choosing oral LNG. PMID:24332433

  12. Prevalence, Course, Incidence, and 1-Year Prediction of Deliberate Self-Harm and Suicide Attempts in Early Norwegian School Adolescents

    ERIC Educational Resources Information Center

    Larsson, Bo; Sund, Anne Mari

    2008-01-01

    In this survey of early Norwegian school adolescents, the prevalence, course, and incidence of self-harm behavior with or without suicide intent were examined, in addition to predictors of self-harm for a 1-year follow-up period. Lifetime prevalence rates of self-harm without suicide intent and suicide attempts were 2.9% and 3.0%, respectively,…

  13. Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies

    PubMed Central

    Utz, Kathrin S.; Lee, De-Hyung; Lämmer, Alexandra; Waschbisch, Anne; Linker, Ralf A.; Schenk, Thomas

    2016-01-01

    Objectives: Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing–remitting MS (RRMS) treated with DMTs over 1 year. Methods: Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients (n = 41) corresponds to the stability in healthy individuals (n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod (n = 22) with patients treated with natalizumab (n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change. Results: Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability. Conclusions: Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI

  14. An associative learning deficit in 1-year-old infants of depressed mothers: role of depression duration.

    PubMed

    Kaplan, Peter S; Danko, Christina M; Diaz, Andres; Kalinka, Christina J

    2011-02-01

    The effectiveness of infant-directed speech (IDS) produced by non-depressed mothers for promoting the acquisition of voice-face associations was investigated in 1-year-old children of depressed mothers in a conditioned-attention paradigm. Prior research suggested that infants of mothers with comparatively longer-duration depressive episodes exhibit poorer learning in response to non-depressed mothers' IDS, but duration of depression was confounded with infant age. In the current study, 1-year-old infants of currently depressed mothers with relatively longer-duration depressive episodes (i.e., perinatal onset) showed significantly poorer learning than 1-year-olds of currently depressed mothers with relatively shorter duration depressive episodes (non-perinatal onset). This was true despite the fact that there were no measurable differences in the severity of depression, level of social functioning, or antidepressant medication use between the two groups. These findings add support to the hypothesis that there is an experience-based change in responsiveness to female IDS in infants of depressed mothers during the first year of life. PMID:21071090

  15. Low-dose acitretin in Papillon-Lefèvre syndrome: treatment and 1-year follow-up.

    PubMed

    Sarma, Nilendu; Ghosh, Chiranjit; Kar, Sudipta; Bazmi, Badruddin Ahmed

    2015-01-01

    The Papillon-Lefèvre syndrome (PLS) is a rare, autosomal recessive disease that manifests with palmoplantar keratoderma and destructive periodontitis resulting in early onset periodontal breakdown in deciduous and permanent dentition. Management of this condition is difficult. Here we report one 11-year-old consanguineous Muslim boy suffering from PLS. After failing to get any benefit from methotrexate, three cycles of acitretin, each for 2 months, were given 1 month apart. In each cycle, acitretin (25 mg) was given every other day. At the end of the third cycle, treatment was stopped for 4 months to observe the extent of relapse. Thereafter, acitretin (25 mg) was given twice weekly for 4 months and then the patient was followed up for 1 year. Treatment with acitretin resulted in excellent improvement of periodontitis, increase in the alveolar bone height, and periodontal attachment. Improvement remained stable at the end of 1-year follow-up. There was excellent (>75%) improvement in keratoderma at the end of active therapy. Mild worsening of palmoplantar keratoderma was noticed whenever the drug was stopped. It improved when the drug was restarted. Other areas remained stable. At the end of 1-year follow-up, good improvement (50%) in palmoplantar keratoderma was achieved. PMID:25313946

  16. Follow-up of a 1-year media campaign on delay times and ambulance use in suspected acute myocardial infarction.

    PubMed

    Herlitz, J; Blohm, M; Hartford, M; Karlson, B W; Luepker, R; Holmberg, S; Risenfors, M; Wennerblom, B

    1992-02-01

    In order to reduce the delay times from onset of symptoms to arrival in hospital, and increase the use of ambulance in patients with suspected acute myocardial infarction (AMI), a media campaign was initiated in an urban area. An initial 3-week intense campaign was followed by a maintenance phase of 1 year. Delay times and ambulance use during the campaign were compared with the previous 21 months. Among patients admitted to a coronary care unit (CCU) due to suspected AMI, the median delay time was reduced from 3 h to 2 h 40 min and the mean delay time was reduced from 11 h 33 min to 7 h 42 min (P less than 0.001). Among patients with confirmed AMI the median delay time was reduced from 3 h to 2 h 20 min and the mean delay time from 10 h to 6 h 27 min (P less than 0.001). We conclude that a 1-year media campaign can reduce delay times in suspected AMI, and that this effect appears to continue at 1 year, but ambulance use seems to be more difficult to influence. PMID:1555612

  17. Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

    PubMed

    Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

    2016-06-01

    Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost

  18. The role of maternal behavior and offspring development in the survival of mountain goat kids.

    PubMed

    Théoret-Gosselin, Rachel; Hamel, Sandra; Côté, Steeve D

    2015-05-01

    Studies on juvenile survival have mainly focused on the effects of environmental conditions and maternal traits. However, growing evidence indicates that the ability of parents to care for their young and the offspring developmental behaviors could be key determinants of their survival. We examined the relative influence of (1) environmental conditions, (2) offspring traits, (3) maternal traits, (4) maternal care behaviors, and (5) offspring developmental behaviors on kid survival to weaning and to 1 year old in mountain goats (Oreamnos americanus). Offspring development and maternal care directly affected offspring survival, and this more importantly than did environmental conditions and maternal traits. Frequency of play strongly increased survival before weaning. Greater maternal care increased offspring survival during winter, directly and indirectly through kid mass. Kid mass was also a major determinant of both summer and winter survival. Environmental conditions mainly influenced summer survival while maternal characteristics indirectly affected winter survival through an effect on kid mass. Behavioral adaptations of maternal care and offspring development to local selective pressures can lead to local adaptations and have greater implications in population dynamic studies than previously believed. PMID:25556294

  19. Population-based survival estimates for childhood cancer in Australia during the period 1997–2006

    PubMed Central

    Baade, P D; Youlden, D R; Valery, P C; Hassall, T; Ward, L; Green, A C; Aitken, J F

    2010-01-01

    Background: This study provides the latest available relative survival data for Australian childhood cancer patients. Methods: Data from the population-based Australian Paediatric Cancer Registry were used to describe relative survival outcomes using the period method for 11 903 children diagnosed with cancer between 1983 and 2006 and prevalent at any time between 1997 and 2006. Results: The overall relative survival was 90.4% after 1 year, 79.5% after 5 years and 74.7% after 20 years. Where information onstage at diagnosis was available (lymphomas, neuroblastoma, renal tumours and rhabdomyosarcomas), survival was significantly poorer for more-advanced stage. Survival was lower among infants compared with other children for those diagnosed with leukaemia, tumours of the central nervous system and renal tumours but higher for neuroblastoma. Recent improvements in overall childhood cancer survival over time are mainly because of improvements among leukaemia patients. Conclusion: The high and improving survival prognosis for children diagnosed with cancer in Australia is consistent with various international estimates. However, a 5-year survival estimate of 79% still means that many children who are diagnosed with cancer will die within 5 years, whereas others have long-term health morbidities and complications associated with their treatments. It is hoped that continued developments in treatment protocols will result in further improvements in survival. PMID:21063404

  20. Surviving Small-Town Practice

    PubMed Central

    Johnson, Merv

    1987-01-01

    To cope and to survive family medicine in a small town has been, and continues to be, a problem. This article presents one physician's means and methods of staying in a difficult, but extremely exciting, profession. PMID:21263791

  1. Secretarial Administration: Secretarial Survival Skills.

    ERIC Educational Resources Information Center

    Banks, Jane M.

    1978-01-01

    Secretarial survival skills of communication, organization, and decision making should be incorporated into the secretarial training program, according to the author. She discusses these skills in relation to career mobility. (MF)

  2. SURVIVAL OF BACTERIA DURING AEROSOLIZATION

    EPA Science Inventory

    One form of commercial application of microorganisms, including genetically engineered microorganisms is as an aerosol. To study the effect of aerosol-induced stress on bacterial survival, nonrecombinant spontaneous antibiotic-resistant mutants of four organisms, Enterobacter clo...

  3. Survivability of Deterministic Dynamical Systems

    PubMed Central

    Hellmann, Frank; Schultz, Paul; Grabow, Carsten; Heitzig, Jobst; Kurths, Jürgen

    2016-01-01

    The notion of a part of phase space containing desired (or allowed) states of a dynamical system is important in a wide range of complex systems research. It has been called the safe operating space, the viability kernel or the sunny region. In this paper we define the notion of survivability: Given a random initial condition, what is the likelihood that the transient behaviour of a deterministic system does not leave a region of desirable states. We demonstrate the utility of this novel stability measure by considering models from climate science, neuronal networks and power grids. We also show that a semi-analytic lower bound for the survivability of linear systems allows a numerically very efficient survivability analysis in realistic models of power grids. Our numerical and semi-analytic work underlines that the type of stability measured by survivability is not captured by common asymptotic stability measures. PMID:27405955

  4. Survivability of Deterministic Dynamical Systems

    NASA Astrophysics Data System (ADS)

    Hellmann, Frank; Schultz, Paul; Grabow, Carsten; Heitzig, Jobst; Kurths, Jürgen

    2016-07-01

    The notion of a part of phase space containing desired (or allowed) states of a dynamical system is important in a wide range of complex systems research. It has been called the safe operating space, the viability kernel or the sunny region. In this paper we define the notion of survivability: Given a random initial condition, what is the likelihood that the transient behaviour of a deterministic system does not leave a region of desirable states. We demonstrate the utility of this novel stability measure by considering models from climate science, neuronal networks and power grids. We also show that a semi-analytic lower bound for the survivability of linear systems allows a numerically very efficient survivability analysis in realistic models of power grids. Our numerical and semi-analytic work underlines that the type of stability measured by survivability is not captured by common asymptotic stability measures.

  5. The Survival of the Wisest

    ERIC Educational Resources Information Center

    Salk, Jonas

    1975-01-01

    Suggests that humans differ from other living organisms in the ability to exercise learned behavior and the individual will, which may allow people to make the changes in values necessary to survive on this planet. (DW)

  6. Survivability of Deterministic Dynamical Systems.

    PubMed

    Hellmann, Frank; Schultz, Paul; Grabow, Carsten; Heitzig, Jobst; Kurths, Jürgen

    2016-01-01

    The notion of a part of phase space containing desired (or allowed) states of a dynamical system is important in a wide range of complex systems research. It has been called the safe operating space, the viability kernel or the sunny region. In this paper we define the notion of survivability: Given a random initial condition, what is the likelihood that the transient behaviour of a deterministic system does not leave a region of desirable states. We demonstrate the utility of this novel stability measure by considering models from climate science, neuronal networks and power grids. We also show that a semi-analytic lower bound for the survivability of linear systems allows a numerically very efficient survivability analysis in realistic models of power grids. Our numerical and semi-analytic work underlines that the type of stability measured by survivability is not captured by common asymptotic stability measures. PMID:27405955

  7. Prognostic Factors and Survival in Pediatric and Adolescent Liposarcoma

    PubMed Central

    Stanelle, Eric J.; Christison-Lagay, Emily R.; Sidebotham, Emma L.; Singer, Samuel; Antonescu, Cristina R.; Meyers, Paul A.; La Quaglia, Michael P.

    2012-01-01

    Purpose. Liposarcoma is extremely rare in the pediatric population. To identify prognostic factors and determine treatment outcomes, we reviewed our institutional experience with pediatric liposarcoma. Methods. We retrospectively reviewed all pediatric patients (age <22 years) with confirmed liposarcoma treated at Memorial Sloan-Kettering Cancer Center. Histologic subtype, tumor location, margin status, recurrence, and adjuvant therapy were analyzed and correlated with overall survival. Results. Thirty-four patients (56% male) with a median age of 18.1 years were identified. Twenty-two (65%) had peripheral tumors and 12 (35%) had centrally located tumors. Histologically, 29 (85%) tumors were low grade, and 5 (15%) were high grade pleomorphic. Eleven (32%) had recurrent disease, 9 patients with central tumors and 2 patients with peripheral lesions. Eight deaths occurred, all in patients with central disease. Five-year overall survival was 78%, with a median follow-up time of 5.4 years (range, 0.3–30.3 years). Tumor grade (P = .003), histologic subtype (P = .01), and primary location (P < .001) all correlated with survival, as did stage (P < .001) and margin status (P = .001). Conclusions. Central location of the primary tumor, high tumor grade, and positive surgical margins are strongly correlated with poor survival in pediatric patients with liposarcoma. PMID:22991488

  8. Customer service skills for survival.

    PubMed

    McAtee, L F

    1999-11-01

    As APICS practitioners, we all must share a common goal. How can we contribute to our company's success? Success can be measured in positive terms of market share, growth, profitability, return on investment, or some combination thereof. Each company must establish its own definition of success. For the purposes of this article, success will be equated to one word that we can all readily identify with: survival. What skills do we need to survive in the marketplace of the next millennium? PMID:10623133

  9. Diabetes, Metformin Use, and Colorectal Cancer Survival in Postmenopausal Women

    PubMed Central

    Cossor, Furha Iram; Adams-Campbell, Lucile L.; Chlebowski, Rowan T.; Gunter, Marc J; Johnson, Karen; Martell, Robert E.; McTiernan, Anne; Simon, Michael S.; Rohan, Thomas; Wallace, Robert B.; Paulus, Jessica K.

    2013-01-01

    Background Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin’s influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study. Methods 2,066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n=84); women with diabetes with no metformin use (n=128); and women without diabetes (n=1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40 –1.38, p=0.67) and to women without diabetes (HR 1.00; 95% CI 0.61 – 1.66, p=0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38 – 1.55, p=0.47) and for overall survival was 0.86 (95% CI 0.49 – 1.52; p=0.60). Conclusions In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted. PMID:23773299

  10. Survival analysis of transarterial radioembolization with yttrium-90 for hepatocellular carcinoma patients with HBV infection

    PubMed Central

    She, Wong Hoi; Yau, Thomas C. C.; Chan, Albert C. Y.; Chok, Kenneth S. H.; Chu, Ferdinand S. K.; Liu, Rico K. Y.; Poon, Ronnie T. P.; Chan, See Ching; Fan, Sheung Tat; Lo, Chung Mau

    2014-01-01

    Introduction For patients with resectable hepatocellular carcinoma (HCC), hepatectomy remains one of the best treatment options to provide long-term survival. However, more than 50% of the patients have unresectable disease upon diagnosis even though there are no distant metastases. Transarterial chemoembolization (TACE) is a well-established treatment option that offers a palliative survival benefit for this group of patients. A better treatment for unresectable HCC has been sought after. There is some evidence that transarterial radioembolization (TARE) with the agent yttrium-90 produces encouraging outcomes, especially in patients with portal vein tumor thrombus. This study aims to analyze the outcomes of TARE at our center. Methods From August 2009 to April 2013, 16 patients underwent TARE at our center. Sixteen patients with similar tumor characteristics were selected to undergo TACE alone for comparison. A retrospective analysis of the prospectively collected data of the patients was conducted. Only patients with newly diagnosed primary tumors were included in this study. Results The median survival for patients having TARE was 19.9 versus 14.0 months in the TACE group (P=0.615). There was no difference in terms of tumor response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) (P=0.632). The 1-, 2- and 3-year survival rates in the TARE group were 80.0%, 30.5% and 20.3% respectively. The 1-year survival in the TACE group was 58.3% (P=0.615). For patients who had major vascular invasion (eight in each group), the 1- and 2-year survival rates in the TARE group were 62.5% and 15.6% respectively, while the 1-year survival in the TACE group was 35.0% (P=0.664). Conclusions The two groups showed similar results in terms of tumor response and overall survival benefit. TARE might provide a survival benefit for patients with major vessel invasion. PMID:25202695

  11. Probabilistic Survivability Versus Time Modeling

    NASA Technical Reports Server (NTRS)

    Joyner, James J., Sr.

    2015-01-01

    This technical paper documents Kennedy Space Centers Independent Assessment team work completed on three assessments for the Ground Systems Development and Operations (GSDO) Program to assist the Chief Safety and Mission Assurance Officer (CSO) and GSDO management during key programmatic reviews. The assessments provided the GSDO Program with an analysis of how egress time affects the likelihood of astronaut and worker survival during an emergency. For each assessment, the team developed probability distributions for hazard scenarios to address statistical uncertainty, resulting in survivability plots over time. The first assessment developed a mathematical model of probabilistic survivability versus time to reach a safe location using an ideal Emergency Egress System at Launch Complex 39B (LC-39B); the second used the first model to evaluate and compare various egress systems under consideration at LC-39B. The third used a modified LC-39B model to determine if a specific hazard decreased survivability more rapidly than other events during flight hardware processing in Kennedys Vehicle Assembly Building (VAB).Based on the composite survivability versus time graphs from the first two assessments, there was a soft knee in the Figure of Merit graphs at eight minutes (ten minutes after egress ordered). Thus, the graphs illustrated to the decision makers that the final emergency egress design selected should have the capability of transporting the flight crew from the top of LC 39B to a safe location in eight minutes or less. Results for the third assessment were dominated by hazards that were classified as instantaneous in nature (e.g. stacking mishaps) and therefore had no effect on survivability vs time to egress the VAB. VAB emergency scenarios that degraded over time (e.g. fire) produced survivability vs time graphs that were line with aerospace industry norms.

  12. Regional Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Potential Role for Dynamic Magnetic Resonance Imaging as an Imaging Biomarker and a Survival Update from Two Prospective Clinical Trials

    PubMed Central

    Konstantinidis, Ioannis T.; Gultekin, David H.; Gönen, Mithat; Schwartz, Lawrence H.; Fong, Yuman; Allen, Peter J.; D'Angelica, Michael I.; DeMatteo, Ronald P.; Klimstra, David S.; Kemeny, Nancy E.; Jarnagin, William R.

    2015-01-01

    Background For patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC. Methods Prospectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome. Results Forty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008). Conclusions HAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome. PMID:24664624

  13. TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes.

    PubMed

    McGraw, Kathy L; Cluzeau, Thomas; Sallman, David A; Basiorka, Ashley A; Irvine, Brittany A; Zhang, Ling; Epling-Burnette, P K; Rollison, Dana E; Mallo, Mar; Sokol, Lubomir; Solé, Francesc; Maciejewski, Jaroslaw; List, Alan F

    2015-10-27

    P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to -2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome. PMID:26416416

  14. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission.

    PubMed

    Cowan, Andrew J; Stevenson, Philip A; Cassaday, Ryan D; Graf, Solomon A; Fromm, Jonathan R; Wu, David; Holmberg, Leona A; Till, Brian G; Chauncey, Thomas R; Smith, Stephen D; Philip, Mary; Orozco, Johnnie J; Shustov, Andrei R; Green, Damian J; Libby, Edward N; Bensinger, William I; Shadman, Mazyar; Maloney, David G; Press, Oliver W; Gopal, Ajay K

    2016-02-01

    Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR. PMID:26348890

  15. Tumor-Associated Macrophages Associate with Cerebrospinal Fluid Interleukin-10 and Survival in Primary Central Nervous System Lymphoma (PCNSL).

    PubMed

    Sasayama, Takashi; Tanaka, Kazuhiro; Mizowaki, Takashi; Nagashima, Hiroaki; Nakamizo, Satoshi; Tanaka, Hirotomo; Nishihara, Masamitsu; Mizukawa, Katsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

    2016-07-01

    Increased tumor-associated macrophages (TAMs) have been reported to be associated with poor prognosis in various tumors; however, the importance of TAMs in primary central nervous system lymphoma (PCNSL) has not been clarified. In 47 patients with PCNSL who were treated with high-dose methotrexate (MTX) and radiotherapy, the relationships between the infiltration levels of TAMs and the clinicopathological parameters were analyzed. Univariate analysis of the Cox proportional hazards model using continuous scales revealed that increased CD68 positive (+) TAMs was significantly associated with inferior progression-free survival (PFS) (P = 0.04), and trends were observed for the increased CD163(+)  TAMs and having shorter PFS (P = 0.05). However, increased TAMs were not associated with overall survival. Because TAMs are known to produce various cytokines, we examined the relationships between cerebrospinal fluid (CSF) cytokines and TAMs. CSF interleukin-6 (IL-6) and soluble IL-2 receptor were not correlated with the infiltration rate of TAMs; however, CSF IL-10 level was correlated with infiltration levels of CD68 and CD163(+)  TAMs. We also confirmed the expression of IL-10 in CD68(+)  and CD163(+)  TAMs by double immunostaining analysis. Our results indicate that a high level of IL-10 in CSF may be positively associated with the infiltration level of TAMs in PCNSLs. PMID:26314692

  16. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer

    PubMed Central

    Cheema, P.K.; Burkes, R.L.

    2013-01-01

    An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4–ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc. PMID:23559882

  17. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial

    PubMed Central

    Jolly, Sanjit S; Cairns, John A; Yusuf, Salim; Rokoss, Michael J; Gao, Peggy; Meeks, Brandi; Kedev, Sasko; Stankovic, Goran; Moreno, Raul; Gershlick, Anthony; Chowdhary, Saqib; Lavi, Shahar; Niemela, Kari; Bernat, Ivo; Cantor, Warren J; Cheema, Asim N; Steg, Philippe Gabriel; Welsh, Robert C; Sheth, Tej; Bertrand, Olivier F; Avezum, Alvaro; Bhindi, Ravinay; Natarajan, Madhu K; Horak, David; Leung, Raymond C M; Kassam, Saleem; Rao, Sunil V; El-Omar, Magdi; Mehta, Shamir R; Velianou, James L; Pancholy, Samir; Džavík, Vladimír

    2016-01-01

    Summary Background Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. Methods The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044. Findings Between Aug 5, 2010, and July 25, 2014, 10 732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not

  18. Risk of Recurrent Helicobacter pylori Infection 1 Year After Initial Eradication Therapy in 7 Latin American Communities

    PubMed Central

    Morgan, Douglas R.; Torres, Javier; Sexton, Rachael; Herrero, Rolando; Salazar-Martínez, Eduardo; Robert Greenberg, E.; Bravo, Luis Eduardo; Dominguez, Ricardo L.; Ferreccio, Catterina; Lazcano-Ponce, Eduardo C.; Meza-Montenegro, Maria Mercedes; Peña, Edgar M.; Peña, Rodolfo; Correa, Pelayo; Martínez, María Elena; Chey, William D.; Valdivieso, Manuel; Anderson, Garnet L.; Goodman, Gary E.; Crowley, John J.; Baker, Laurence H.

    2013-01-01

    Importance The long-term effectiveness of Helicobacter pylori eradication programs for preventing gastric cancer will depend on recurrence risk and individual and community factors. Objective To estimate risk of H pylori recurrence and assess factors associated with successful eradication 1 year after treatment. Design, Setting, and Participants Cohort analysis of 1463 randomized trial participants aged 21 to 65 years from 7 Latin American communities, who were treated for H pylori and observed between September 2009 and July 2011. Interventions Randomization to 1 of 3 treatment groups: 14-day lansoprazole, amoxicillin, and clarithromycin (triple therapy); 5-day lansoprazole and amoxicillin followed by 5-day lansoprazole, clarithromycin, and metronidazole (sequential); or 5-day lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant). Participants with a positive (13) C-urea breath test (UBT) 6 to 8 weeks posttreatment were offered voluntary re-treatment with 14-day bismuth-based quadruple therapy. Measurements Recurrent infection after a negative posttreatment UBT and factors associated with successful eradication at 1-year follow-up. Results Among participants with UBT-negative results who had a 1-year follow-up UBT (n=1091), 125 tested UBT positive, a recurrence risk of 11.5% (95% CI, 9.6%–13.5%). Recurrence was significantly associated with study site (P=.03), nonadherence to initial therapy (adjusted odds ratio [AOR], 2.94; 95% CI, 1.31–6.13; P=.01), and children in the household (AOR, 1.17; 95% CI, 1.01–1.35 per child; P=.03). Of the 281 with positive posttreatment UBT results, 138 completed re-treatment, of whom 93 tested UBT negative at 1 year. Among the 1340 who had a 1-year UBT, 80.4% (95% CI, 76.4%–83.9%), 79.8% (95% CI, 75.8%–83.5%), and 77.8% (95% CI, 73.6%–81.6%) had UBT-negative results in the triple, sequential, and concomitant groups, respectively (P=.61), with 79.3% overall effectiveness (95% CI, 77.1%–81.5%). In a

  19. A comparison of 1-year substance abuse treatment outcomes in community syringe exchange participants versus other referrals.

    PubMed

    Neufeld, Karin; King, Van; Peirce, Jessica; Kolodner, Ken; Brooner, Robert; Kidorf, Michael

    2008-09-01

    This longitudinal cohort study of 324 consecutive admissions to methadone maintenance treatment between 08/1994 and 09/1997 compared 1-year outcomes of opioid-dependent patients referred from a syringe exchange program (SEP; n=81) versus other sources (n=243). All participants received stepped-based counseling. The Addiction Severity Index was completed upon admission. Treatment outcomes were assessed using weekly urine testing and days in treatment. GEE regression models were used to evaluate the association between baseline variables and treatment outcomes. SEP referrals were older, included more males and African Americans, reported greater unemployment and heavier heroin, cocaine, and injection drug use at admission. During treatment, SEP referrals used more opioids (OR 2.57; 95% CI 1.86-3.56) and cocaine (OR 2.77; 95% CI 1.93-3.95), and were less likely to complete 1 year (35%) compared to other referrals (56%; hazard ratio 1.88; 95% CI 1.35-2.62). Nevertheless, referral source was not significantly associated with outcome when adjusted for baseline characteristics. Greater baseline frequency of substance and injection drug use, and younger age were positively associated with ongoing opioid and cocaine use. African American race and baseline unemployment were also associated with ongoing cocaine use. Younger age and greater baseline cocaine use were associated with poorer retention at 1 year. The poorer treatment response of SEP referrals is likely due to higher baseline problem severity. Specialized interventions may be required to reduce drug use and improve retention in this population. PMID:18486360

  20. Emergency re-admissions to hospital due to adverse drug reactions within 1 year of the index admission

    PubMed Central

    Davies, Emma C; Green, Christopher F; Mottram, David R; Rowe, Philip H; Pirmohamed, Munir

    2010-01-01

    AIM The proportion of re-admissions to hospital caused by ADRs is poorly documented in the UK. The aim of this study was to evaluate the impact of ADRs on re-admission to hospital after a period as an inpatient. METHODS One thousand patients consecutively admitted to 12 wards were included. All subsequent admissions for this cohort within 1 year of discharge from the index admission were retrospectively reviewed. RESULTS Of the 1000 patients included, 403 (40.3%, 95% CI 39.1, 45.4%) were re-admitted within 1 year. Complete data were available for 290 (70.2%) re-admitted patients, with an ADR contributing to admission in 60 (20.8%, 95% CI 16.4, 25.6%) patients. Presence of an ADR in the index admission did not predict for an ADR-related re-admission (10.5% vs. 7.2%, P = 0.25), or re-admission overall (47.2% vs. 41.2%, P = 0.15). The implicated drug was commenced in the index admission in 33/148 (22.3%) instances, with 37/148 (25%) commenced elsewhere since the index admission. Increasing age and an index admission in a medical ward were associated with a higher incidence of re-admission ADR. The most frequent causative drugs were anti-platelets and loop diuretics, with bleeding and renal impairment the most frequent ADRs. Over half (52/91, 57.1%) of the ADRs were judged to be definitely or possibly avoidable. CONCLUSIONS One fifth of patients re-admitted to hospital within 1 year of discharge from their index admission are re-admitted due to an ADR. Our data highlight drug and patient groups where interventions are needed to reduce the incidence of ADRs leading to re-admission. PMID:21039769

  1. BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year.

    PubMed

    Martinez-Cengotitabengoa, M; MacDowell, K S; Alberich, S; Diaz, F J; Garcia-Bueno, B; Rodriguez-Jimenez, R; Bioque, M; Berrocoso, E; Parellada, M; Lobo, A; Saiz, P A; Matute, C; Bernardo, M; Gonzalez-Pinto, A; Leza, J C

    2016-01-01

    Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs. PMID:26130821

  2. BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year

    PubMed Central

    Martinez-Cengotitabengoa, M.; MacDowell, K.S.; Alberich, S.; Diaz, F.J.; Garcia-Bueno, B.; Rodriguez-Jimenez, R.; Bioque, M.; Berrocoso, E.; Parellada, M.; Lobo, A.; Saiz, P.A.; Matute, C.; Bernardo, M.; Gonzalez-Pinto, A.; Leza, J.C.

    2016-01-01

    Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs. PMID:26130821

  3. A prospective randomized study of 1- and 2-stage sinus inlay bone grafts: 1-year follow-up.

    PubMed

    Wannfors, K; Johansson, B; Hallman, M; Strandkvist, T

    2000-01-01

    The purpose of the present study was to compare the success of and surgical differences between 1- and 2-stage sinus inlay bone grafts and implants after 1 year in function. The individual risk for implant failure in grafted areas among 1-stage patients was about twice the risk in 2-stage patients (odds ratio 2.3, CI 0.6; 8.5). The risk for implant failure in non-grafted areas was significantly lower (P < .05) than in grafted areas, regardless of the technique used. Forty edentulous patients, selected according to strict inclusion criteria from consecutive referrals, were allocated to one or other of the 2 sinus-inlay procedures. Twenty patients received bone blocks fixed by implants to the residual alveolar crest in a 1-stage procedure (group 1). In another 20 patients, particulated bone was condensed against the antral floor and left to heal for 6 months before implants were placed (group 2). An almost equal number of implants was placed in the patients of each group, 76 in the 1-stage procedure and 74 in the 2-stage procedure. Additionally, 72 and 66 implants were placed in the anterior non-grafted regions of group 1 and group 2 patients, respectively. After 1 year in function, a total of 20 implants failed in 1-stage patients, versus 11 in 2-stage patients. Sixteen and 8 implants, respectively, of these were placed in grafted bone. All but one 1-stage patient received the planned fixed prosthetic restorations, but 1 restoration was redesigned after the first year in function because of a functionally unacceptable prosthetic design. At the 1-year follow-up, one 2-stage patient lost her prosthesis as the result of multiple implant failures. Bruxism and postoperative infections were the only parameters that could be related to implant failure, however, depending on the statistical method used. PMID:11055129

  4. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study.

    PubMed

    Trotta, Antonella; Murray, Robin M; David, Anthony S; Kolliakou, Anna; O'Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L

    2016-03-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID:26373540

  5. Effectiveness of a 1-Year Resident Training Program in Clinical Research: A Controlled Before-and-After Study

    PubMed Central

    Hartmann, Mechthild; Wild, Beate; Nikendei, Christoph; Kroenke, Kurt; Niehoff, Dorothea; Henningsen, Peter; Zipfel, Stephan; Herzog, Wolfgang

    2007-01-01

    Background To increase the number of clinician scientists and to improve research skills, a number of clinical research training programs have been recently established. However, controlled studies assessing their effectiveness are lacking. Objective To investigate the effectiveness of a 1-year resident training program in clinical research. Design Controlled before-and-after study. The training program included a weekly class in clinical research methods, completion of a research project, and mentorship. Participants Intervention subjects were 15 residents participating in the 1-year training program in clinical research. Control subjects were 22 residents not participating in the training program. Measurements and Main Results Assessments were performed at the beginning and end of the program. Outcomes included methodological research knowledge (multiple-choice progress test), self-assessed research competence, progress on publications and grant applications, and evaluation of the program using quantitative and qualitative methods. Results Intervention subjects and controls were well matched with respect to research experience (5.1 ± 2.2 vs 5.6 ± 5.8 years; p = .69). Methodological knowledge improved significantly more in the intervention group compared to the control group (effect size = 2.5; p < .001). Similarly, self-assessed research competence increased significantly more in the intervention group (effect size = 1.1; p = .01). At the end of the program, significantly more intervention subjects compared to controls were currently writing journal articles (87% vs 36%; p = .003). The intervention subjects evaluated the training program as highly valuable for becoming independent researchers. Conclusions A 1-year training program in clinical research can substantially increase research knowledge and productivity. The program design makes it feasible to implement in other academic settings. PMID:17922168

  6. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study

    PubMed Central

    Trotta, Antonella; Murray, Robin M.; David, Anthony S.; Kolliakou, Anna; O’Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L.

    2016-01-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID:26373540

  7. Successful Endosonography-Guided Drainage of an Intra-Abdominal Abscess in a 1-Year-Old Infant.

    PubMed

    Ito, Yukiko; Isayama, Hiroyuki; Nakai, Yousuke; Umefune, Gyoutane; Sato, Tatsuya; Nakahara, Saori; Suwa, Junko; Kato, Keiichi; Nakata, Ryo

    2016-05-23

    Endoscopic ultrasound (EUS)-guided intervention has been established as a safe, effective and minimally invasive procedure for various diseases in adults, but there have been limited reports in pediatric patients. Herein, we report our experience with successful EUS-guided drainage of an intraabdominal abscess in a 1-year-old infant concomitant with disseminated intravascular coagulation. The abscess was punctured via the stomach using a standard, convex-type echoendoscope, and the patient's condition improved after naso-cystic catheter placement. Although the clinical course was complicated by delayed hemorrhage from the puncture site, the bleeding was successfully managed by endoscopic hemostasis using a standard forward-viewing endoscope. PMID:27114437

  8. Type B Aortic Dissection with Abdominal Aortic Aneurysm Rupture 1 Year after Endovascular Repair of Abdominal Aortic Aneurysm.

    PubMed

    Daniel, Guillaume; Ben Ahmed, Sabrina; Warein, Edouard; Gallon, Arnaud; Rosset, Eugenio

    2016-05-01

    We report a patient who developed a type B aortic dissection and ruptured his aneurysmal sac 1 year after endovascular abdominal aortic aneurysm repair (EVAR), despite standard follow-up. This 79-year-old man was presented to emergency room with acute abdominal pain and an acute lower limb ischemia. Computed tomography scan showed an acute type B aortic dissection feeding the aneurysmal sac of the EVAR. The aneurysm rupture occurred during imaging. Type B aortic dissection is a rare cause of aneurysmal rupture after EVAR. The first postoperative computed tomography scan should maybe include the arch and the descending thoracic aorta to rule out an iatrogenic dissection after EVAR. PMID:26902937

  9. [Aberration corrected intraocular lens for microincision cataract surgery (MICS). Intraindividual comparison with a conventional lens - 1-year follow-up].

    PubMed

    Möglich, M; Häberle, H; Pham, D T; Wirbelauer, C

    2009-10-01

    Microincision cataract surgery (MICS) is an important advancement in the field of cataract surgery. This article compares an aberration corrected hydrophilic acrylic intraocular lens (IOL) having a hydrophobic surface for MICS with a one-piece hydrophobic acrylic IOL with respect to capsule sac stability, image quality, and after-cataract formation over the course of 1 year. The operations were performed as bimanual MICS or coaxial phacoemulsification. Overall the results after implantation of the IOL by MICS can be regarded as positive in comparison to the standard operation. PMID:18836727

  10. Impact of Renal Sympathetic Denervation on Left Ventricular Structure and Function at 1-Year Follow-Up

    PubMed Central

    de Sousa Almeida, Manuel; de Araújo Gonçalves, Pedro; Branco, Patricia; Mesquita, João; Carvalho, Maria Salomé; Dores, Helder; Silva Sousa, Henrique; Gaspar, Augusta; Horta, Eduarda; Aleixo, Ana; Neuparth, Nuno; Mendes, Miguel; Andrade, Maria João

    2016-01-01

    Background Catheter-based sympathetic renal denervation (RDN) is a recent therapeutic option for patients with resistant hypertension. However, the impact of RDN in left ventricular (LV) mass and function is not completely established. Our aim was to evaluate the effects of RDN on LV structure and function (systolic and diastolic) in patients with resistant hypertension (HTN). Methods and Results From a single centre prospective registry including 65 consecutive patients with resistant HTN submitted to RDN between July-2011 and April-2015, 31 patients with baseline and 1-year follow-up echocardiogram were included in this analysis. Mean age was 65±7 years, 48% were males, 71% had type 2 diabetes. Most had hypertension lasting for more than 10 years (90%), and were being treated with a median number of 6 anti-hypertensive drugs, including 74% on spironolactone. At 1-year, there was a significant decrease both on office SBP (176±24 to 149±13mmHg, p<0.001) and DBP (90±14 to 79±11mmHg, p<0.001), and also in 24h ABPM SBP (150±20 to 132±14mmhg, p<0.001) and DBP (83±10 to 74±9mmHg, p<0.001). There was also a significant decrease in LV mass from 152±32 to 136±34g/m2 (p<0.001), an increase in LV end diastolic volume (93±18 to 111±27 mL, p = 0.004), an increase in LV ejection fraction (65±9 to 68±9%, p = 0.001) and mitral valve E deceleration time (225±49 to 247±51ms, p = 0.015) at 1-year follow up. There were no significant changes in left atrium volume index or in the distribution of patients among the different left ventricle geometric patterns and diastolic function subgroups. Conclusions In this single centre registry of patients with resistant hypertension, renal denervation was associated with significant reduction in both office and ABPM blood pressure and a significant decrease in left ventricle mass evaluated by transthoracic echocardiogram at 1 year follow-up. PMID:26934735

  11. Probable transmission of Yersinia enterocolitica from a pet dog with diarrhoea to a 1-year-old infant.

    PubMed

    Hetem, D J; Pekelharing, M; Thijsen, S F T

    2013-01-01

    We report a highly probable case of transmission of a Yersinia enterocolitica from a pet puppy dog, adopted from a Spanish asylum, to a 1-year-old girl. After several weeks of diarrhoea, a PCR detecting enteropathogenic bacteria was performed on the faeces, revealing Y enterocolitica. Following cultures yielded a Y enterocolitica biotype 4, serotype O:3 in the faeces of the girl as well as puppy dog. Despite antibiotic treatment, symptoms and shedding of the organism in the faeces endured during a 2 month period. PMID:23955982

  12. Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma

    PubMed Central

    Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

    2016-01-01

    Purpose The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. Patients and Methods A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. Results In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43–0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38–0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. Conclusions In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of

  13. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial

    PubMed Central

    Oza, Amit M; Cook, Adrian D; Pfisterer, Jacobus; Embleton, Andrew; Ledermann, Jonathan A; Pujade-Lauraine, Eric; Kristensen, Gunnar; Carey, Mark S; Beale, Philip; Cervantes, Andrés; Park-Simon, Tjoung-Won; Rustin, Gordon; Joly, Florence; Mirza, Mansoor R; Plante, Marie; Quinn, Michael; Poveda, Andrés; Jayson, Gordon C; Stark, Dan; Swart, Ann Marie; Farrelly, Laura; Kaplan, Richard; Parmar, Mahesh K B; Perren, Timothy J

    2015-01-01

    Summary Background The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial. Methods ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I–IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb–IV), with an Eastern Cooperative Oncology Group performance status of 0–2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m2 of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. Findings Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6–56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the

  14. Surviving cancer without compromising aspirations.

    PubMed

    McGregor, Sandra

    2011-07-01

    This short paper is a reflection of how one person coped, survived and grew following numerous metastatic incidences over a 20 year period. Surviving cancer is a complex process but coping with the threat of regular recurrence has required a coping strategy that embraced the disease, set it aside and refused to compromise hopes, dreams and future life. Central to this personal journey has been the need to redefine normality, live with and set aside the fear of future metastases and death and find an answer and meaning in a changing biology, increased morbidity and possible mortality. This paper contends that not compromising the direction of travel and being able to focus on a career has ensured that survival was valuable and valued. A working environment in which students' problems have been immediate has produced different stressors. These have ultimately forced personal worries to be set aside, while living with cancer has become normal and accepted. PMID:21514884

  15. Correlates to survival of juvenile sea otters in Prince William Sound, Alaska, 1992-1993

    USGS Publications Warehouse

    Ballachey, B.E.; Bodkin, J.L.; Howlin, S.; Doroff, A.M.; Rebar, A.H.

    2003-01-01

    We estimated survival of sea otters (Enhydra lutris) for 1 year post weaning during 1992-1993 in Prince William Sound (PWS), location of the 1989 Exxon Valdez oil spill. We sampled 38 pups in eastern PWS (EPWS), an unoiled area occupied by sea otters for 25 years. We compared survival between areas, sexes, and condition groups. We also examined the relation of blood parameters to survival. Survival was estimated at 0.74 in EPWS and 0.52 in WPWS. Female survival was 0.86 in EPWS and 0.64 in WPWS, whereas male survival was lower, 0.61 in EPWS and 0.44 in WPWS. Sea otters from EPWS were in better condition (mass/length) than WPWS sea otters. Pups in better condition had higher survival in EPWS but not in WPWS. Foraging success was greater in EPWS than in WPWS, consistent with either an effect of length of occupation or the effects of oil on the prey base or a combination of these effects. Area differences in blood parameters suggested liver damage in WPWS sea otters, perhaps resulting from continued exposure to oil. Thus, both length of occupation and oiling history likely influenced juvenile survival in PWS.

  16. Lung cancer survival in Norway, 1997-2011: from nihilism to optimism.

    PubMed

    Nilssen, Yngvar; Strand, Trond Eirik; Fjellbirkeland, Lars; Bartnes, Kristian; Møller, Bjørn

    2016-01-01

    We examine changes in survival and patient-, tumour- and treatment-related factors among resected and nonresected lung cancer patients, and identify subgroups with the largest and smallest survival improvements.National population-based data from the Cancer Registry of Norway, Statistics Norway and the Norwegian Patient Register were linked for lung cancer patients diagnosed during 1997-2011. The 1- and 5-year relative survival were estimated, and Cox proportional hazard regression, adjusted for selected patient characteristics, was used to assess prognostic factors for survival in lung cancer patients overall and stratified by resection status.We identified 34 157 patients with lung cancer. The proportion of histological diagnoses accompanied by molecular genetics testing increased from 0% to 26%, while those accompanied by immunohistochemistry increased from 8% to 26%. The 1-year relative survival among nonresected and resected patients increased from 21.7% to 34.2% and 75.4% to 91.5%, respectively. The improved survival remained significant after adjustment for age, sex, stage and histology. The largest improvements in survival occurred among resected and adenocarcinoma patients, while patients ≥80 years experienced the smallest increase.Lung cancer survival has increased considerably in Norway. The explanation is probably multifactorial, including improved attitude towards diagnostic work-up and treatment, and more accurate diagnostic testing that allows for improved selection for resection and improved treatment options. PMID:26541525

  17. Survival of Sami cancer patients

    PubMed Central

    Soininen, Leena; Pokhrel, Arun; Dyba, Tadek; Pukkala, Eero; Hakulinen, Timo

    2012-01-01

    Objectives The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30) and for non-Sami 1.02 (0.86–1.20), indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland. PMID:22765936

  18. Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer

    PubMed Central

    ZHAO, YA-NAN; HE, DONG-NING; WANG, YA-DI; LI, JUN-JIE; HA, MIN-WEN

    2016-01-01

    The human major vault protein (MVP) has been linked to the development of multidrug resistance in cancer cells, and overexpression of MVP has been observed in ovarian cancer tissues. The aim of the present study was to investigate the association between single nucleotide polymorphisms (SNPs) in the MVP gene and the tumor response to platinum-based chemotherapy and survival of patients affected by epithelial ovarian cancer (EOC), in addition to confirm whether tetra-primer amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) is an accurate genotyping method. For this purpose, two polymorphisms in the MVP gene, namely reference SNP (rs)1057451 and rs4788186, were selected from the data obtained by the International haplotype map (HapMap) Project regarding Chinese Han population, and were evaluated by tetra-primer ARMS-PCR. Upon validation by DNA sequencing, the association of these polymorphisms with platinum resistance, progression-free survival (PFS) and overall survival (OS) in patients with EOC was assessed. The results of tetra-primer ARMS-PCR were in agreement with those derived from DNA sequencing. No significant differences were observed between platinum-sensitive and platinum-resistant cohorts in terms of allele and genotype distribution of these two polymorphisms in the MVP gene, which were not associated with PFS or OS. However, a trend toward prolonged PFS was observed in patients carrying the heterozygous AG allele at the rs4788186 locus. These results suggest that rs1057451 and rs4788186 variants in the MVP gene are not associated with favorable therapeutic response to platinum or longer survival in Chinese Han patients affected by EOC. In addition, the data of the present study confirm that tetra-primer ARMS-PCR is a trustworthy and economical genotyping method. PMID:27073578

  19. Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S. Galbreath, Robert W.; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Lief, Jonathan H.; Adamovich, Edward

    2009-07-15

    Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined for each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.

  20. A 1-year Aspergillus terreus surveillance study at the University Hospital of Innsbruck: molecular typing of environmental and clinical isolates.

    PubMed

    Blum, G; Perkhofer, S; Grif, K; Mayr, A; Kropshofer, G; Nachbaur, D; Kafka-Ritsch, R; Dierich, M P; Lass-Flörl, C

    2008-12-01

    Aspergillus terreus appears to have become an increasingly frequent cause of opportunistic infections in the University Hospital of Innsbruck (UHI) and is of serious concern because of in vivo and in vitro resistance to amphotericin B. In order to determine the possible relationship between environmental contamination by A. terreus and the occurrence of invasive aspergillosis, a 1-year prospective study (2004-2005) was carried out in the UHI. Isolates obtained from air samples of various high-risk settings and those from surveillance cultures of proven and probable aspergillosis (EORTC/MSG criteria) were examined by genotyping. Within 1 year, 34 and 15 A. terreus isolates were collected from the environment and from patients, respectively. Genotypic analysis with rapid amplification of polymorphic DNA (RAPD) PCR and the combination of three different primers (R108, CII, P4) revealed 46 distinct genotypic profiles (types 1-46). No strain similarity was detected among and within the patients and environmental areas, indicating a great genomic diversity in A. terreus, which is common in the environment of Innsbruck and a source of invasive infections in immunosuppressed patients. Genotypical diversity was found in clinical and environmental A. terreus isolates. PMID:19076844

  1. Outcomes of minimally 1 year follow-up for the arthroscopic Remplissage technique with Hill–Sachs lesion

    PubMed Central

    Ko, Sang-Hun; Shin, Seung-Myeong; Jo, Beom-Geon

    2013-01-01

    Purpose We evaluated minimal 1 year follow-up results for the Remplissage technique to fill a Hill–Sachs lesion with anterior instability. Methods The subjects were 12 patients, who could be followed-up for more than 12 months after the ”Remplissage” procedures in our hospital from August 2008 to May 2010. Their mean age was 28.6 years old and the mean follow-up was 19 months. The evaluations included the ROM, the ASES score, the KSSI score, the ROWE score and postoperative MRI. Results On the postoperative functional evaluation after an average 16 months, the ASES score improved 51.4 in preoperative to 86.6 in postoperatively, the KSSI score improved from 46.6 preoperatively to 84.9 postoperatively and the ROWE score improved from 43.6 preoperatively to 91.4 postoperatively. After an average 14 months for all the cases, the range of movement was nearly in the normal range which is 174.3 ± 5.04 (170–180) degrees in foreward flexion, and 56.4 ± 9.60 (50–60) degrees in external rotation. Conclusion For recurrent shoulder instability with a large Hill–Sachs lesion, the Remplissage technique has a good outcome after more than 1 year follow-up in terms of shoulder stability, and the clinical and functional results. Level of evidence Level IV, therapeutic case series PMID:24403747

  2. Bone Mineral Density at Diagnosis of Celiac Disease and after 1 Year of Gluten-Free Diet

    PubMed Central

    Pantaleoni, Stefano; Luchino, Massimo; Adriani, Alessandro; Pellicano, Rinaldo; Stradella, Davide; Ribaldone, Davide Giuseppe; Sapone, Nicoletta; Isaia, Gian Carlo; Di Stefano, Marco; Astegiano, Marco

    2014-01-01

    Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <−1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients. PMID:25379519

  3. Working Memory Deficit as a Risk Factor for Severe Apathy in Schizophrenia: A 1-Year Longitudinal Study.

    PubMed

    Raffard, Stéphane; Gutierrez, Laure-Anne; Yazbek, Hanan; Larue, Aurore; Boulenger, Jean-Philippe; Lançon, Christophe; Benoit, Michel; Faget, Catherine; Norton, Joanna; Capdevielle, Delphine

    2016-05-01

    Apathy, described as impaired motivation and goal-directed behavior, is a common yet often overlooked multidimensional psychopathological state in schizophrenia. Its underlying cognitive processes remain largely unexplored. Data was drawn from a longitudinal hospital study of patients with a DSM-IV diagnosis of schizophrenia; 137 (82.5%) participated at the 1-month follow-up and 81 (59.1%) at the 1-year follow-up. Apathy was assessed with the Lille Apathy Rating Scale, validated in French and in schizophrenia. Severe apathy, overall (total score > -13) and on 4 previously identified distinct dimensions, was considered. Episodic verbal learning was assessed with the California Verbal Learning Test, executive functioning with the Trail Making Test, the Six Element Test and the Stop Signal Paradigm and working memory with the Letter-Number Sequencing Test. After controlling for confounding variables, only episodic verbal learning was associated with severe overall apathy in the cross-sectional study. At 1 year, working memory was associated with an increased risk of severe overall apathy, adjusting for baseline apathy. Using a dimensional approach to apathy, specific types of cognition were found to be associated with specific dimensions of apathy. Our findings confirm the need for a multidimensional approach of negative symptoms in schizophrenia. Moreover, cognitive functioning could be a risk factor for developing severe apathy. Cognitive remediation may thus be a useful non-pharmacological intervention for treating apathy in schizophrenia patients. PMID:26834026

  4. Cognitive function, social functioning and quality of life in first-episode psychosis: A 1-year longitudinal study.

    PubMed

    Popolo, Raffaele; Vinci, Giancarlo; Balbi, Andrea

    2010-03-01

    Abstract Objective. The majority of patients with schizophrenia have cognitive deficits early in the disease. We evaluated the relationship between cognitive function, social functioning and quality of life in patients with first-episode psychosis. Methods. This was a longitudinal study in 15 patients aged 18-30 years who had recently experienced a first psychotic episode and were treated with the atypical antipsychotic aripiprazole, cognitive-behavioural therapy, psycho-educational sessions, family supportive sessions and social interventions. Patients were evaluated at baseline and after 1 year. Cognitive assessment included attention, memory, language skills and problem solving. Social functioning, quality of life, and psychopathological evaluation were performed with validated tools. Results. At baseline, patients had a severe impairment of social functioning and a low quality of life, while a specific pattern of cognitive functions was not identified. After 1-year, we observed a significant improvement in social functioning and quality of life, without a significant decrease in cognitive function. Conclusion. Contrary to previous findings, we found that social functioning and quality of life are related, but independent of cognitive impairment. The use of antipsychotic agents that do not interefere with cognitive function plus psychological assistance is a valuable treatment approach in patients with first-episode schizophrenia. PMID:24917230

  5. Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet.

    PubMed

    Pantaleoni, Stefano; Luchino, Massimo; Adriani, Alessandro; Pellicano, Rinaldo; Stradella, Davide; Ribaldone, Davide Giuseppe; Sapone, Nicoletta; Isaia, Gian Carlo; Di Stefano, Marco; Astegiano, Marco

    2014-01-01

    Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <-1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients. PMID:25379519

  6. Self-management of chronic pain in Malaysian patients: effectiveness trial with 1-year follow-up.

    PubMed

    Cardosa, Mary; Osman, Zubaidah Jamil; Nicholas, Michael; Tonkin, Lois; Williams, Amanda; Abd Aziz, Khuzaimah; Mohd Ali, Ramli; Dahari, Norhana Mohd

    2012-03-01

    Self-management of chronic illnesses has been widely recognised as an important goal on quality of life, health service utilisation and cost grounds. This study describes the first published account on the application of this approach to people suffering from chronic pain conditions in a Southeast Asian country, Malaysia. A heterogeneous sample of chronic pain patients in Malaysia attended a 2-week cognitive-behavioural pain management programme (PMP) aimed at improving daily functional activities and general psychological well-being. Complete datasets from 70 patients out of 102 patients who attended 11 programmes conducted from 2002 to 2007, as well as the 1-month and 1-year follow-up sessions at the hospital clinic, are reported. The pre- to post-treatment results on self-report measures indicate that significant gains were achieved on the dimensions of pain, disability and psychological well-being. These gains were maintained at both 1-month and 1-year follow-ups. The results mirror those reported from similar interventions in Europe and North America and indicate the concept of self-management of a chronic illness is acceptable and meaningful to Asian patients. Importantly, the achieved outcomes were independent of gender and ethnic group status. PMID:22448204

  7. Management and 1-year outcomes of patients with atrial fibrillation in the Middle East: Gulf survey of atrial fibrillation events.

    PubMed

    Zubaid, Mohammad; Rashed, Wafa A; Alsheikh-Ali, Alawi A; Al-Zakwani, Ibrahim; AlMahmeed, Wael; Shehab, Abdullah; Sulaiman, Kadhim; Qudaimi, Ahmed Al; Asaad, Nidal; Amin, Haitham

    2015-05-01

    We describe management and outcomes of patients with nonvalvular atrial fibrillation (AF) in the Middle East. Consecutive patients with AF presenting to emergency departments (EDs) were prospectively enrolled. Among 1721 patients with nonvalvular AF, mean age was 59 ± 16 years and 44% were women. Comorbidities were common such as hypertension (59%), diabetes (33%), and coronary artery disease (33%). Warfarin was not prescribed to 40% of patients with Congestive heart failure, Hypertension, Age, Diabetes mellitus, Stroke/TIA2 score of ≥2. One-year rates of stroke/transient ischemic attack (TIA) and all-cause mortality were 4.2% and 15.3%, respectively. Warfarin use at hospital-ED discharge was independently associated with lower 1-year rate of stroke/TIA (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17-0.85; P = .015) and all-cause mortality (OR, 0.51; 95% CI, 0.32-0.83; P = .006). Prior history of heart failure and peripheral vascular disease was independent mortality predictors. Our patients are relatively young with significant cardiovascular risk. Their anticoagulation treatment is suboptimal, and 1-year all-cause mortality and stroke/TIA event rates are relatively high. PMID:24904179

  8. Trajectories of Depressive Symptomatology in Rural Memory Clinic Patients between Baseline Diagnosis and 1-Year Follow-Up

    PubMed Central

    Kosteniuk, Julie G.; Morgan, Debra G.; O'Connell, Megan E.; Kirk, Andrew; Crossley, Margaret; Stewart, Norma J.; Karunanayake, Chandima P.

    2016-01-01

    Background/Aims To investigate the prevalence and trajectories of depressive symptomatology at 1-year follow-up, and the severity of depressive symptoms, by dementia diagnostic group, as well as to determine the predictors of depressive symptomatology at 1-year follow-up. Methods In rural and remote patients of an interdisciplinary memory clinic between 2004 and 2014, 144 patients diagnosed with no cognitive impairment (NCI), mild cognitive impairment, dementia due to Alzheimer's disease (AD), or non-AD dementia completed the Center for Epidemiologic Studies of Depression Scale to assess depressive symptomatology at both time points. Results Among patients with data at both time points, persistence of depressive symptomatology at follow-up occurred in 22.2%, remission in 17.4%, incidence in 13.2%, and absence in 47.2%. The prevalence of depressive symptomatology at baseline and persistence at follow-up were significantly greater in the NCI group than in the other diagnostic groups, but there were no differences in severity. Depressive symptomatology at follow-up was independently associated with depressive symptomatology, lower independence in activities of daily living, and lower self-rating of memory at baseline, as well as with decreased independence in activities of daily living between time points. Conclusion Future studies should further examine short-term postdiagnostic trajectories in depressive symptomatology in multiple dementia diagnostic groups to inform prognoses and treatment decisions. PMID:27350776

  9. Survival Benefit for Pediatric Patients With Recurrent Ependymoma Treated With Reirradiation

    SciTech Connect

    Bouffet, Eric; Ballourah, Walid; Bartels, Ute K.; Tsangaris, Elena; Huang, Annie; Mabbot, Donald J.; Laperriere, Normand; Tabori, Uri

    2012-08-01

    Purpose: The outcome of recurrent ependymoma in children is dismal. Reirradiation has been proposed as an effective modality for ependymoma at relapse. However, the toxicity and outcome benefits of this approach have not been well established. Methods and Materials: We conducted a retrospective population-based study of all patients with recurrent ependymoma treated between 1986 and 2010 in our institution. Demographic, treatment, and outcome data were analyzed for the entire cohort. Results: Of 113 patients with intracranial ependymoma, 47 patients relapsed. At the time of relapse, 29 patients were treated with surgical resection and/or chemotherapy, and 18 patients received full-dose ({>=}54 Gy focal and/or craniospinal) reirradiation with or without surgery at recurrence. Reirradiation was tolerated well with no severe acute complications noticed. Three-year overall survival was 7% {+-} 6% and 81% {+-} 12% for nonreirradiated and reirradiated patients, respectively (p < 0.0001). Time to second progression after reirradiation was significantly longer than time to first progression. This surprising phenomenon was associated with improved progression-free survival for tumors with evidence of DNA damage (n = 15; p = 0.002). At a mean follow-up of 3.73 years, only 2/18 patients had endocrine dysfunction, and 1 patient required special education support. However, a decline in intellectual function from pre- to postreirradiation assessment was observed. Conclusions: Reirradiation is an effective treatment that may change the natural history of recurrent ependymoma in children. However, this change may be associated with increased neurocognitive toxicity. Additional follow-up is needed to determine the risk of late recurrence, secondary radiation-induced tumors, and long-term functional outcome of these patients.

  10. Survival analysis in patients with newly diagnosed glioblastoma using pre- and postradiotherapy MR spectroscopic imaging†

    PubMed Central

    Li, Yan; Lupo, Janine M.; Parvataneni, Rupa; Lamborn, Kathleen R.; Cha, Soonmee; Chang, Susan M.; Nelson, Sarah J.

    2013-01-01

    Background The objective of this study was to examine the predictive value of parameters of 3D 1H magnetic resonance spectroscopic imaging (MRSI) prior to treatment with radiation/chemotherapy (baseline) and at a postradiation 2-month follow-up (F2mo) in relationship to 6-month progression-free survival (PFS6) and overall survival (OS). Methods Sixty-four patients with newly diagnosed glioblastoma multiforme (GBM) being treated with radiation and concurrent chemotherapy were involved in this study. Evaluated were metabolite indices and metabolite ratios. Logistic linear regression and Cox proportional hazards models were utilized to evaluate PFS6 and OS, respectively. These analyses were adjusted by age and MR scanner field strength (1.5 T or 3 T). Stepwise regression was performed to determine a subset of the most relevant variables. Results Associated with shorter PFS6 were a decrease in the ratio of N-acetyl aspartate to choline-containing compounds (NAA/Cho) in the region with a Cho-to-NAA index (CNI) >3 at baseline and an increase of the CNI within elevated CNI regions (>2) at F2mo. Patients with higher normalized lipid and lactate at either time point had significantly worse OS. Patients who had larger volumes with abnormal CNI at F2mo had worse PFS6 and OS. Conclusions Our study found more 3D MRSI parameters that predicted PFS6 and OS for patients with GBM than did anatomic, diffusion, or perfusion imaging, which were previously evaluated in the same population of patients. PMID:23393206

  11. Quantification of mutant alleles in circulating tumor DNA can predict survival in lung cancer

    PubMed Central

    Ye, Xin; Bai, Hua; Wang, Zhijie; Sun, Yun; Zhao, Jun; An, Tongtong; Duan, Jianchun; Wu, Meina; Wang, Jie

    2016-01-01

    Purpose We aimed to investigate the feasibility of droplet digital PCR (ddPCR) for the quantitative and dynamic detection of EGFR mutations and next generation sequencing (NGS) for screening EGFR-tyrosine kinase inhibitors (EGFR-TKIs) resistance-relevant mutations in circulating tumor DNA (ctDNA) from advanced lung adenocarcinoma (ADC) patients. Results Detection limit of EGFR mutation in ctDNA by ddPCR was 0.04%. Taking the EGFR mutation in tumor tissue as the golden standard, the concordance of EGFR mutations detected in ctDNA was 74% (54/73). Patients with EGFR mutation in ctDNA (n = 54) superior progression-free survival (PFS, median, 12.6 vs. 6.7 months, P < 0.001) and overall survival (OS, median, 35.6 vs. 23.8 months, P = 0.028) compared to those with EGFR wild type in ctDNA (n = 19). Patients with high EGFR-mutated abundance in ctDNA (> 5.15%) showed better PFS compared to those with low EGFR mutated abundance (≤ 5.15%) (PFS, median, 15.4 vs. 11.1 months, P = 0.021). NGS results showed that 66.6% (8/12) total mutational copy number were elevated and 76.5% (26/34) mutual mutation frequency increased after disease progression. Methods Seventy-three advanced ADC patients with tumor tissues carrying EGFR mutations and their matched pre- and post-EGFR-TKIs plasma samples were enrolled in this study. Absolute quantities of plasma EGFR mutant and wild-type alleles were measured by ddPCR. Multi-genes testing was performed using NGS in 12 patients. Conclusions Dynamic and quantitative analysis of EGFR mutation in ctDNA could guide personalized therapy for advanced ADC. NGS shows good performance in multiple genes testing especially novel and uncommon genes. PMID:26989078

  12. The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma.

    PubMed

    Neidert, Marian C; Hostettler, Isabel C; Burkhardt, Jan-Karl; Mohme, Malte; Held, Ulrike; Kofmehl, Reto; Eisele, Günter; Woernle, Christoph M; Regli, Luca; Bozinov, Oliver

    2016-07-01

    The purpose of the present study is to analyze the impact of intraoperative resection control modalities on overall survival (OS) and progression-free survival (PFS) following gross total resection (GTR) of glioblastoma. We analyzed data of 76 glioblastoma patients (30f, mean age 57.4 ± 11.6 years) operated at our institution between 2009 and 2012. Patients were only included if GTR was achieved as judged by early postoperative high-field MRI. Intraoperative technical resection control modalities comprised intraoperative ultrasound (ioUS, n = 48), intraoperative low-field MRI (ioMRI, n = 22), and a control group without either modality (n = 11). The primary endpoint of our study was OS, and the secondary endpoint was PFS-both analyzed in Kaplan-Meier plots and Cox proportional hazards models. Median OS in all 76 glioblastoma patients after GTR was 20.4 months (95 % confidence interval (CI) 18.5-29.0)-median OS in patients where GTR was achieved using ioUS was prolonged (21.9 months) compared to those without ioUS usage (18.8 months). A multiple Cox model adjusting for age, preop Karnofsky performance status, tumor volume, and the use of 5-aminolevulinic acid showed a beneficial effect of ioUS use, and the estimated hazard ratio was 0.63 (95 % CI 0.31-1.2, p = 0.18) in favor of ioUS, however not reaching statistical significance. A similar effect was found for PFS (hazard ratio 0.59, p = 0.072). GTR of glioblastoma performed with ioUS guidance was associated with prolonged OS and PFS. IoUS should be compared to other resection control devices in larger patient cohorts. PMID:26860420

  13. Physiologic status at 1-year follow-up of obese women engaged in a supervised conditioning program.

    PubMed

    Tanaka, K; Nakadomo, F; Kitao, H; Watanabe, H; Sumida, S

    1991-07-01

    A follow-up study was conducted to re-evaluate a group of obese middle-aged women (n = 13), eight of whom had completed an 18-wk supervised (3 d/wk) plus unsupervised (2 d/wk) conditioning intervention program (at least 90 min per day) as the exercise plus diet group; while five of the remainder served as the control group. Each session had included a 25- to 45-min jog/run at intensities between the heart rate (HR) corresponding to lactate threshold (LT) and that slightly above the HR @ LT. During 1 year following the program, the women participated in self-controlled training such as running, aerobic dancing, or jazz dancing 2.6 +/- 1.1 d/wk. Dietary intake averaged approximately 1736 +/- 152 kcal/d at the pre-treatment, 1404 +/- 124 kcal/d at the post-treatment, and 1645 +/- 147 kcal/d 1 year after the post-treatment. Interestingly however, oxygen uptake corresponding to LT (VO2 @ LT), maximal oxygen uptake (VO2max), weight, systolic blood pressure, and the ratio of high-density lipoprotein cholesterol to total cholesterol (HDLC/TC) observed 1 year after the post-treatment were significantly different from the original pre-treatment and/or mid-treatment values. For instance, the significant 42% increase (14.7 +/- 2.4----21.3 +/- 4.2 ml/kg/min) in VO2 @ LT and 18% increase (0.284 +/- 0.106----0.335 +/- 0.093) in HDLC/TC from the pre-test to post-test were maintained throughout the 1-year follow-up period, suggesting no detrimental effect either on a cardiorespiratory fitness factor or on an anti-atherogenic factor. These findings indicate that physiologic status of obese middle-aged women engaged in a conditioning intervention program may not regress to pre-treatment status for at least one year after completion; provided they continue to participate in a 2.6-d/wk self-controlled training program with dietary intake of 1600-1700 kcal/d. Another interesting finding was that significant relationships existed between individual changes (delta) in training frequency

  14. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    PubMed Central

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  15. Medieval Sport: Quest for Survival.

    ERIC Educational Resources Information Center

    Wiseman, Douglas C.

    Since the Middle Ages, sport has survived because of its masochistic and sadistic components. The Greeks, who organized athletic contests into the Olympic Games in 776 B.C., emphasized the relationship between the mind and the body and fair competition, rather than putting emphasis on winning or losing. The Romans preferred the spectacle of…

  16. Cool echidnas survive the fire.

    PubMed

    Nowack, Julia; Cooper, Christine Elizabeth; Geiser, Fritz

    2016-04-13

    Fires have occurred throughout history, including those associated with the meteoroid impact at the Cretaceous-Palaeogene (K-Pg) boundary that eliminated many vertebrate species. To evaluate the recent hypothesis that the survival of the K-Pg fires by ancestral mammals was dependent on their ability to use energy-conserving torpor, we studied body temperature fluctuations and activity of an egg-laying mammal, the echidna (Tachyglossus aculeatus), often considered to be a 'living fossil', before, during and after a prescribed burn. All but one study animal survived the fire in the prescribed burn area and echidnas remained inactive during the day(s) following the fire and substantially reduced body temperature during bouts of torpor. For weeks after the fire, all individuals remained in their original territories and compensated for changes in their habitat with a decrease in mean body temperature and activity. Our data suggest that heterothermy enables mammals to outlast the conditions during and after a fire by reducing energy expenditure, permitting periods of extended inactivity. Therefore, torpor facilitates survival in a fire-scorched landscape and consequently may have been of functional significance for mammalian survival at the K-Pg boundary. PMID:27075255

  17. GPS survivability - A military overview

    NASA Astrophysics Data System (ADS)

    Burgess, Alan

    The major features contributing to the military survivability of GPS during war are discussed. Possible threats to the various segments of GPS are examined, including the effects of attack, sabotage, and nuclear war. Consideration is given to applicable countermeasures to enable GPS to provide continuous service during war.

  18. Tale of survival tails off.

    PubMed

    Pallarito, K

    1991-02-25

    When Reader's Digest wove the tale of a scrappy rural hospital in Montana that raised enough in donations to keep from going under, it looked like a happy ending. But the last chapter on Sweet Grass Community Hospital's fight to survive is still being written, and it's a cliffhanger. PMID:10109267

  19. Top 10 Staff Survival Tips.

    ERIC Educational Resources Information Center

    O'Brien, Laurie

    1995-01-01

    Tips for camp staff on how to survive summer camp include not giving campers sugary drinks before bedtime, setting behavior limits with campers, setting an example by following camp rules, getting enough rest, being fair and consistent, controlling anger, being accountable for actions, asking questions, and being flexible. (LP)

  20. Wilderness Emergency: Surviving the Unexpected.

    ERIC Educational Resources Information Center

    Fear, Gene

    In any unexpected survival experience, one must accept the situation with just what one has at the moment it happens, where it happens, and how it happens. Problem solving must be based on known body enemies that threaten life, their priority of influence, and their severity of threat to life. Solutions will depend on the body's energy supply,…

  1. Wilderness Survival and Outdoor Education.

    ERIC Educational Resources Information Center

    Ball, Matt

    Outdoor education is often delivered through games and activities such as nature hikes or observing an ecosystem within a 1-foot circle on the ground. Often, participants look closely at the earth only for that brief moment. Wilderness survival is another way to teach about the outdoors. It offers skills that encourage participants to become more…

  2. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial

    PubMed Central

    Rule, Simon; Smith, Paul; Johnson, Peter W.M.; Bolam, Simon; Follows, George; Gambell, Joanne; Hillmen, Peter; Jack, Andrew; Johnson, Stephen; Kirkwood, Amy A; Kruger, Anton; Pocock, Christopher; Seymour, John F.; Toncheva, Milena; Walewski, Jan; Linch, David

    2016-01-01

    Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network. PMID:26611473

  3. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial.

    PubMed

    Rule, Simon; Smith, Paul; Johnson, Peter W M; Bolam, Simon; Follows, George; Gambell, Joanne; Hillmen, Peter; Jack, Andrew; Johnson, Stephen; Kirkwood, Amy A; Kruger, Anton; Pocock, Christopher; Seymour, John F; Toncheva, Milena; Walewski, Jan; Linch, David

    2016-02-01

    Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network. PMID:26611473

  4. Corticosteroids compromise survival in glioblastoma.

    PubMed

    Pitter, Kenneth L; Tamagno, Ilaria; Alikhanyan, Kristina; Hosni-Ahmed, Amira; Pattwell, Siobhan S; Donnola, Shannon; Dai, Charles; Ozawa, Tatsuya; Chang, Maria; Chan, Timothy A; Beal, Kathryn; Bishop, Andrew J; Barker, Christopher A; Jones, Terreia S; Hentschel, Bettina; Gorlia, Thierry; Schlegel, Uwe; Stupp, Roger; Weller, Michael; Holland, Eric C; Hambardzumyan, Dolores

    2016-05-01

    Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects. The effects of corticosteroids such as dexamethasone on cell growth in glioma models and on patient survival have remained controversial. We performed a retrospective analysis of glioblastoma patient cohorts to determine the prognostic role of steroid administration. A disease-relevant mouse model of glioblastoma was used to characterize the effects of dexamethasone on tumour cell proliferation and death, and to identify gene signatures associated with these effects. A murine anti-VEGFA antibody was used in parallel as an alternative for oedema control. We applied the dexamethasone-induced gene signature to The Cancer Genome Atlas glioblastoma dataset to explore the association of dexamethasone exposure with outcome. Mouse experiments were used to validate the effects of dexamethasone on survival in vivo Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts. A dexamethasone-associated gene expression signature correlated with shorter survival in The Cancer Genome Atlas patient dataset. In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy. Conversely, anti-VEGFA antibody decreased proliferation and increased tumour cell death, but did not affect survival when combined with radiotherapy. Clinical and mouse experimental data suggest that corticosteroids may decrease the effectiveness of treatment and shorten

  5. Challenging Gait Conditions Predict 1-Year Decline in Gait Speed in Older Adults With Apparently Normal Gait

    PubMed Central

    Perera, Subashan; VanSwearingen, Jessie M.; Hile, Elizabeth S.; Wert, David M.; Studenski, Stephanie A.

    2011-01-01

    Background Mobility often is tested under a low challenge condition (ie, over a straight, uncluttered path), which often fails to identify early mobility difficulty. Tests of walking during challenging conditions may uncover mobility difficulty that is not identified with usual gait testing. Objective The purpose of this study was to determine whether gait during challenging conditions predicts decline in gait speed over 1 year in older people with apparently normal gait (ie, gait speed of ≥1.0 m/s). Design This was a prospective cohort study. Methods Seventy-one older adults (mean age=75.9 years) with a usual gait speed of ≥1.0 m/s participated. Gait was tested at baseline under 4 challenging conditions: (1) narrow walk (15 cm wide), (2) stepping over obstacles (15.24 cm [6 in] and 30.48 cm [12 in]), (3) simple walking while talking (WWT), and (4) complex WWT. Usual gait speed was recorded over a 4-m course at baseline and 1 year later. A 1-year change in gait speed was calculated, and participants were classified as declined (decreased ≥0.10 m/s, n=18), stable (changed <0.10 m/s, n=43), or improved (increased ≥0.10 m/s, n=10). Analysis of variance was used to compare challenging condition cost (usual − challenging condition gait speed difference) among the 3 groups. Results Participants who declined in the ensuing year had a greater narrow walk and obstacle walk cost than those who were stable or who improved in gait speed (narrow walk cost=0.43 versus 0.33 versus 0.22 m/s and obstacle walk cost=0.35 versus 0.26 versus 0.13 m/s). Simple and complex WWT cost did not differ among the groups. Limitations The participants who declined in gait speed over time walked the fastest, and those who improved walked the slowest at baseline; thus, the potential contribution of regression to the mean to the findings should not be overlooked. Conclusions In older adults with apparently normal gait, the assessment of gait during challenging conditions appears to uncover

  6. Factors associated with postoperative complications and 1-year mortality after surgery for colorectal cancer in octogenarians and nonagenarians

    PubMed Central

    Kim, Young Wan; Kim, Ik Yong

    2016-01-01

    Purpose To identify the factors affecting 30-day postoperative complications and 1-year mortality after surgery for colorectal cancer in octogenarians and nonagenarians. Methods Between 2005 and 2014, a total of 204 consecutive patients aged ≥80 years who underwent major colorectal surgery were included. Results One hundred patients were male (49%) and 52 patients had American Society of Anesthesiologists (ASA) score ≥3 (25%). Combined surgery was performed in 32 patients (16%). Postoperative complications within 30 days after surgery occurred in 54 patients (26%) and 30-day mortality occurred in five patients (2%). Independent risk factors affecting 30-day postoperative complications were older age (≥90 years, hazard ratio [HR] with 95% confidence interval [CI] =4.95 [1.69−14.47], P=0.004), an ASA score ≥3 (HR with 95% CI =4.19 [1.8−9.74], P=0.001), performance of combined surgery (HR with 95% CI =3.1 [1.13−8.46], P=0.028), lower hemoglobin level (<10 g/dL, HR with 95% CI =7.56 [3.07−18.63], P<0.001), and lower albumin level (<3.4 g/dL, HR with 95% CI =3.72 [1.43−9.69], P=0.007). An ASA score ≥3 (HR with 95% CI =2.72 [1.15−6.46], P=0.023), tumor-node-metastasis (TNM) stage IV (HR with 95% CI =3.47 [1.44−8.39], P=0.006), and occurrence of postoperative complications (HR with 95% CI =4.42 [1.39−14.09], P=0.012) were significant prognostic factors for 1-year mortality. Conclusion Patient-related factors (older age, higher ASA score, presence of anemia, and lower serum albumin) and procedure-related factors (performance of combined surgical procedure) increased postoperative complications. Avoidance of 30-day postoperative complications may decrease 1-year mortality. PMID:27279741

  7. Plasticity and rectangularity in survival curves

    PubMed Central

    Weon, Byung Mook; Je, Jung Ho

    2011-01-01

    Living systems inevitably undergo a progressive deterioration of physiological function with age and an increase of vulnerability to disease and death. To maintain health and survival, living systems should optimize survival strategies with adaptive interactions among molecules, cells, organs, individuals, and environments, which arises plasticity in survival curves of living systems. In general, survival dynamics in a population is mathematically depicted by a survival rate, which monotonically changes from 1 to 0 with age. It would be then useful to find an adequate function to describe complicated survival dynamics. Here we describe a flexible survival function, derived from the stretched exponential function by adopting an age-dependent shaping exponent. We note that the exponent is associated with the fractal-like scaling in cumulative mortality rate. The survival function well depicts general features in survival curves; healthy populations exhibit plasticity and evolve towards rectangular-like survival curves, as examples in humans or laboratory animals. PMID:22355622

  8. AIAA Survivability Technical Committee Draft

    NASA Technical Reports Server (NTRS)

    Shipman, Jim; Williamson, Joel

    1997-01-01

    A relatively new area of interest in aerospace systems survivability is the growing threat of spacecraft penetration by orbital debris. Orbital debris, or "space junk", is composed of the man-made remnants of non-functioning spacecraft still orbiting the Earth. NASA estimates that there are currently over 100,000 orbital debris particles 1 centimeter in diameter or larger that cannot be tracked by existing radar, with the population growing at approximately 4% per year in low earth orbits. With an average velocity of over 8.7 km/sec, these projectiles can penetrate and disable many vulnerable spacecraft systems. Since the likelihood of spacecraft penetration increases with spacecraft surface area, large spacecraft (such as the International Space Station) and communication satellite fleets (such as Iridium) have begun to adopt survivability enhancement strategies similar to those employed by combat aircraft. Collision avoidance maneuvers are commonly practiced by the Space Shuttle and are planned by the International Space Station to decrease their susceptibility to impact by trackable orbital debris; likewise, improved shielding, internal equipment placement, and improved crew operations following penetration can reduce the vulnerability of spacecraft to loss following orbital debris impact. Computer simulations such as the Manned Spacecraft and Crew Survivability (MSCSurv) program at the NASA-Marshall Space Flight Center have recently been developed to quantify and reduce the likelihood of crew or spacecraft loss following orbital debris penetration. The AIAA Survivability Technical Committee is working to enable the transfer of military-developed survivability technologies to help the aerospace industry cope with this growing threat.

  9. Successful Endosonography-Guided Drainage of an Intra-Abdominal Abscess in a 1-Year-Old Infant

    PubMed Central

    Ito, Yukiko; Isayama, Hiroyuki; Nakai, Yousuke; Umefune, Gyoutane; Sato, Tatsuya; Nakahara, Saori; Suwa, Junko; Kato, Keiichi; Nakata, Ryo

    2016-01-01

    Endoscopic ultrasound (EUS)-guided intervention has been established as a safe, effective and minimally invasive procedure for various diseases in adults, but there have been limited reports in pediatric patients. Herein, we report our experience with successful EUS-guided drainage of an intra-abdominal abscess in a 1-year-old infant concomitant with disseminated intravascular coagulation. The abscess was punctured via the stomach using a standard, convex-type echoendoscope, and the patient’s condition improved after naso-cystic catheter placement. Although the clinical course was complicated by delayed hemorrhage from the puncture site, the bleeding was successfully managed by endoscopic hemostasis using a standard forward-viewing endoscope. PMID:27114437

  10. Extensive 1-year survey of trace elements and compounds in the airborne suspended particulate matter in Cleveland, Ohio

    NASA Technical Reports Server (NTRS)

    King, R. B.; Fordyce, J. S.; Antoine, A. C.; Leibecki, H. F.; Neustadter, H. E.; Sidik, S. M.

    1976-01-01

    Concentrations of 75 chemical constituents in the airborne particulate matter were measured in Cleveland, Ohio, during 1971 and 1972. Values covering a 1-year period (45 to 50 sampling days) at each of 16 sites are presented for 60 elements. A lesser number of values is given for sulfate, nitrate, fluoride, acidity, 10 polynuclear aromatic hydrocarbon compounds, and the aliphatic hydrocarbon compounds as a group. Methods used included instrumental neutron activation, emission spectroscopy, gas chromatography, combustion techniques, and colorimetry. Uncertainties in the concentrations associated with the sampling procedures, the analysis methods, the use of several analytical facilities, and samples with concentrations below the detection limits are evaluated in detail. The data is discussed in relation to other studies and source origins. The trace constituent concentrations as a function of wind direction are used to suggest a practical method for air pollution source identification.

  11. The Chicago Parent Program: Comparing 1-Year Outcomes for African American and Latino Parents of Young Children

    PubMed Central

    Breitenstein, Susan M.; Gross, Deborah; Fogg, Louis; Ridge, Alison; Garvey, Christine; Julion, Wrenetha; Tucker, Sharon

    2012-01-01

    Data were merged from two prevention randomized trials testing 1-year outcomes of a parenting skills program, the Chicago Parent Program (CPP), and comparing its effects for African-American (n=291) versus Latino (n=213) parents and their preschool children. Compared to controls, intervention parents had improved self-efficacy, used less corporal punishment and more consistent discipline, and demonstrated more positive parenting. Intervention children had greater reductions in behavior problems based on parent-report, teacher-report, and observation. Although improvements from CPP were evident for parents in both racial/ethnic groups, Latino parents reported greater improvements in their children’s behavior and in parenting self-efficacy but exhibited greater decreases in praise. Findings support the efficacy of the CPP for African American and Latino parents and young children from low-income urban communities. PMID:22622598

  12. Risk and protective factors for peer victimization: a 1-year follow-up study of urban American students.

    PubMed

    Karlsson, Elisabeth; Stickley, Andrew; Lindblad, Frank; Schwab-Stone, Mary; Ruchkin, Vladislav

    2014-09-01

    This study examined whether internalizing problems, parental warmth and teacher support were associated with adolescents' experience of future peer victimization in school. Data were drawn from two rounds of the longitudinal Social and Health Assessment (SAHA). Study subjects comprised 593 US urban adolescents (aged 13.8 ± 0.8 years; 56 % female). Results showed that there was a substantial degree of continuity in peer victimization over a 1-year period. The presence of internalizing (anxiety, depressive and somatic) symptoms at baseline was associated with an increased risk of peer victimization over time. Both parental warmth and teacher support were uniquely associated with a lower risk for peer victimization. Implications of these findings for prevention efforts are discussed. PMID:24346176

  13. The Chicago Parent Program: comparing 1-year outcomes for African American and Latino parents of young children.

    PubMed

    Breitenstein, Susan M; Gross, Deborah; Fogg, Louis; Ridge, Alison; Garvey, Christine; Julion, Wrenetha; Tucker, Sharon

    2012-10-01

    Data were merged from two prevention randomized trials testing 1-year outcomes of a parenting skills program, the Chicago Parent Program (CPP) and comparing its effects for African-American (n = 291) versus Latino (n = 213) parents and their preschool children. Compared to controls, intervention parents had improved self-efficacy, used less corporal punishment and more consistent discipline, and demonstrated more positive parenting. Intervention children had greater reductions in behavior problems based on parent-report, teacher-report, and observation. Although improvements from the CPP were evident for parents in both racial/ethnic groups, Latino parents reported greater improvements in their children's behavior and in parenting self-efficacy but exhibited greater decreases in praise. Findings support the efficacy of the CPP for African American and Latino parents and young children from low-income urban communities. PMID:22622598

  14. Submaxillary gland androgen-regulated protein 3A expression is an unfavorable risk factor for the survival of oropharyngeal squamous cell carcinoma patients after surgery.

    PubMed

    Koffler, Jennifer; Holzinger, Dana; Sanhueza, Gustavo Acuña; Flechtenmacher, Christa; Zaoui, Karim; Lahrmann, Bernd; Grabe, Niels; Plinkert, Peter K; Hess, Jochen

    2013-03-01

    Recently, increased expression of the submaxillary gland androgen-regulated protein 3A (SMR3A) was found in recurrent tumors of an orthotopic floor-of-mouth mouse tumor model after surgery. However, SMR3A expression in the pathogenesis of human malignancy and its correlation with the clinical outcome have not been addressed so far. We analyzed tissue microarrays with specimens from oropharyngeal squamous cell carcinoma (OPSCC) patients (n = 157) by immunohistochemistry and compared SMR3A expression with clinical and pathological features by statistical analysis. Strong SMR3A expression was found in almost 36 % of all primary OPSCCs. Although, SMR3A protein levels were not associated with any clinical or histopathological feature tested, univariate Kaplan-Meier analysis revealed a significant correlation between high SMR3A protein expression and poor progression-free (p = 0.02) and overall survival (p = 0.03). Furthermore, high SMR3A expression was an independent marker for poor clinical outcome [HR (SMR3A(high) vs. SMR3(low)) = 2.32; 95 % CI = 1.03-5.23] concerning overall survival in a multivariate analysis of OPSCC patients with surgery as primary therapy (n = 100). Our data demonstrate for the first time increased SMR3A protein expression in the pathogenesis of OPSCC, which serves as an unfavorable risk factor for patient survival. PMID:23053383

  15. A Prospective Study Assessing Tumour Response, Survival, and Palliative Care Outcomes in Patients with HIV-Related Kaposi's Sarcoma at Queen Elizabeth Central Hospital, Blantyre, Malawi

    PubMed Central

    Francis, H.; Bates, M. J.; Kalilani, L.

    2012-01-01

    Background. Human-Immunodeficiency-Virus- (HIV-) related Kaposi's sarcoma (KS) has a high prevalence in Africa; however, there is minimal published data on treatment and outcomes in this population. Objective and Design. This was a prospective study of 50 patients, aiming to assess the impact of vincristine therapy on tumour response and survival and to assess palliative care outcomes in patients with HIV-related KS. Methods. 50 consecutive patients were recruited during 2008. Vincristine therapy and highly active antiretroviral therapy (HAART) were given. Tumour response, survival, and chemotherapy-related toxicities were documented. Palliative care outcomes were assessed using the African Palliative Care Association (APCA) Palliative Outcome Scale (POS). Results. The majority of patients were male, and the median age was 33 years. At baseline assessment, the median CD4 T-cell count was 263, and 50% patients had evidence of peripheral neuropathy. The overall response rate was 64% at 6 weeks, and median progression-free survival was 30 weeks. Treatment was generally well tolerated, with peripheral neuropathy the main dose-limiting toxicity. Conclusion. The combination of vincristine and HAART is feasible and effective in a low resource setting, although peripheral neuropathy is a dose-limiting factor. This patient group carries a high mortality and as such adequate access to palliative care is crucial. PMID:22496970

  16. Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

    SciTech Connect

    Zhang, Xi-Mei; Li, Ye-Xiong; Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua; Zhou, Li-Qiang; Liu, Xin-Fan; Yu, Zi-Hao

    2013-03-15

    Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.

  17. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients

    PubMed Central

    Wagner, U; Marth, C; Largillier, R; Kaern, J; Brown, C; Heywood, M; Bonaventura, T; Vergote, I; Piccirillo, M C; Fossati, R; Gebski, V; Lauraine, E P

    2012-01-01

    Background: The CALYPSO phase III trial compared CD (carboplatin-pegylated liposomal doxorubicin (PLD)) with CP (carboplatin-paclitaxel) in patients with platinum-sensitive recurrent ovarian cancer (ROC). Overall survival (OS) data are now mature. Methods: Women with ROC relapsing >6 months after first- or second-line therapy were randomised to CD or CP for six cycles in this international, open-label, non-inferiority trial. The primary endpoint was progression-free survival. The OS analysis is presented here. Results: A total of 976 patients were randomised (467 to CD and 509 to CP). With a median follow-up of 49 months, no statistically significant difference was observed between arms in OS (hazard ratio=0.99 (95% confidence interval 0.85, 1.16); log-rank P=0.94). Median survival times were 30.7 months (CD) and 33.0 months (CP). No statistically significant difference in OS was observed between arms in predetermined subgroups according to age, body mass index, treatment-free interval, measurable disease, number of lines of prior chemotherapy, or performance status. Post-study cross-over was imbalanced between arms, with a greater proportion of patients randomised to CP receiving post-study PLD (68%) than patients randomised to CD receiving post-study paclitaxel (43% P<0.001). Conclusion: Carboplatin-PLD led to delayed progression and similar OS compared with carboplatin-paclitaxel in platinum-sensitive ROC. PMID:22836511

  18. Changes in Sexual Function in Benign Prostatic Hyperplasia Patients Taking Dutasteride: 1-Year Follow-Up Results

    PubMed Central

    Chi, Byung Hoon

    2011-01-01

    Purpose Sexual adverse events (AEs), a major cause for discontinuing 5α-reductase inhibitor (5ARI) therapy for benign prostatic hyperplasia (BPH), are known to occur most frequently early in therapy and appear to decline over time. The aim of this study was to investigate the changes in sexual function occurring with dutasteride treatment during a 1-year follow-up period in Korean men. Materials and Methods Using the International Index of Erectile Function, we prospectively evaluated, after 1, 3, 6, 9, and 12 months of treatment, the changes in sexual function of 55 outpatients (mean age 62.3±7.2 years) with BPH (mean volume 48.9±16.0 g) who had relatively good erectile function (EF) and were treated with dutasteride for at least 1 year. Results EF scores showed the most significant decrease at 1 month (p<0.01). Function gradually recovered thereafter but was still significantly decreased after 12 months of treatment (p<0.05). The scores for orgasmic function and sexual desire also showed the most significant reduction at 1 month but were restored to the baseline level at 6 months. No significant correlation was observed between changes in sexual function and prostate-specific antigen level, prostate volume, or International Prostate Symptom Scores. Conclusions After 1 month of treatment, dutasteride therapy resulted in a significant reduction in all investigated sexual functions. Overall, recovery in sexual function was noted at 3 months, and orgasmic function and sexual desire were restored to baseline levels at 6 months. However, EF was still significantly reduced at 12 months. PMID:22025960

  19. Diet in 1-year-old farm and control children and allergy development: results from the FARMFLORA birth cohort

    PubMed Central

    Jonsson, Karin; Green, My; Barman, Malin; Sjöberg, Agneta; Brekke, Hilde K.; Wold, Agnes E.; Sandberg, Ann-Sofie

    2016-01-01

    Background A farming environment confers strong protection against allergy development. We have previously shown that farming mothers consume more full-fat dairy than control mothers, who instead consume more low-fat dairy, margarine, and oils; margarine and oil intake was associated with increased risk of allergy development in their children. Objectives The aims of this study were to investigate the differences in diet between children in farming and control families at 1 year of age, to investigate the relation between the diets of the mothers and their children, and to relate the children's diet to allergy development. Design The diet of 1-year-old children from dairy farming families (n=28) and from control families in the same rural area (n=37) was assessed by 24-h dietary recalls, followed by 24-h food diaries. Allergy was diagnosed by pediatricians at 3 years of age using strict predefined criteria. Results Farm children had a higher intake of farm milk, whole cream, cholesterol, saturated fat, and fat in total and tended to eat more butter, while controls consumed more carbohydrates and poultry and tended to eat more margarine. Farm children also had higher intakes of homemade porridge/gruel, oily fish, and iodine. The intake of butter and whole milk in children and mothers correlated significantly in farm families but not in controls. A weak negative association was found between seafood intake and allergy development, while allergy was positively associated with the intake of pork as well as zinc in the control group; these intakes also correlated with each other. Conclusions Consistent with mothers in farming families, the children consumed more full-fat dairy and saturated fat than did controls, but this could not be linked to the low risk of allergy in the farming group. Seafood intake might protect against allergy development, in accordance with earlier findings. PMID:27534847

  20. A longitudinal study on the osteoarthritic change of the temporomandibular joint based on 1-year follow-up computed tomography.

    PubMed

    Lee, Jeong-Yun; Kim, Dae-Jung; Lee, Sang-Goo; Chung, Jin-Woo

    2012-12-01

    This study aims to report the results of a 1-year computed tomographic (CT) follow up of 54 temporomandibular joints (TMJs) affected by osteoarthritis (OA) and to provide longitudinal information on changes in OA and its relationship with clinical signs and symptoms. TMJ OA was diagnosed by history, clinical and CT examinations. The second CT examination was done after about 1 year of conservative treatment. Joints were divided into three groups labeled as no change, improved CT, and worsened CT groups depending on the longitudinal bony change of OA observed in the CT. The sex distribution, mean age, joint noise, subjective pain, joint tenderness, masticatory muscle tenderness, and improvement of subjective symptoms were not different between the groups at the first and second examination, while maximum (p < 0.01) and painless mouth opening range (p < 0.001) at the first examination were both smaller in the worsened CT group. Although the clinical signs and symptoms of OA were improved in 40 joints, 74.1%, at 7.2 ± 4.6 months, the amount if improvement did not differ between the groups. The extent of the destructive change of the condyle was highest in the improved CT group at the first (p < 0.001) and in the worsened CT group at the second examination (p < 0.001). These results imply that the prognosis of OA changes may be independent of the clinical signs and symptoms. More specific longitudinal information as regards OA changes of the TMJ based on a larger sample and a longer follow-up period would be likely to provide a better understanding of TMJ OA. PMID:22075324

  1. Axial length, refraction, and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for retinopathy of prematurity

    PubMed Central

    Lin, Chun-Ju; Tsai, Yi-Yu

    2016-01-01

    Purpose The purpose of this study was to report on the axial length, refraction, and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for threshold retinopathy of prematurity. Methods The authors conducted a comparative, consecutive, original study. Results Twenty-five eyes of 13 patients with threshold retinopathy of prematurity received one intravitreal ranibizumab treatment, and 15 eyes of eight patients received one intravitreal bevacizumab treatment. In the ranibizumab group, the mean gestational age was 26.15±2.08 weeks, with a mean birth weight of 811.15±287.3 g. In the bevacizumab group, the mean gestational age was 26.50±2.14 weeks, with a mean birth weight of 938.38±200.4 g. The mean axial length was 20.34±0.97 mm and the mean spherical equivalent was 0.46±1.36 D in the ranibizumab group, with complete vascularization in 15 of 25 (60%) eyes. The mean axial length was 20.91±1.54 mm and the mean spherical equivalent was −0.60±3.86 D in the bevacizumab group, with complete vascularization in seven of 15 (46.7%) eyes. Conclusion There were no significant differences in the axial length and refraction between children with threshold retinopathy of prematurity who received intravitreal bevacizumab compared to those who received ranibizumab after 1 year of follow-up. It appeared that the ranibizumab treatment could achieve more complete retinal vascularization than the bevacizumab treatment; however, there was no statistical significance and long-term follow-up is needed. PMID:27499611

  2. Single Versus Multi-visit Endodontic Treatment of Teeth with Apical Periodontitis: An in vivo Study with 1-year Evaluation

    PubMed Central

    Gill, GS; Bhuyan, AC; Kalita, C; Das, L; Kataki, R; Bhuyan, D

    2016-01-01

    Background: Apical periodontitis (AP) is one of the most prevalent diseases of the teeth. Treatment of AP is based on the removal of the cause, i.e., bacteria from the root canals. Achievement of adequate bacterial eradication in one appointment treatment remains a controversy. Aim: This prospective study was conducted with the objective to compare the periapical healing of teeth with AP treated in (a) single visit versus (b) two visits, either with or without Vitapex as an intracanal medicament. Subjects and Methods: Patients were selected randomly from the Department of Conservative Dentistry and Endodontics. Forty-three patients (81 teeth) met the inclusion criteria, i.e., AP (both symptomatic and asymptomatic) visible radiographically size ≥2 mm × 2 mm, not suffering from any immune-compromising disease, age between 16 and 65 years and tooth not accessed previously. Patients were randomly divided into three groups, i.e., single-visit group (Group 1), multi-visit group without any intracanal medicament (Group 2), and multi-visit group with Vitapex as interim intracanal medicament (Group 3). Comparison was done radiographically using periapical index (PAI). The primary outcome measure was the change in periapical radiolucency after 1 year assessed by PAI scores. The Mann-Whitney U-test was used to evaluate differences between groups at baseline (immediate postoperative) and at the 12-month follow-up evaluation. Change in PAI score for each group from baseline to 12-month follow-up evaluation was tested with the Wilcoxon signed rank test. The secondary outcome measures, proportion of teeth in each group that could be considered improved (decreased PAI score) or healed (PAI <2), were assessed with the Chi-square test. Results: No statistically significant difference in periapical healing was found between three groups. Conclusion: After 1-year evaluation, no difference in periapical healing was found between single-visit treatment and multi-visit treatment

  3. Long-Term Predictors of Clinical Events after Off-Label Use of Drug-Eluting Stent beyond 1 Year

    PubMed Central

    Ko, Jum Suk; Rhee, Sang Jae; Lee, Eun Mi; Yoo, Nam Jin; Kim, Nam-Ho; Oh, Seok Kyu; Jeong, Jin-Won

    2013-01-01

    Background and Objectives We evaluated the long-term outcomes and predictors of clinical events after off-label use of drug-eluting stents (DES) beyond 1 year after procedure. Subjects and Methods A total of 518 patients who underwent DES implantation for off-label indications and did not have any major adverse cardiac events (MACE) during the first year were analyzed. The occurrence of MACE, including cardiac death, myocardial infarction (MI), stent thrombosis and target vessel revascularization, were evaluated for a median 1179 days (interquartile range 769-1541) after the first year. Results Major adverse cardiac events occurred in 43 patients (8.3%) including 8 cases (1.5%) of cardiac death, 9 cases (1.7%) of MI, 24 cases (4.6%) of target vessel revascularization, and 11 cases (2.1%) of stent thrombosis. Patients with MACE had a higher serum creatinine level, higher incidence of in-stent restenosis lesion, more overlapping stents, a greater number of stents, and longer stents than did patients without MACE. Multivariate analysis revealed that serum creatinine level >1.5 mg/dL {hazard ratio (HR) 2.3, p=0.019}, stent length >33 mm (HR 2.4, p=0.035), and in-stent restenosis lesions (HR 2.4, p=0.040) were independent risk factors for MACE. Patients with DES length >33 mm had a higher incidence of MACE than those with DES length ≤33 mm (HR 2.7, log rank p=0.002). Conclusion The risk of stent thrombosis and target vessel revascularization persisted in patients undergoing off-label DES implantation beyond 1-year follow-up. A total DES length >33 mm was a significant procedural predictor associated with the incidence of MACE. PMID:23613692

  4. A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA)

    PubMed Central

    Porter, John B.; Piga, Antonio; Lai, Yongrong; El-Beshlawy, Amal; Belhoul, Khawla M.; Elalfy, Mohsen; Yesilipek, Akif; Kilinç, Yurdanur; Lawniczek, Tomasz; Habr, Dany; Weisskopf, Marianne; Zhang, Yiyun; Aydinok, Yesim

    2014-01-01

    Randomized comparison data on the efficacy and safety of deferasirox for myocardial iron removal in transfusion dependent patients are lacking. CORDELIA was a prospective, randomized comparison of deferasirox (target dose 40 mg/kg per day) vs subcutaneous deferoxamine (50-60 mg/kg per day for 5-7 days/week) for myocardial iron removal in 197 β-thalassemia major patients with myocardial siderosis (T2* 6-20 milliseconds) and no signs of cardiac dysfunction (mean age, 19.8 years). Primary objective was to demonstrate noninferiority of deferasirox for myocardial iron removal, assessed by changes in myocardial T2* after 1 year using a per-protocol analysis. Geometric mean (Gmean) myocardial T2* improved with deferasirox from 11.2 milliseconds at baseline to 12.6 milliseconds at 1 year (Gmeans ratio, 1.12) and with deferoxamine (11.6 milliseconds to 12.3 milliseconds; Gmeans ratio, 1.07). The between-arm Gmeans ratio was 1.056 (95% confidence interval [CI], 0.998, 1.133). The lower 95% CI boundary was greater than the prespecified margin of 0.9, establishing noninferiority of deferasirox vs deferoxamine (P = .057 for superiority of deferasirox). Left ventricular ejection fraction remained stable in both arms. Frequency of drug-related adverse events was comparable between deferasirox (35.4%) and deferoxamine (30.8%). CORDELIA demonstrated the noninferiority of deferasirox compared with deferoxamine for myocardial iron removal. This trial is registered at www.clinicaltrials.gov as #NCT00600938. PMID:24385534

  5. A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA).

    PubMed

    Pennell, Dudley J; Porter, John B; Piga, Antonio; Lai, Yongrong; El-Beshlawy, Amal; Belhoul, Khawla M; Elalfy, Mohsen; Yesilipek, Akif; Kilinç, Yurdanur; Lawniczek, Tomasz; Habr, Dany; Weisskopf, Marianne; Zhang, Yiyun; Aydinok, Yesim

    2014-03-01

    Randomized comparison data on the efficacy and safety of deferasirox for myocardial iron removal in transfusion dependent patients are lacking. CORDELIA was a prospective, randomized comparison of deferasirox (target dose 40 mg/kg per day) vs subcutaneous deferoxamine (50-60 mg/kg per day for 5-7 days/week) for myocardial iron removal in 197 β-thalassemia major patients with myocardial siderosis (T2* 6-20 milliseconds) and no signs of cardiac dysfunction (mean age, 19.8 years). Primary objective was to demonstrate noninferiority of deferasirox for myocardial iron removal, assessed by changes in myocardial T2* after 1 year using a per-protocol analysis. Geometric mean (Gmean) myocardial T2* improved with deferasirox from 11.2 milliseconds at baseline to 12.6 milliseconds at 1 year (Gmeans ratio, 1.12) and with deferoxamine (11.6 milliseconds to 12.3 milliseconds; Gmeans ratio, 1.07). The between-arm Gmeans ratio was 1.056 (95% confidence interval [CI], 0.998, 1.133). The lower 95% CI boundary was greater than the prespecified margin of 0.9, establishing noninferiority of deferasirox vs deferoxamine (P = .057 for superiority of deferasirox). Left ventricular ejection fraction remained stable in both arms. Frequency of drug-related adverse events was comparable between deferasirox (35.4%) and deferoxamine (30.8%). CORDELIA demonstrated the noninferiority of deferasirox compared with deferoxamine for myocardial iron removal. This trial is registered at www.clinicaltrials.gov as #NCT00600938. PMID:24385534

  6. Artificial neural network models for predicting 1-year mortality in elderly patients with intertrochanteric fractures in China

    PubMed Central

    Shi, L.; Wang, X.C.; Wang, Y.S.

    2013-01-01

    The mortality rate of older patients with intertrochanteric fractures has been increasing with the aging of populations in China. The purpose of this study was: 1) to develop an artificial neural network (ANN) using clinical information to predict the 1-year mortality of elderly patients with intertrochanteric fractures, and 2) to compare the ANN's predictive ability with that of logistic regression models. The ANN model was tested against actual outcomes of an intertrochanteric femoral fracture database in China. The ANN model was generated with eight clinical inputs and a single output. ANN's performance was compared with a logistic regression model created with the same inputs in terms of accuracy, sensitivity, specificity, and discriminability. The study population was composed of 2150 patients (679 males and 1471 females): 1432 in the training group and 718 new patients in the testing group. The ANN model that had eight neurons in the hidden layer had the highest accuracies among the four ANN models: 92.46 and 85.79% in both training and testing datasets, respectively. The areas under the receiver operating characteristic curves of the automatically selected ANN model for both datasets were 0.901 (95%CI=0.814-0.988) and 0.869 (95%CI=0.748-0.990), higher than the 0.745 (95%CI=0.612-0.879) and 0.728 (95%CI=0.595-0.862) of the logistic regression model. The ANN model can be used for predicting 1-year mortality in elderly patients with intertrochanteric fractures. It outperformed a logistic regression on multiple performance measures when given the same variables. PMID:24270906

  7. A comparison of outcome of medical and surgical treatment of migraine headache: In 1 year follow-up

    PubMed Central

    Omranifard, Mahmood; Abdali, Hossein; Ardakani, Mehdi Rasti; Talebianfar, Mohsen

    2016-01-01

    Background: This study was designed to compare the efficacy of the medical treatment versus the surgical treatment approach to decompression of trigger point nerves in patients with migraine headaches. Materials and Methods: Fifty volunteers were randomly assigned to the medical treatment group (n = 25) or the surgical treatment group (n = 25) after examination by the team neurologist to ensure a diagnosis of migraine headache. All patients received botulinum toxin type A to confirm the trigger sites. The surgical treatment group underwent surgical deactivation of the trigger site(s). The medical treatment group underwent prophylactic pharmacologic interventions by the neurologist. Pretreatment and 12-month posttreatment migraine headache frequency, duration, and intensity were analyzed and compared to determine the success of the treatments. Results: Nineteen of the 25 patients (76%) in the surgical treatment group and 10 of the 25 patients (40%) in the medical treatment group experienced a successful outcome (at least a 50% decrease in migraine frequency, duration, or intensity) after 1 year from surgery. Surgical treatment had a significantly higher success rate than medical treatment (P < 0.001). Nine patients (36%) in the surgical treatment group and one patient (4%) in the medical treatment group experienced cessation of migraine headaches. The elimination rate was significantly higher in the surgical treatment group than in the medical treatment group (P < 0.001). Conclusions: Based on the 1-year follow-up data, there is strong evidence that surgical manipulation of one or more migraine trigger sites can successfully eliminate or reduce the frequency, duration, and intensity of migraine headaches in a lasting manner. PMID:27563631

  8. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10

    PubMed Central

    Elwood, J. Mark; Aye, Phyu Sin; Tin Tin, Sandar

    2016-01-01

    New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000–05 and 2006–10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women) in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia. PMID:26938056

  9. Metaplastic Breast Carcinoma Versus Triple-Negative Breast Cancer: Survival and Response to Treatment.

    PubMed

    Aydiner, Adnan; Sen, Fatma; Tambas, Makbule; Ciftci, Rumeysa; Eralp, Yesim; Saip, Pinar; Karanlik, Hasan; Fayda, Merdan; Kucucuk, Seden; Onder, Semen; Yavuz, Ekrem; Muslumanoglu, Mahmut; Igci, Abdullah

    2015-12-01

    Metaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ± 9% vs. 82 ± 6%, P = 0.013) and overall survival (OS) (68 ± 8% vs. 94 ± 4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required. PMID:26717372

  10. The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

    PubMed Central

    Kamieniak, Marta M.; Muñoz-Repeto, Ivan; Borrego, Salud; Hernando, Susana; Hernández-Agudo, Elena; Heredia Soto, Victoria; Márquez-Rodas, Ivan; Echarri, María José; Lacambra-Calvet, Carmen; Sáez, Raquel; Redondo, Andrés; Benítez, Javier

    2016-01-01

    Objective We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. Methods In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients’ survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Results Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. Conclusion Low

  11. 41 CFR 302-2.11 - May the 1-year time limitation for completing all aspects of a relocation be extended?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false May the 1-year time... and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES INTRODUCTION 2-EMPLOYEES ELIGIBILITY REQUIREMENTS General Rules Time Limits § 302-2.11 May the 1-year time limitation...

  12. Survival of auditory hair cells.

    PubMed

    Seymour, Michelle L; Pereira, Fred A

    2015-07-01

    The inability of mammals to regenerate auditory hair cells creates a pressing need to understand the means of enhancing hair cell survival following insult or injury. Hair cells are easily damaged by noise exposure, by ototoxic medications and as a consequence of aging processes, all of which lead to progressive and permanent hearing impairment as hair cells are lost. Significant efforts have been invested in designing strategies to prevent this damage from occurring since permanent hearing loss has a profound impact on communication and quality of life for patients. In this mini-review, we discuss recent progress in the use of antioxidants, anti-inflammatories and apoptosis inhibitors to enhance hair cell survival. We conclude by clarifying the distinction between protection and rescue strategies and by highlighting important areas of future research. PMID:25743696

  13. Dispersion as a Survival Strategy

    NASA Astrophysics Data System (ADS)

    Junior, Valdivino Vargas; Machado, Fábio Prates; Roldán-Correa, Alejandro

    2016-08-01

    We consider stochastic growth models to represent population subject to catastrophes. We analyze the subject from different set ups considering or not spatial restrictions, whether dispersion is a good strategy to increase the population viability. We find out it strongly depends on the effect of a catastrophic event, the spatial constraints of the environment and the probability that each exposed individual survives when a disaster strikes.

  14. Dispersion as a Survival Strategy

    NASA Astrophysics Data System (ADS)

    Junior, Valdivino Vargas; Machado, Fábio Prates; Roldán-Correa, Alejandro

    2016-06-01

    We consider stochastic growth models to represent population subject to catastrophes. We analyze the subject from different set ups considering or not spatial restrictions, whether dispersion is a good strategy to increase the population viability. We find out it strongly depends on the effect of a catastrophic event, the spatial constraints of the environment and the probability that each exposed individual survives when a disaster strikes.

  15. Does Random Dispersion Help Survival?

    NASA Astrophysics Data System (ADS)

    Schinazi, Rinaldo B.

    2015-04-01

    Many species live in colonies that prosper for a while and then collapse. After the collapse the colony survivors disperse randomly and found new colonies that may or may not make it depending on the new environment they find. We use birth and death chains in random environments to model such a population and to argue that random dispersion is a superior strategy for survival.

  16. Surviving gas expulsion with substructure

    NASA Astrophysics Data System (ADS)

    Lee, Paweł L.; Goodwin, Simon P.

    2016-08-01

    We investigate the reaction of clumpy stellar distributions to gas expulsion. We show that regions containing highly unbound substructures/subclusters after gas expulsion can produce a significant final bound cluster. The key quantity in determining if a region is able to form a bound cluster is the global virial ratio, and so regions must be looked at as a whole rather than by an individual substructure/subclusters, when determining if they might survive as a bound cluster.

  17. Proline Mechanisms of Stress Survival

    PubMed Central

    Liang, Xinwen; Zhang, Lu; Natarajan, Sathish Kumar

    2013-01-01

    Abstract Significance: The imino acid proline is utilized by different organisms to offset cellular imbalances caused by environmental stress. The wide use in nature of proline as a stress adaptor molecule indicates that proline has a fundamental biological role in stress response. Understanding the mechanisms by which proline enhances abiotic/biotic stress response will facilitate agricultural crop research and improve human health. Recent Advances: It is now recognized that proline metabolism propels cellular signaling processes that promote cellular apoptosis or survival. Studies have shown that proline metabolism influences signaling pathways by increasing reactive oxygen species (ROS) formation in the mitochondria via the electron transport chain. Enhanced ROS production due to proline metabolism has been implicated in the hypersensitive response in plants, lifespan extension in worms, and apoptosis, tumor suppression, and cell survival in animals. Critical Issues: The ability of proline to influence disparate cellular outcomes may be governed by ROS levels generated in the mitochondria. Defining the threshold at which proline metabolic enzyme expression switches from inducing survival pathways to cellular apoptosis would provide molecular insights into cellular redox regulation by proline. Are ROS the only mediators of proline metabolic signaling or are other factors involved? Future Directions: New evidence suggests that proline biosynthesis enzymes interact with redox proteins such as thioredoxin. An important future pursuit will be to identify other interacting partners of proline metabolic enzymes to uncover novel regulatory and signaling networks of cellular stress response. Antioxid. Redox Signal. 19, 998–1011. PMID:23581681

  18. Demonstration of survivable space penetrator

    NASA Astrophysics Data System (ADS)

    Church, Philip; Huntington-Thresher, William; Bruce, Alan; Penny, Nick; Smith, Alan; Gowan, Rob

    2012-03-01

    This work was performed in support of MoonLITE which is a proposed UK space mission to the moon. The basic premise is to deploy 4 instrumented penetrators, one each on the near-side, farside and at the poles of the moon, with an impact velocity of approximately 300m/s. The primary science aims are to set up a passive seismometer network, investigate the presence of water and volatiles and determine thermal gradients in the lunar soil (i.e. regolith). A key requirement is that the penetrator shell survives the impact together with the instrument payload and supporting subsystems. The material chosen for the penetrator shell was 7075 aluminium alloy, which is a good compromise between high compressive strength and low mass. The baseline penetrator design was evaluated and refined using the DYNA3D hydrocode to determine the survivability of the penetrator in sand at an impact velocity of 300m/s and an attack angle of 8°. The simulations predicted that the penetrator design would survive this severe impact condition which was confirmed by experiments on the Pendine rocket test track.

  19. Conditional disease-free survival after liver transplantation for hepatocellular carcinoma

    PubMed Central

    Dong, Jian; Zhu, Ying; Ma, Feng; Ren, Yifang; Lu, Jianwen; Wang, Zhengxin; Qin, Lunxiu; Wu, Rongqian; Lv, Yi

    2016-01-01

    Abstract Traditionally, survival estimates following liver transplantation (LT) of hepatocellular carcinoma (HCC) patients were calculated as survival from the surgery date, but future survival probabilities can change over time and conditional disease-free survival (CDFS) may provide patients and clinicians with more accurate prognostic information. This study aimed to assess CDFS in HCC patients after LT. Three hundred eighty-four HCC patients who underwent LT were included. Disease-free survival (DFS) was calculated using the Kaplan–Meier analysis. The 3-year CDFS, which represents the probability of remaining disease free for an additional 3 years, was calculated. 1-, 3-, and 5-year DFS rates after LT were 69.9%, 45.8%, and 39.0 %, respectively. Based on the concept of CDFS, the probability of surviving an additional 3 years given that the patient was disease free at 1 year, 3 years, and 5 years were 58.4%, 76.9%, and 83.1%, respectively. Multivariate analysis indicated that larger tumor size (hazard ratio [HR], 1.509; 95% CI, 1.146–1.985; P = 0.003) was associated with poorer DFS. Patients with worse prognostic features at baseline demonstrated the greater increase in CDFS over time. Survival estimates following liver transplantation of HCC patients change according to survival time accrued since surgery. CDFS estimates improved dramatically over time especially among patients with worse prognostic features at the time of surgery. CDFS may be a useful tool in counseling patients with HCC, as it is a more accurate assessment of future survival for those patients who have already survived a certain amount of time. PMID:27495049

  20. Within- and Between-Child Variation in Repeated Urinary Pesticide Metabolite Measurements over a 1-Year Period

    PubMed Central

    Hughes, Michael D.; Spengler, John D.; Lu, Chensheng

    2013-01-01

    Background: Children are exposed to pesticides from many sources and routes, including dietary and incidental ingestion, dermal absorption, and inhalation. Linking health outcomes to these exposures using urinary metabolites requires understanding temporal variability within subjects to avoid exposure misclassification. Objectives: We characterized the within- and between-child variability of urinary organophosphorus and pyrethroid metabolites in 23 participants of the Children’s Pesticide Exposure Study–Washington over 1 year and examined the ability of one to four spot urine samples to categorize mean exposures. Methods: Each child provided urine samples twice daily over 7- to 16-day sessions in four seasons in 2003 and 2004. Samples were analyzed for five pyrethroid and five organophosphorus (OP) metabolites. After adjusting for specific gravity, we used a customized maximum likelihood estimation linear mixed-effects model that accounted for values below the limit of detection to calculate intraclass correlation coefficients (ICC) and conducted surrogate category analyses. Results: Within-child variability was 2–11 times greater than between-child variability. When restricted to samples collected during a single season, ICCs were higher in the fall, winter, and spring than in summer for OPs, and higher in summer and winter for pyrethroids, indicating an increase in between-person variability relative to within-person variability during these seasons. Surrogate category analyses demonstrated that a single spot urine sample did not categorize metabolite concentrations well, and that four or more samples would be needed to categorize children into quartiles consistently. Conclusions: Urinary biomarkers of these short half-life pesticides exhibited substantial within-person variability in children observed over four seasons. Researchers investigating pesticides and health outcomes in children may need repeated biomarker measurements to derive accurate

  1. The reciprocal relationship between executive function and theory of mind in middle childhood: a 1-year longitudinal perspective

    PubMed Central

    Austin, Gina; Groppe, Karoline; Elsner, Birgit

    2014-01-01

    There is robust evidence showing a link between executive function (EF) and theory of mind (ToM) in 3- to 5-year-olds. However, it is unclear whether this relationship extends to middle childhood. In addition, there has been much discussion about the nature of this relationship. Whereas some authors claim that ToM is needed for EF, others argue that ToM requires EF. To date, however, studies examining the longitudinal relationship between distinct subcomponents of EF [i.e., attention shifting, working memory (WM) updating, inhibition] and ToM in middle childhood are rare. The present study examined (1) the relationship between three EF subcomponents (attention shifting, WM updating, inhibition) and ToM in middle childhood, and (2) the longitudinal reciprocal relationships between the EF subcomponents and ToM across a 1-year period. EF and ToM measures were assessed experimentally in a sample of 1,657 children (aged 6–11 years) at time point one (t1) and 1 year later at time point two (t2). Results showed that the concurrent relationships between all three EF subcomponents and ToM pertained in middle childhood at t1 and t2, respectively, even when age, gender, and fluid intelligence were partialled out. Moreover, cross-lagged structural equation modeling (again, controlling for age, gender, and fluid intelligence, as well as for the earlier levels of the target variables), revealed partial support for the view that early ToM predicts later EF, but stronger evidence for the assumption that early EF predicts later ToM. The latter was found for attention shifting and WM updating, but not for inhibition. This reveals the importance of studying the exact interplay of ToM and EF across childhood development, especially with regard to different EF subcomponents. Most likely, understanding others’ mental states at different levels of perspective-taking requires specific EF subcomponents, suggesting developmental change in the relations between EF and ToM across

  2. Survival and Symptom Relief after Palliative Radiotherapy for Esophageal Cancer

    PubMed Central

    Welsch, Julia; Kup, Philipp Günther; Nieder, Carsten; Khosrawipour, Veria; Bühler, Helmut; Adamietz, Irenäus A.; Fakhrian, Khashayar

    2016-01-01

    Purpose: The aim of this study was to assess the 6-months dysphagia-free survival, improvement in swallowing function, complication rate, and overall survival in patients with incurable esophageal cancer treated with palliative radiotherapy. Methods: We retrospectively reviewed data from 139 patients (median age 72 years) with advanced/recurrent incurable esophageal cancer, who were referred to 3 German radiation oncology centers for palliative radiotherapy between 1994 and 2014. Radiotherapy consisted of external beam radiotherapy (EBRT) with 30 - 40.5 Gy/2.5 - 3 Gy per fraction, brachytherapy alone (BT) with 15 - 25 Gy/5 - 7Gy per fraction/weekly and EBRT + BT (30 - 40.5 Gy plus 10 - 14 Gy with BT) in 65, 46, and 28 patients, respectively. Dysphagia-free survival (Dy-PFS) was defined as the time to worsening of dysphagia for at least one point, a new loco-regional failure or death of any cause. Results: Median follow-up time was 6 months (range 1-6 months). Subjective symptom relief was achieved in 72 % of patients with median response duration of 5 months. The 1-year survival rate was 30%. The 6-months Dy-PFS time for the whole group was 73 ± 4%. The 6-months Dy-PFS was 90 ± 4% after EBRT, 92 ± 5% after EBRT + BT and 37 ± 7% after BT, respectively (p<0.001). Five patients lived for more than 2 years, all of them were treated with EBRT ± BT. Ulceration, fistula and stricture developed in 3, 6 and 7 patients, respectively. Conclusions: Radiotherapy leads to symptom improvement in the majority of patients with advanced incurable esophageal cancer. The present results favor EBRT ± BT over BT alone. Due to the retrospective nature of this study, imbalances in baseline characteristics might have contributed to this finding, and further trials appear necessary. PMID:26819634

  3. Visceral adipose tissue is prognostic for survival of diffuse large B cell lymphoma treated with frontline R-CHOP.

    PubMed

    Shin, Dong-Yeop; Kim, Areumnuri; Byun, Byung Hyun; Moon, Hansol; Kim, Soyeun; Ko, Young-Jin; Kim, Min-Jung; Lee, Hyo-Rak; Kang, Hye-Jin; Na, Im Il; Park, Sunhoo; Lee, Seung Sook; Yang, Sung-Hyun

    2016-02-01

    The potential role of visceral adipose tissue (VAT) as a prognostic factor in patients with diffuse large B cell lymphoma (DLBCL) treated with frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy was explored. Total adipose tissue and VAT were measured by analyzing positron emission tomography (PET)/computed tomography (CT) images obtained during the initial staging of patients with DLBCL. The VAT ratio was calculated as follows: VAT ratio = VAT area/total adipose tissue area. Body mass index (BMI), sex, and International Prognostic Index (IPI) were also incorporated as co-variates in the final model of multivariate Cox regression analysis for survival. A total of 156 patients with DLBCL, who were treated with frontline R-CHOP, were enrolled in our study. The